Breast Cancer Survivors

Chemo Secrets From a Breast Cancer Survivor

Undergoing chemotherapy can be one of the most terrifying things that you go through in your life. One of the most frightening things about chemotherapy is the lack of real information that most people have about it, and the unknown makes it so much more frightening as a result. This eBook, written by a young cancer survivor gives you the real story about what chemo is all about. The most valuable information you can get about chemotherapy is from someone that has already experienced it. This PDF eBook allows you to download and read it as soon as your order it. You can begin your journey of reassurance as soon as you want! Because that's what this is about: chemo does not have to be a terrifying unknown! Other people have gone through it before, and want to help you through it as well! This eBook is the guide through chemo that many people wish they could have had, and now you can have it yourself! More here...

Chemo Secrets From a Breast Cancer Survivor Overview

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Author: Nalie Augustin
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Recently several visitors of websites have asked me about this book, which is being promoted quite widely across the Internet. So I ordered a copy myself to figure out what all the publicity was about.

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Systemic Chemotherapy General Pharmacologic Principles

For chemotherapy to be effective, it must be delivered to sensitive tumor cells in adequate concentrations. For nervous system tumors, as with all neoplasms, choosing appropriate chemotherapy administration routes and schedules is important in achieving adequate concentrations. In addition, CNS tumors have unique features, such as the blood-brain and blood-tumor barriers, that affect chemotherapeutic options. Systemic chemotherapy may be given orally or intravenously. Oral bioavailability is important in deciding which route is more appropriate. This decision depends on several factors, including stability within gastric acid, absorption through the gastrointestinal tract, hepatic metabolism, biliary excretion, and treatment-related emesis. In addition, determin Physical characteristics unique to the CNS also affect drug concentration within CNS tumors. The blood-brain barrier (BBB) is an important limiting factor.6 The BBB is made up of tight junctions between endothelial cells in...

Local Or Intratumoral Chemotherapy

The preceding discussion has focused on systemic chemotherapy delivery. However, local delivery may be an attractive alternative for patients with CNS tumors.12 These tumors are locally recurrent and rarely spread outside the CNS. Local high-dose chemotherapy without systemic administration may be efficacious but avoid systemic toxicities. Furthermore, local delivery may circumvent the BBB. The pioneering work of Brem and colleagues1 at Johns Hopkins has demonstrated the utility of another technique for intratumoral chemotherapy in malignant gliomas. Biodegradable wafers impregnated with chemotherapeutic agents can be used to line resection cavities after malignant gliomas are removed. This is associated with modestly prolonged sur-vival.1,15 As a result, these wafers have recently been approved by the Food and Drug Administration (FDA) for the treatment of both recurrent and newly diagnosed malignant gliomas. Finally, convection-enhanced delivery (CED) utilizes catheters placed...

Other Combination Chemotherapy Trials

Phase II studies of this combination indicate high levels of activity in various tumors, but none of these studies were randomized, so their interpretation is difficult (74). A Phase III study using this combination as first-line chemotherapy for patients with extensive disease of SCLC showed a significant improvement

Chemotherapy General Considerations

AAs represent approximately 25 of malignant gliomas. Because they are less common, they typically compose a small part of the study group in clinical trials for malignant gliomas. Misclassification has been problematic as well. In a large phase III trial of PCV chemotherapy with or without BUdR as a radiation sensitizer, 78 of 268 patients enrolled were ineligible primarily on the basis of central pathology review findings, the most common scenario being that tumors classified as anaplastic at the local institutions were upgraded to GBM after central review.96a Patients with AA have a median survival of about 4 years,75 as opposed to approximately 1 year for patients with GBM.89a In general, AAs are more responsive to chemotherapy than are the more malignant forms of gliomas (i.e., the glioblastoma).51 Furthermore, whereas glioblastomas show a 12 to 13 biologic response by imaging criteria,41,1233 AAs show a complete or partial response in 55 of cases in a small series.51 The time of...

Alcohol and Breast Cancer

Although many studies have shown that breast cancer rates are higher among heavier drinkers, a number of research reports suggest that only a small increase in risk begins to appear among women who normally consume just one or two drinks per day. This is not found consistently in all studies. At our institute at Boston University, we have completed a study of wine, beer, and spirits as they relate to breast cancer by using data from the Framingham Study that has been

Chemotherapy Induced Nausea and Vomiting

CINV is classified as (a) acute (occurring within 24 hours after receiving chemotherapy) (b) delayed (occurring more than 24 hours after receiving chemotherapy) or (c) anticipatory (occurring prior to chemotherapy in patients who experienced acute or delayed nausea and vomiting with previous courses).5,43,47 Risk factors for CINV include poor emetic control with prior chemotherapy, female gender, low chronic alcohol intake, and younger age.43, For prevention of acute CINV for patients receiving moderately or highly emetogenic chemotherapy, a combination of antiemetics with different mechanisms of action is recommended (Table 20-4).5'14'43'47 Patients receiving chemotherapeutic agents with low emetogenic potential should receive a corticosteroid as CINV prophylaxis, and those receiving chemotherapy with minimal emetogenic risk do not require prophylaxis. Delayed nausea and vomiting is more difficult to prevent and treat. It occurs most often with cis-platin- and cyclophosphamide-based...

Role of Chemotherapy and Organpreserving Approaches

Although numerous randomized trials have failed to demonstrate any survival benefit for neoadjuvant or sequential chemotherapy schedules, the major spinoff of the neoadjuvant approach was the observation that function of important structures such as the larynx and tongue could be preserved without compromising local control or survival.26 More recently, the radiosensitizing effects of chemotherapy have been exploited in designing concurrent chemoradiation protocols, and 3-year local control rates of 64 percent were achieved at the Memorial Sloan-Kettering Cancer Center (MSKCC) for a subset of patients with oropharyngeal tumors treated with concomitant chemoradiation and delayed accelerated fractiona-tion.27 For the surgeon, there are several considerations in operating on patients who have persistent or residual disease after nonsurgical treatment. Apart from the technical difficulties and risks associated

Chemotherapy and Radiotherapy

Treatment protocols using chemo RT to preserve organ function have successfully demonstrated their ability to anatomically preserve the larynx without compromising survival. One aspect of these protocols that is often underappreciated is the functional capacity of the retained organs. Few investigators have clearly documented the functional sequelae of chemotherapy and radiation therapy. Recently, Lazarus retrospectively studied patients being treated with chemotherapy and radiation therapy and found that 40 percent had swallowing difficulties.36 Clinical evidence of disorders in the pharyngeal phase of swallowing has been demonstrated in patients who have undergone chemotherapy and radiation therapy for tumors of the upper aerodiges-tive tract. Specifically, reduced laryngeal closure, reduced laryngeal elevation and reduced posterior tongue base movement relative to age-matched controls has been documented.36 Certainly, patients who successfully undergo chemo RT treatments to...

Late effects of cisplatinbased chemotherapy

For many patients who have GCT, cisplatin-based chemotherapy is required for cure. Because patients who have GCT are usually young and are likely to become long-term survivors, issues related to long-term complications of this treatment are important. Cisplatin-based chemotherapy for patients who have GCT may be associated with long-term consequences that may affect several organ systems (Box 3). A review concerning the medical management of the long-term GCT survivor has recently been published 19 . The most studied late effect of cisplatin-based chemotherapy in patients who have GCT is cardiovascular risk. Raynaud phenomenon has been reported in patients who have GCT treated with cisplatin-based chemotherapy 20 . Serious vascular complications (eg, myocardial infarction, stroke, thromboembolic disease) have been reported in patients who had GCT treated with cis-platin-based chemotherapy 21-23 . Larger series have examined the risk for cardiovascular events Box 3. Potential late...

Chemotherapy programs in advanced disease

Germ cell tumors (GCT) are considered a model for curable cancer based on the successful treatment of metastatic disease with cisplatin-containing chemotherapy (More than 90 of newly diagnosed GCT patients are cured.) 1 . Accumulated data from phase II and III trials show that treatment with cisplatin, vinblastine, and bleomycin (VAB series, PVB) achieves a durable response in 70 to 80 of patients who have metastatic GCT 2-5 . Treatment-related toxicity was substantial in these regimens, however, including hematologic, gastrointestinal, neurologic, dermatologic, and pulmonary toxicities 3 .

Chemotherapy for Advanced Tumors

In attempts to improve the survival rates and local control of advanced sinonasal tumors, chemotherapy has been administered as an adjuvant treatment in a wide variety of methods. Chemotherapy has been given (1) with radiation and daily tumor debridement,33-36 (2) by topical application,35 (3) selectively to the head and neck through intra-arterial infusion,3337-39 (4) as a neoadjuvant treatment prior to further local treat-ment,40-42 and (5) concomitantly with hyperfraction-ated radiation therapy43-45 (Tables 11-2 and 11-3). Unfortunately, many studies have been published with a wide variety of different chemotherapy agents and treatment regimens, small numbers of patients, short follow-up periods, varying tumor histologies, and varying outcomes, all of which make a universal interpretation of these results difficult. The preliminary data from these studies suggest that advanced stage sinonasal tumors derive a significant benefit from combination chemotherapy regimens and are...

Early trials of adjuvant chemotherapy

Before the advent of cisplatin-based chemotherapy, patients who had completely resected node-positive disease (pN1 and pN2) were offered either no adjuvant chemotherapy, minimally effective chemotherapy, or postoperative radiotherapy 15,16 . The relapse rate in this patient population was 20 to 70 , with most studies showing a relapse rate of 50 to 60 17 . As cisplatin-based chemotherapeutic regimens were found to be effective in stage III GCT, these regimens were studied in the adjuvant setting. The hope was to decrease the proportion of patients who relapsed after RPLND and to increase the proportion of patients who were cured. These early trials of adjuvant chemotherapy are summarized in Table 2. The regimens, which included cisplatin, vinblastine, and bleomycin, were superior to prior trials of non-platinum-based chemotherapy. One non-platinum-containing regimen studied at Memorial Sloan-Kettering Cancer Center (MSKCC) was mini-VAB, which consisted of vinblastine, dactinomycin,...

Chemotherapy with Maxillary Debridement

Chemotherapy has been incorporated into numerous different treatment regimens with varying agents, methods of delivery, and combinations with radiation and or surgery. In the 1970s several groups in Japan began trying a combination of chemotherapy, radiation therapy and routine tumor debridement or cryosurgery within the maxillary sinus. The regimens included 5-fluorouracil (5-FU) or cisplatin with delivery through intravenous,3436 selective intra-arterial,33 and topical methods.35 Responses to these treatments were encouraging. Four- to 5-year survival rates for squamous cell carcinoma were in the 46 to 65 percent range for all histologic types combined (see Table 11 -2). Sakata initially tried a regmen of 5-FU, bromodeoxyuridine, low-dose radiation therapy, and daily tumor d bridement and reported a 5-year survival of 46 percent. Modifications of this regimen without chemotherapy or without daily d bridement led to significantly worse survival. However, the additions of (1)...

Neoadjuvant or Concurrent Chemotherapy

Despite the encouraging results described above, both routine tumor debridement and intra-arterial cannula-tion present technical demands and may not be available for widespread use. Chemotherapy may be administered intravenously as a neoadjuvant agent prior to treatment with other modalities. LoRusso gave 24 patients with stage III or IV disease various chemotherapy combinations, including 5-FU and cisplatin, and followed this with surgery and or radiation therapy. Overall 5-year survival was only 9.5 percent, but 29 percent of patients remained disease free at a median of 15 months.40 Bjork-Eriksson treated 12 patients with 5-FU and cisplatin followed by radiation therapy and then limited surgery. Local control was achieved in 11 patients and 10 remained alive without disease at a mean follow up of 27 months.41 Rosen treated 12 patients with 5-FU and cisplatin followed by surgery and radiation with or without concomittant chemotherapy. Of these 12 patients, 11 had complete responses...

Locally Advanced and Inflammatory Breast Cancer

Current data suggest that patients with advanced stage III disease who are at least T3 (> 5 cm in maximal diameter), T4 (extension to chest wall or skin), or N2 (fixed or matted axillary lymphadenopathy) are best treated with preoperative chemotherapy or hormonal therapy, followed by surgery and then local-regional fractionated radiation therapy. Limited data support the addition of adjuvant chemotherapy or hormonal therapy postoperatively and after radiation therapy. Excellent local control can be achieved in 80 to 90 of women, and approximately 30 of women with stage IIIb disease (direct invasion of skin or chest wall) or inflammatory breast cancer remain free of cancer after 1 year.24,68

Chemotherapy for Brain Metastases

Systemic cytotoxic chemotherapy has not been extensively evaluated in the treatment of patients with brain metastasis. A study published in 1986 showed significant response rates in a fairly heterogeneous group of patients with brain metastases due to breast cancer.107 Approximately 63 of these patients had received prior adjuvant chemotherapy, primarily CMF (cyclophosphamide, methotrexate, and 5-Fu) or cyclophos-phamide and doxorubicin. Response rates, including partial and complete responses, measured approximately 30 to 50 percent. A similar study focusing on breast cancer also demonstrated impressive results.14 Additional studies included other primary sites and have also demonstrated responses using a variety of chemotherapy agents.29'30'56'74'141 Recent reports in mixed patient populations have demonstrated benefit with a newer chemotherapy drug, temozolomide, which is known to obtain adequate levels in the CNS with oral administration, can be given on a chronic basis (years in...

Chemotherapyinduced Nausea and Vomiting

Patients tell me how difficult it is to deal with all the emotions and logistics of chemotherapy, but the nausea and vomiting that often follow are just too much to bear. Your energy level and appetite decline rapidly. Antiemetic (antinausea) medications are available, but they may not work to alleviate the problem completely. According to the National Institute of Health's panel of scientists, researchers, and practitioners, clinical studies on humans have shown acupuncture to be effective for nausea caused by cancer chemotherapy. According to the National Institute of Health's panel of scientists, researchers, and practitioners, clinical studies on humans have shown acupuncture to be effective for nausea caused by cancer chemotherapy. Beth was 44 years of age and undergoing chemotherapy treatments for breast cancer. Dealing with the cancer was hard enough, but the nausea and vomiting from the chemo were beginning to take their toil. She had tried antiemetic medications, but none had...

Rationale for surgery after chemotherapy

The rationale for post-chemotherapy RPLND is based on (1) the established diagnostic role, (2) the therapeutic efficacy of the procedure, (3) the natural history of residual masses, and (4) the decreasing morbidity of these surgical procedures. With regard to the diagnostic role of RPLND, surgical resection after chemotherapy yields one of the following histologic findings (1) pure necrosis or fibrosis, (2) teratoma with or without necrosis fibrosis, (3) viable germ cell carcinoma to any degree, or (4) non-germ cell carcinoma to any degree. The frequencies of these histologies vary in the literature and are summarized in Table 1 3-17 . In general, necrosis fibrosis is found in 50 , teratoma in 35 , and viable germ cell tumor in 15 . The rare finding of non-germ cell elements (ie, malignant transformation) is addressed in another article in this issue. There is no established instrument, parameter, or nomo-gram to accurately predict the histology of the residual mass preoperatively....

Classification of postchemotherapy retroperitoneal lymph node dissection

RPLND constitutes most surgical resection after systemic chemotherapy for advanced testic-ular carcinoma. The Indiana classification of RPLND categorizes different types of RPLND to facilitate assessment of the outcome in this setting 25 . Standard RPLND refers to patients after induction chemotherapy who have disseminated testicular cancer and present with residual radiographic disease in the retroperitoneum and normalized STM. Salvage RPLND refers to cases that are status post second-line salvage chemotherapy (additional courses of cisplatin-based or highdose chemotherapy with bone marrow support) with normalized tumor markers. Desperation RPLND refers to cases that are post-second-line salvage chemotherapy with elevated markers. Redo RPLND refers to surgery for patients who had previous RPLND with in-field recurrence. Unresectable RPLND denotes extensive unresect-able tumor at the time of surgery.

Patient selection and indications for postchemotherapy retroperitoneal lymph node dissection

The current indications for surgery after initial systemic chemotherapy depend on several factors, including (1) histology of primary tumor, (2) the presence and size of residual radiographic masses, and (3) the known distributions and natural history of the various post-chemotherapy mass The approach to residual masses after chemotherapy in the setting of pure seminoma differs substantially from the residual masses in the setting of nonseminomatous GCT (NSGCT) for several reasons. First, the post-chemotherapy seminoma masses tend to be more desmoplastic in nature and consequently are more intimately associated with the great vessels. The result of this desmoplastic response to chemotherapy is an obliteration of tissue planes, more difficult resection, and resulting increased morbidity. second, teratoma is rare in a pure seminoma mass after chemotherapy. The aforementioned dangerous biologic potential of teratoma is thus avoided. Lastly, there is evidence that some post-chemotherapy...

Extent of surgery after chemotherapy

Multiple institutions have examined the role of limited RPLND in the post-chemotherapy setting. Aprikian and colleagues 67 from Memorial Sloan-Kettering Cancer Center studied the use of intraoperative frozen section analysis to dictate the extent of surgery in 40 patients who had met-astatic NSGCT. If frozen section revealed necrosis, then a modified template RPLND was performed however, if teratoma or viable tumor was found, then a bilateral RPLND was attempted. Twenty-one patients (53 ) had necrosis Complicated retroperitoneal lymph node dissection after chemotherapy identified in frozen section analysis of the residual masses, with 18 (85.7 ) confirmed in permanent section. Two patients had microscopic viable germ cell tumor unrecognized on frozen section, and 1 had microscopic teratoma in the residual mass. Of these 21 patients, 3 (14.3 ) experienced recurrences, 2 had germ cell tumors in the chest, and 1 had liver metastasis. The remaining 18 (85.7 ) patients had no evidence of...

Immune system in patients undergoing chemotherapy and radiotherapy

One of the common and most dangerous side effects associated with an intensive course of chemotherapy and or radiotherapy is bone marrow suppression and a reduction in the number of white blood cells (leukocytes) in the blood, a condition called leukopenia (Kubota et al., 2001 Hood, 2003). In particular, febrile neutropenia is a common complication of cancer chemotherapy which can cause death in 4-21 of cancer patients (Young and Feld, 2000 Ray-Coquard et al., 2003). With the advances in genetic engineering, recombinant forms of haematopoietic cytokines, also called CSF, have been generated that stimulate the proliferation and differentiation of different populations of white blood cells, e.g. the human G-CSF filgrastim has been shown to be effective in reducing neutropenia, decreasing its severity and duration, reducing hospital-izations and the incidence of infection, and improving quality of life in patients undergoing chemotherapy (Valley, 2002). A modified version of filgrastim,...

Role of adjuvant chemotherapy

Postoperative chemotherapy appears to improve disease-free recurrence in patients with germ-cell cancer after first-line chemotherapy but not when given after second-line chemotherapy 2 . This lack of benefit in the salvage setting is thought to be secondary to the development of tumor che-moresistance. Persistently elevated serum tumor markers after systemic therapy implies a degree of chemoresistance and in the current series adjuvant chemotherapy did not improve patient survival. In the Albers series of 30 patients with elevated serum tumor markers undergoing surgery, only 6 of the 18 patients with viable cancer in the residual tumor specimen received postoperative chemotherapy, of whom 4 have remained free of disease, 1 died of disease, and 1 has progressive disease 4 . The Royal London Hospital, in their series of 30 patients, cautioned that in ''. managing these patients do not continue indefinitely with chemotherapy in the face of persistently elevated markers and remember that...

Adjuvant Radiation Therapy And Chemotherapy

High-grade gliomas in children have conventionally been treated with maximal resection followed by radiation therapy to the tumor bed and a margin of surrounding brain, with a dosage of 5000 to 6000 cGy in 180 to 200 cGy day fractions. Cooperative group studies have demonstrated that the administration of chemotherapy in addition to irradiation improves the chances for long-term survival, although to date the optimal treatment regimen remains uncertain. In the CCG-943 study, children who were randomly assigned to receive radiation therapy followed by CCNU (lomustine), vincristine, and prednisone (pCV) had a 5-year event-free survival of 46 versus 18 for patients treated with radiation therapy alone.50 In a subsequent study (CCG-945), a more complex eight-drug regimen failed to further improve survival,15 reflecting the low dose intensity of several components of the 8-in-1 regimen. This realization formed the impetus for subsequent studies that have administered more intensive...

Indications for postchemotherapy surgery

Generally accepted indications for postchemo-therapy resection include patients who have residual radiographic disease and normalized serum tumor markers (a-fetoprotein and human chorionic gonadotropin). The added benefit of resection must be weighed against the morbidity of additional surgery. Removal of residual viable cancer offers therapeutic benefit and can be curative in a subset of patients. The excision of residual teratoma is also beneficial because teratoma possesses the potential to undergo malignant transformation, and to continue to grow, obstruct, and invade adjacent structures (growing teratoma syndrome). Because teratomas are chemoresistant, surgical extirpation is the only cure. Unfortunately clinicians cannot reliably predict the histology of residual masses within and outside of the retroper-itoneum. The studies presented above demonstrate a reasonable correlation between retroperitoneal and non-retroperitoneal histology, suggesting that perhaps necrosis discovered...

Chemotherapy for Metastatic Disease

The data on the use of single-agent chemotherapy are limited due to the studies involving small numbers and mixed populations whereby chemotherapy has been administered in different settings and stages of the disease. Small studies have demonstrated modest efficacy of bleomycin, methotrexate, cisplatin, and 5-FU, either as single agents or as combination therapy, as illustrated in Table 12.1.

What is the role of chemotherapy in the treatment of a metastatic spinal lesion

Chemotherapy is used in patients with documented spinal metastases, patients at risk of developing spinal metastases, and patients with spinal lesions not amenable to surgical excision. The response to chemotherapy is determined by the tumor type. Tumors that are highly sensitive to chemotherapy include small-cell carcinoma of the lung, Ewing's sarcoma, thyroid carcinoma, breast carcinoma, lymphoma, germ cell tumors, and neuroblastoma. Tumors that are relatively resistant to chemotherapy include adenocarcinoma of the lung and GI tract, squamous cell carcinoma of the lung, metastatic melanoma, and renal cell carcinoma.

Chemotherapy Administration

Evaluate the chemotherapy regimen to ensure the correct dose and route of administration. 2. Check patient laboratory values to ensure that the CBC and organ function studies are normal prior to administering chemotherapy. 3. If a patient has renal or hepatic impairment or a poor metabolizer genotype, adjust chemotherapy doses if necessary. Monitor patient for other known toxicities of the chemotherapy regimen, and decrease the dose or discontinue the regimen if necessary

Chemotherapyinduced toxicities nausea vomiting

Nausea and vomiting are among the most commonly feared toxicities by patients undergoing chemotherapy. One study demonstrated that both nausea and vomiting ranked in the top five bothersome side effects of chemotherapy.1 The optimal method of managing CINV is to provide adequate pharmacologic prophylaxis given a patient's risk level for emesis. Studies have demonstrated that insufficient control during the first cycle of chemotherapy leads to more difficulty in controlling emesis for subsequent cycles.2

Chemotherapy and Chemoprevention in Head and Neck Cancer

For most epithelial tumors of the head and neck, surgery and or radiation therapy have historically been the principal treatment modalities. Systemic drug therapy alone in most instances does not have curative potential, and previously had been reserved for the palliative treatment of recurrent and or distant metastatic disease. Over the last decade, this has changed dramatically, especially for squamous cell carcinomas of the upper aerodigestive tract, the most common type of invasive malignancy to occur in this body region if skin cancers are excluded. Randomized trials have demonstrated that integrated chemotherapy radiation programs improve disease control rates relative to those obtained with radiation therapy alone in patients with unresectable squamous cell carcinomas of the head and neck,1-4 as well as in those with advanced nasopharyngeal5 and oropharyngeal6 cancers. Combined modality programs including chemotherapy and radiation, with surgery to the primary site reserved for...

Chemotherapy for Salivary Gland Cancers

Major and minor salivary gland cancers represent approximately 5 to 10 percent of head and neck malignancies.134 135 In general, surgery and or radiation have been the principle treatment modalities, with chemotherapy primarily used in the recur-rent metastatic disease setting. As a single modality, chemotherapy is not curative. Because of the relative rarity and heterogeneity of these tumors, the available data on the efficacy of systemic therapy is often of poor quality. Many series are small, are developed in a retrospective manner, and combine different salivary gland cancer subtypes even though drug activity may vary among them.136 Single-agent activity has been shown for doxorubicin, cisplatin, 5-fluorouracil, and selected other drugs.137-142 The minority of patients will have a major response. In general, the response rates associated with combination therapy are higher than those with a single agent. Selected combination regimens are summarized in Table 22-10. The combination...

Antiviral chemotherapy of eczema herpeticum

Systemic antiviral chemotherapy must be given to avoid complications of a disseminated HSV infection such as HSV encephalitis or herpetic keratitis. Currently, the most potent drugs used for HSV therapy are nucleoside analogues which interfere with viral DNA replication. Before the introduction of aciclovir treatment, the mortality rate of EH leading to multiple organ involvement and encephalitis was about 70 .22

Pharmacologic Therapy Chemotherapy

Traditional chemotherapeutic agents interfere with processes during cell division or affect DNA replication in nondividing cells, resulting in cell death. Unfortunately, these agents are not specific for cancer cells, and other tissues in the body often are affected. Rapidly cycling cells, both tumor and normal tissue such as bone marrow, epithelial cells of the GI tract, and hair follicles, are most susceptible to chemotherapy toxicity. Because the dose of traditional chemotherapy agents is determined in phase I studies where the maximum tolerated dose is considered the best dose, toxicity is seen with each of these agents. Preventing and managing chemotherapy toxicity are crucial to optimizing patient outcomes (e.g., curing, prolonging life, or palliating symptoms). The decision to start chemotherapy depends greatly on the overall patient picture, with emphasis on PS and comorbid conditions. Knowledge of the major adverse effects of individual regimens is important for anticipation...

Complications of chemotherapy

Before the era of effective chemotherapy, disseminated testicular cancer was uniformly fatal 51 . Fortunately, new therapeutics emerged that have changed the face of testicular cancer 52,53 . The current regimen for chemotherapeutic intervention provides exceptional survival, greater than 80 , even in highly advanced stages of tes-ticular neoplasms 54 . The standard of treatment for patients with disseminated germ-cell tumors is currently a regimen of bleomycin, an antibiotic with antineoplastic activity, etoposide, a DNA topoisomerase inhibitor, and cisplatin, an alkylating agent. This multidrug chemotherapeutic regimen is commonly referred to as BEP. Patients with resistant disease or those who experience relapse will undergo salvage chemotherapy with cisplatin, ifosfamide, and either vinblastine or etoposide. This salvage regimen provides a durable result in approximately 20 to 25 of these previously refractory patients 55 . Even among patients unresponsive to salvage chemotherapy,...

Breast Cancer in the Twentyfirst Century

Breast cancer fits into a twenty-first century phenomenon. . . . The critical shared issue of our time is moving from an age of extinctions to an age of renewal and sustainability. One of the principal hopes for this is the environmental health movement. . . . the role of the breast cancer movement as a vanguard of the environmental health movement is not just of parochial interest to breast cancer patients it is core to the future of life on earth. MICHAEL lerner, Breast Cancer and the Environment Breast cancer, as Michael Lerner declared at the International Summit on Breast Cancer and the Environment in 2002, is a twenty-first-century phenomenon. By this the founder of Commonweal (the highly respected cancer and environmental health center in Bolinas, California) meant not that breast cancer is a disease new to the twenty-first century but, rather, that breast cancer engages twenty-first-century issues of environmental health that are crucial to the future of life on earth. In...

The Use of Chemotherapy and Chemoradiation

Penis Needle

Combination therapy in the form of chemotherapy and radiotherapy is utilized in an attempt to improve the long-term outcomes for patients diagnosed with urethral Chemotherapy male urethra and were treated with chemotherapy consisting of 5-FU and Mitomycin C with concurrent external beam radiotherapy to the genitalia, perineum, and inguinal and external iliac lymph nodes.6 The treatment schedule is summarized below (Fig. 8.8).

The Role of Chemotherapy in Larynx Organ Preservation

Laryngeal Cancer Treatment

The trials evaluating induction chemotherapy, while disappointing with regard to improving survival as an endpoint, did provide the backdrop for current organ preservation strategies. Investigators observed that some patients refused surgery after initial chemotherapy and proceeded with radiation alone.87 Some of these patients were controlled over the long term without surgery, and there appeared to be a positive correlation between initial response at the primary site to induction chemotherapy and the likelihood of disease control with radiation alone. Pilot organ preservation studies demonstrated that induction chemotherapy followed by definitive dose radiation, with surgery to the primary site reserved for non-response or relapse, was a feasible approach.88,89 Reported survival results in selected patients were comparable to those anticipated with standard surgery and radiotherapy, but surgery to the primary site was avoided in a significant proportion of patients (Figure 22-1)....

Morbidity of retroperitoneal lymph node dissection after chemotherapy

RPLND after induction chemotherapy is a challenging operation because of the complexity of the procedure and the severe desmoplastic reaction from prior exposure to chemotherapeutic agents. The morbidity of post-chemotherapy RPLND ranges from 18 to 29 in the standard group 23,79,80 and up to 39 in the complicated RPLND group 81,82 . Perioperative complications may be subdivided into pulmonary, infectious, lymphatic, vascular, neurologic, and gastrointestinal complications.

Sequential Chemotherapy

The sequential integration of chemotherapy with locoregional treatment can be done in three main ways as induction or neoadjuvant chemotherapy prior to surgery and or radiation, as an adjuvant after locoregional treatment, or as a combination of these approaches. Given the impressive response rates Chemotherapy induction chemotherapy followed by radiation therapy or previous chemotherapy or radiation therapy paclitaxel 3-hour previous chemotherapy Patients with advanced head and neck tumors chemotherapy the induction chemotherapy tumors chemotherapy followed by surgery or radiotherapy observed in untreated patients with the cisplatin-based combination chemotherapy discussed previously, there initially was great enthusiasm from phase II studies that sequential strategies would improve survival in these patients.48 As summarized below, randomized trials failed to demonstrate a significant survival benefit, although in selected studies the pattern of failure was altered compatible with a...

Etoposide and cisplatin adjuvant chemotherapy

In patients who have high-volume metastases, the use of well-tolerated adjuvant chemotherapy should be strongly considered. Substitution of etoposide for vinblastine in two randomized Based on the efficacy and tolerability of four cycles of EP in patients who had disseminated GCT, a prospective trial of two cycles of EP was conducted in the adjuvant setting 31 . Eligibility for the study was restricted to patients who had pN2 disease at RPLND, representing a group of patients who have an otherwise 50 or greater probability of relapse in surveillance. Fifty evaluable patients were treated in the study (Table 3) 31 . None of the 50 patients had relapsed at a median follow-up of 35 months (range 12-72 months) 31 . The stomatitis, dermatologic toxicity, and ileus reported with vinblastine-based adjuvant chemotherapy were not present in the etoposide-based chemotherapy 5,20,26,32 . No Past efforts to reduce chemotherapy-related toxicity in the management of advanced GCT also included...

Cancer Chemotherapy and Treatment

Each category of chemotherapy drugs has some similar side effects, usually on the most rapidly-growing cells of the body. However, there are unique toxicities of various pharmacologic categories of antineoplastic agents. Anthracyclines cause cardiac toxicity, which is related to the cumulative dose. Tubulin-interactive agents are associated with neuropathy and ileus. Alkylating agents are associated with secondary malignancies. Because of the severe toxicities associated with many of the chemotherapy agents, safety precautions must be in place to prevent chemotherapy errors, accidental chemotherapy exposures, and overdosages. Clinicians should play a role in chemotherapy safety, patient education, and monitoring patient response to therapy. For example, cumulative doses of anthracyc-lines should be monitored along with signs and symptoms of heart failure. Clinicians also should monitor for drug interactions between other current medications and chemotherapy agents. Cancer treatments...

The Risk of Chemotherapy Resistance

When Flavia and Walter agreed to the two-year course of chemotherapy for Mario, they were relying on the hope that Mario's MLL leukemic cells would not become resistant to the potent combinations of drugs that would be visited on him by Scott Armstrong, Lew Silverman, and their colleagues. Mario's parents did not want to contemplate that risk closely they asked few questions about the development of resistance. But the risk never left Scott's mind as he began the complex protocol he would deliver over the next twenty-four months. Scott and Lew had only a student's view of cancer chemotherapy resistance. They had never studied the phenomenon in the laboratory and probably were unaware of how mysterious the resistance was to those who had encountered it during the early days of chemotherapy for leukemia in the 1960s. I had seen chemotherapy resistance develop rapidly in the children I cared for at NCI in the 1950s. At that time, I had no idea how it happened. Somehow cells that appeared...

Selective Intraarterial Chemotherapy

The selective administration of chemotherapy through intra-arterial infusion offers the advantage of a more direct drug delivery to the tumor site at a higher local concentration than can be achieved with systemic therapy. This technique was initially attempted with modest results similar to those obtained by surgery and postoperative radiation ther-apy.53 Shibuya suggested that one problem was the multiplicity of feeding arteries supplying the maxillary sinus causing an irregular, lower distribution of intra-arterially infused chemotherapy.54 A study by Lee reviewed 24 patients treated with selective intraarterial cisplatin and bleomycin through the internal maxillary artery, combined with intravenous 5-fluo-rouracil, and followed by radiation therapy and or surgery. Although long-term follow-up was not available, 43 percent achieved a complete response, 48 percent a partial response, and only 9 percent a minimal response.37 Two patients died from complications related to the...

Concomitant Chemotherapy

The concomitant integration of chemotherapy and radiation therapy for the treatment of advanced disease has been one of the areas of greatest interest in head and neck oncology during the last decade. Potential radiation enhancement, the simultaneous treatment of both locoregional and distant disease in a dose-intense manner, and shorter treatment times make the approach particularly appealing. Interestingly, the approach is much older than the relatively recent surge in interest would suggest. Randomized studies suggesting a benefit with the concomitant integration of chemotherapy with radiation therapy date back over 2 decades.1-6,63-68 Interest in strategies incorporating sequential chemotherapy was of greater interest during the 1980s, at the expense of the development of concomitant ones. Given the prospect for improved local control, unresectable disease has been the focus more often than not in studies to date. Encouraging results as summarized below, however, are prompting...

Historical Perspective On Clinical Trials In Breast Cancer

Scientific understanding of the biology of breast cancer has changed radically in the past 50 years. Results of large randomised trials have played a major role in this transition. From the nineteenth century and up into the 1970s, breast cancer was understood to be a local regional disease that spread by direct extension along lymphatic pathways to distant sites. This concept gave rise to the surgical methods promoted by W.S. Halsted14-16 around the turn of the twentieth century, i.e., extensive resection of the breast, regional lymphatics, lymph nodes and muscle. This surgical technique, known as radical mastectomy, remained the principal approach to treatment of breast cancer throughout the first half of the century, sometimes combined with radiotherapy. When the concept of large-scale randomised clinical trials to investigate alternative therapies was proposed in the 1960s, controversy arose among breast cancer researchers as well as in other medical fields. In a heated exchange,...

Intra Arterial Chemotherapy

Intra-arterial chemotherapy is the process by which chemother-apeutic agents are delivered directly into the arterial tumor supply (usually in gliomas) via a microcatheter. Most gliomas are treated by a combination of surgery, radiation therapy, and standard intravenous chemotherapy. However, selective intra-arterial chemotherapy was rendered possible by introduction of the microcatheter and has been undertaken in limited fashion in an effort to expose the tumor to the largest concentration of chemotherapeutic agent while limiting systemic effects. After determining the vascular territory encompassing the glioma, a microcatheter is navigated into the intracranical circulation to an optimal location depending on predicted tumor supply. Microcatheter positions beyond the ophthalmic artery origin were associated with diminished risk of visual impairment.2 Infused chemotherapeutic agents have included carboplatin,11 5-fluorouracil, cisplatin, nitrosourea compounds,9 and other agents that...

Chemotherapy Principles

Chemotherapy can be defined as administering pharmacologic agents that either destroy tumor cells directly or modify their biology such that tumor growth is impaired. Chemotherapy plays an important role in treating tumors affecting the nervous system. This role is expanding, and many options are now available to treat a wide variety of tumors. For example, whereas chemotherapy has been widely accepted in the management of highly malignant tumors such as glioblastoma multiforme, its use is now being considered in such nontraditional scenarios as lower grade astrocytomas and recurrent meningiomas. In addition, more cytostatic agents are being used that take advantage of insights into tumor biology. The way chemotherapeutic agents are administered is also being revised, with increasing emphasis on local delivery. In this chapter we review general chemotherapy principles with particular emphasis on how they may apply to nervous system tumors.

Neoadjuvant Chemotherapy

Interestingly, durable complete remissions can be obtained in patients with primary resectable and nonresectable locally advanced nodal and soft tissue disease by neoadjuvant chemotherapy followed by surgical removal of residual disease.9 10 In a review on advanced penile carcinoma, Culkin and Beer combined the results of all available studies on cisplatin-based induction chemotherapy. 1 1 Clinical responses were found in 24 of 35 patients (69 ) and 15 of the responding patients (43 ) underwent subsequent surgery. Eight patients (23 ) were alive without evidence of disease after 1-10 years of follow-up. In our own institution over a 33-year period, a total of 20 patients were treated with induction chemotherapy in an attempt to downstage primary unresectable inguinal lymphadenopathy. Five different chemotherapy regimens were used. An objective tumor response was achieved in 12 of 19 evaluable patients. The overall 5 year survival was 32 , while there was a significant difference (p...

Chemotherapy for Thyroid Cancer

COMBINATION CHEMOTHERAPY IN SALIVARY GLAND CANCER BLM bleomycin CDDP cisplatin CT chemotherapy CTX cyclophosphamide DOXO doxorubicin 5-FU 5-fluorouracil EPI behaviors that should be considered when making decisions regarding the role of systemic therapy. Chemotherapy is most commonly considered after surgery and or radiation therapy (external beam, and if applicable, radioactive iodine RAI ) have failed, as induction adjuvant chemotherapy is of unproven benefit. Chemotherapy by itself is not a curative modality. The available data to aid clinical decision-making is limited in both quantity and quality. Investigational studies from the start are appropriate to consider. For differentiated histologies (eg, papillary or follicular), radioactive iodine (RAI) is the initial systemic therapy of choice. Before considering chemotherapy, evaluating the adequacy and quality of prior therapy with RAI should be the first step. For example, recent intravenous iodinated contrast, con...

Adjuvant Chemotherapy

The role of adjuvant chemotherapy is uncertain. Studies published in the 1980s suggested a potential benefit of adjuvant chemotherapy in patients with documented inguinal metastases who were treated with inguinal lymphadenectomy combined with adjuvant chemotherapy using VBM (vincristine, bleomycin, methotrexate).9,18 However, these small uncontrolled studies do not justify the implementation of adjuvant chemotherapy as standard care.

Combining Antiangiogenic Agents with Metronomic Chemotherapy Enhances Efficacy against Latestage Pancreatic Islet

Recently, a new twist on chemotherapeutic trial design has been developed by two groups (Browder et al. 2000 Klement et al. 2000 Kerbel et al. 2002), who discovered that chemotherapeutics, when given in much different dosing schedules, can act as antiangiogenic agents, even in tumors that are resistant to the particular drug. Both the Folkman and Kerbel laboratories showed that by altering the dosing regimen to one of regular inoculations without rest periods at lower (1 3-1 10 of MTD) concentrations, so-called 'metronomic' or antiangiogenic chemotherapy dosing, traditional cytotoxic drugs could produce antian-giogenic effects in xenotransplant models, even against drug-resistant tumors (Browder et al. 2000 Hanahan et al. 2000 Klement et al. 2000). How is such an effect possible What had been historically ignored with chemotherapeutic strategies was the possibility that proliferating tumor endothelial cells could be killed by cytotoxic drugs. Cytotoxic killing was not evident because...

Chemotherapy

Management options for adults with low-grade astrocytomas (LGAs) include observation, surgery, radiation, or chemotherapy, but there is no well-established standard approach. Patients who have undergone a complete radiographic resection of their tumor are often followed with surveillance MRI scans and treated at progression. In the past, patients who have undergone subtotal resections have been treated with radiation therapy. However, there is now a trend to avoid up-front radiation based on an EORTC study that suggests there is no survival benefit.34 Adjuvant chemotherapy after radiation has not typically been given. However, the RTOG is conducting a study that addresses the question of a possible benefit with this approach. In this trial patients older than 40 or those with incompletely resected low-grade tumors will receive radiation with or without PCV. The role of chemotherapy in adult patients with LGA has not been extensively investigated. This section will focus on the use of...

Chemotherapy safety

One of the first Institute of Medicine reports starts out with a patient who died from an overdose of chemotherapy the patient did not have an immediately life-threatening cancer, so her death was hastened by a medication error. Chemotherapy agents may cause harm to patients, health care workers, and the environment if not handled correctly. Because of the severe toxicities associated with many of the chemotherapy agents, safety precautions must be in place to prevent chemotherapy errors, accidental chemotherapy exposures, and overdosages. The Oncology Nursing Society and the American Society of Health-System Pharmacists have information to assist in the safe handling of chemotherapy agents.49 National, state, and local regulations regarding the safe disposal of chemotherapy agents and the equipment used to administer them need to be followed to protect the environment. Table 88-8 Dosing Adjustment Guidelines for Chemotherapy for Renal Dysfunction Each organization should have...

Primary chemotherapy

In distinction to adjuvant chemotherapy given to men who have PS II disease after RPLND, primary chemotherapy refers to treatment administered to men who have CS I NSGCT after orchiectomy. The goal of primary chemotherapy is to minimize the risk for relapse and to allow men to avoid RPLND and the longer course of chemotherapy administered for patients who relapse on surveillance. The rationale underlying this approach derives from the 30 relapse rate seen during surveillance and the 20 to 25 risk for needing systemic chemotherapy after RPLND given either as adjuvant therapy for PS II disease or as treatment of relapse 8,9,12,41 . Primary chemotherapy offers patients the greatest chance of being relapse-free with any single treatment modality. Only limited long-term follow-up data are available, however, and there are lingering concerns about the potential risk for late chemotherapy-refractory relapses and late chemotherapy toxicity. Primary chemotherapy has been investigated in at...

Cancer Prevention And Environmental Risk

In a speech that she gave at a community forum in 1996 entitled The Politics of Breast Cancer, Nancy Evans, then president of BCA, quoted this passage, which she attributed to a speech delivered by Sandra Steingraber in Santa Fe, New Mexico, in 1994. I quote it here partly to illustrate the way discourses traveled within the culture of environmental cancer activism. 3. Quotation taken from AstraZeneca International, Community and Company Projects US Breast Cancer Awareness Month, http www.astrazeneca.com communityproject ii0.aspx. 4. Although NBCAM's genealogy can be traced to 1985, there was no National Breast Cancer Awareness Month that year. Rather, there was a week of activities designed around the promotion of breast cancer early detection. As part of this effort Imperial Chemical Industries created a public service announcement featuring Susan Ford Bales and her mother, Betty Ford. The public service message elicited such a positive response that it led to the program's...

Patient Empowerment and Feminist Treatment Activism

If each woman with breast cancer understood medicine's limited ability to control the disease, our reliance on physicians, tests, and medical interventions would be enormously reduced. The power of these institutions over us would dwindle accordingly. Without the Rosy Filter, women with breast cancer would gain the right to map our own future, within the very real constraints imposed by a life-threatening disease. In 1985 Jackie Winnow was diagnosed with breast cancer while serving as the coordinator of the Lesbian Gay and AIDS Discrimination Unit of the San Francisco Human Rights Commission. Despite her knowledge, position, and experience, Winnow was shocked to discover that even in the Bay Area, the epicenter of health consciousness and health activism, there were very few resources available for women with cancer and no collective consciousness of the political dimensions of the disease. Shortly after her diagnosis, Winnow began attending a women's cancer support group led by Carla...

The Regime Of Medicalization

Daniel De Moulin, A Short History of Breast Cancer (Boston Martinus Nijhoff, 1983), 2. 14. Quoted in Robert Aronowitz, Do Not Delay Breast Cancer and Time, 1900 1970, The Milbank Quarterly 79 (2001) 365. 50. Barron H. Lerner, Inventing a Curable Disease Historical Perspectives on Breast Cancer, in Breast Cancer Society Shapes an Epidemic, ed. Anne S. Kasper and Susan J. Ferguson, 25-50 (New York St. Martin's Press, 2000), 30. 51. Joan Austoker, The 'Treatment of Choice' Breast Cancer Surgery, 1860-1985, Society for the History of Medicine Bulletin 38 (1985) 100-107 Lerner, Inventing a Curable Disease. Also see Barron H. Lerner, Great Expectations Historical Perspectives on Genetic Breast Cancer Testing, American Journal of Public Health 89 (1999) 939. 52. Lerner, Inventing a Curable Disease. Technically, breast cancer was actually reinvented as a curable disease, since it had already been invented as a curable disease by quacks and sellers of patent medicines. 54. Halsted first...

Biomedicalization And The Biopolitics Of Screening

Who are asymptomatic, appear to be cancer-free, and have never been diagnosed or treated for breast cancer. This has the unfortunate consequence of implying that women who are symptomatic, who show evidence of cancer, or who have been diagnosed or treated for breast cancer are unhealthy, and vice versa, that women who appear to be cancer-free and have never been diagnosed with cancer are necessarily healthy. Neither of these implications is true, obviously, and neither is intended. Healthy, in the context of my usage, is an adjective used for a woman who has no known history of breast cancer. 3. For additional explorations of the social, cultural, and political dimensions of the discourses and practices of breast cancer risk and screening, see Deborah Lupton, Femininity, Responsibility, and the Technological Imperative Discourses on Breast Cancer in the Australian Press, International Journal of Health Services 24 (1994) 73 89 Cartwright, Screening the Body Patricia A. Kaufert, Women...

Biomedicalization and the Anatomo Politics of Treatment

Why did the identity of being a woman with breast cancer change from passivity to action . . . What impelled women with breast cancer to break out of their isolation and assemble under the banner of a new social movement patricia a. kaufert, Women, Resistance, and the Breast Cancer Movement The biopolitics of screening, as we saw in chapter 3, changed the popular discourses and public administration of breast cancer. As it did so, it reconstituted ordinary women as risky subjects and repositioned them along the breast cancer continuum. This chapter explores the other half of the transformation in disease regimes the anatomo-politics of treatment, focusing on key changes in the diagnosis, decision making, treatment, and rehabilitation of breast cancer patients. This chapter is not a history of cancer policy, cancer research, or cancer medicine but, rather, a genealogy of the breast cancer patient within the regime of biomedicalization. My analysis focuses on the medical practices and...

Iciety Fdr Control Of Cancer

Breast cancer treated early, according to this poster, led to a 70 percent cure rate, whereas breast cancer treated late resulted in a cure rate of only 10 percent. Other posters proclaimed don't fear cancer fight it and Don't Fight Cancer Alone. Another series of posters promoted surgery, radium, and x-rays as the treatments offered by reputable physicians and cautioned that other methods of treatment are experimental or quackery. The reorganized ACS continued its campaign of medicalization through the development of early detection campaigns that supported the interests of private physicians by channeling more women into the diagnostic and treatment pipeline. A new campaign was launched in the 1950s called Every Doctor's Office a Cancer Detection Center. This slogan perfectly captures the ACS's dual focus on transforming symptomatic women into cancer patients and integrating ordinary doctors into the larger regime of practices. This campaign was designed with detection...

Social Movements Without The Sovereign

Unless otherwise noted, the source for all facts and figures in this chapter's discussion is Breast Cancer Facts and Figures, 2005 2006. 8. For a recent overview of disparities in breast cancer, see Judy Ann Bigby and Michelle D. Holmes, Disparities across the Breast Cancer Continuum, Cancer Causes and Control 16 (2005) 34 44. See also American Cancer Society, Breast Cancer Facts and Figures, 2005-2006. 9. Early Stage Breast Cancer Rates Are Rising, Medical News Today, April 12, 2005. 10. Barron H. Lerner, Fighting the War on Breast Cancer Debates over Early Detection, 1945 to the Present, Annals of Internal Medicine 129 (1998) 74-78. 12. American Cancer Society, Breast Cancer Facts and Figures, 2005 2006, 3. 13. The first study to demonstrate a decrease in breast cancer incidence rates in the United States was published in 2007. The study showed that incidence rates declined by a dramatic 6.7 percent in 2003 the first significant decline in breast cancer incidence recorded by cancer...

Early Detection And Screening Activism

Lisa Belkin, How Breast Cancer Became This Year's Hottest Charity, New York Times Magazine, December 22, 1996, 40 57, quotation on 45. 2. For a thorough and thoughtful examination of corporate cause-related marketing and the breast cancer movement, see Samantha King, Pink Ribbons, Inc. Breast Cancer Culture and the Politics of Philanthropy (Minneapolis University of Minnesota Press, 2006). 4. Susan Braun, The History of Breast Cancer Advocacy, Breast Journal 9 (2003) S103. For an analysis of the culture of volunteerism in a local chapter of the Komen Foundation, which included a rejection of an activist identity, see Amy Blackstone, 'It's Just about Being Fair' Activism and the Politics of Volunteering in the Breast Cancer Movement, Gender and Society 18 (2004) 350 68. 5. Suein L. Hwang, Linking Products to Breast Cancer Fight Helps Firms Bond with Their Customers, Wall Street Journal, September 21, 1993. 7. Samantha King, An All-Consuming Cause Breast Cancer, Corporate Philanthropy,...

Roni Peskin Mentzer

I also extend a very special thank you to the following women, each of whom played an integral role in the development of the women's cancer community and generously contributed time, energy, and intellect to teach me about the biopolitics of breast cancer Merijane Block, Judy Brady, Barbara Brenner, the late Susan Claymon, Carla Dalton, Diane Estrin, Wendy Favila, the late Francine Levien, the late Shannon McGowan, Roni Peskin-Mentzer, and Wanna Wright. Second, and closely related, I express my deepest gratitude and appreciation to the dozens of women living with breast cancer who allowed me to interview them in confidence, usually in the privacy of their homes, and whose names do not appear in this book. The stories they shared and the forms of engagement, exchange, and expression that I witnessed in the support groups they attended taught me to pay attention to the deeply gendered and embodied dimensions of this disease. I am eternally grateful for their openness and generosity of...

Acronyms

BCA Breast Cancer Action BCDA Breast Cancer Detection Awareness project BCDDP Breast Cancer Detection Demonstration Project BCEDP Breast Cancer Early Detection Program BCERC Breast Cancer and the Environment Research Centers BCF Breast Cancer Fund BCPT Breast Cancer Prevention Trial BCRP California Breast Cancer Research Program IBIS-I International Breast Cancer Intervention Study I MBCW Marin Breast Cancer Watch NABCO National Association of Breast Cancer Organizations NBCAM National Breast Cancer Awareness Month NBCC National Breast Cancer Coalition

The effect on human health

At the Royal College of Nursing Conference (Frith 2004) showed that women recovering from breast cancer were significantly better at managing their disease if they owned a pet and felt less disfigured following surgery. The psychological benefits of animals to humans are that they are aesthetically pleasing, they instigate a nurturing instinct in man and respond readily to human affection, all of which help to reduce stress and promote feelings of self-worth.

Case finding and testicular selfexamination

Having concluded that TSE may be beneficial at least for men who have risk factors for testicular cancer, if not for all young men, its teaching should emphasize the following points. First, men must gain familiarity with the surface, texture, and consistency of their testicles in the normal state. Second, the ideal time for TSE is during or after a warm bath or shower. Third, the man examining himself should rotate both testicles between thumb and forefinger until he determines that the entire surface of each is free of lumps. Fourth, the man should learn the location of the epididymis and that this structure is not a tumor. Fifth, any detected lump should be reported to a physician immediately 65 . Most importantly, as noted earlier, physicians must convey the benefit of TSE to affect the intention to perform it regularly. Education must include possible consequences of not performing TSE, such as delay in diagnosis with resulting advanced stage of disease the need for intensive...

Clinical Trials And Treatment Response

Many nervous system tumors present specific challenges to this chemotherapy evaluation schema. Antitumor response in clinical trials is usually measured by decreased tumor size shown on magnetic resonance imaging (MRI). Unfortunately, with diffuse central nervous system (CNS) tumors such as glioblastoma, exact tumor size is often difficult to determine on MRI. This can be particularly true when patients have previously undergone resection, irradiation, or chemotherapy. Furthermore, cytostatic chemotherapies may not have similar dose-limiting toxicities to standard cytotoxic agents. This can make it difficult to determine maximum tolerated dose in phase I trials. Despite these limitations, the traditional phase I through tive chemotherapies for nervous system tumors. Surrogate biologic or pharmacologic end points have been developed in many cases to prevent these difficulties.

Multimodality Treatment Intent And Timing

Patients with nervous system tumors usually receive chemotherapy as part of a multimodality treatment approach also involving surgery and radiation therapy. Chemotherapeutic agents may be given alone or in combination. Combining agents with different mechanisms of action and different toxicities is attractive and has been effective in many tumor types. Unfortunately, few chemotherapy combinations have proved more effective than single agents for nervous system tumors. Chemotherapy can be administered with curative intent, to prevent disease recurrence, or as a palliative measure. Chemotherapeutic agents may be given at different times relative to diagnosis and other treatments. Adjuvant chemotherapy is delivered after diagnosis and initial therapy (e.g., surgery and irradiation for a glioblastoma) but before recurrence. In other words, adjuvant therapy is given in the setting of nonprogressive disease. Sometimes chemotherapy is administered concurrently with other initial therapies...

Strategies To Increase Systemic Chemotherapeutic Efficacy

Other strategies include administering high-dose chemotherapy and inhibiting drug resistance. High-dose chemotherapy has been proposed in the hope that higher serum drug levels will result in greater delivery across the BBB. This is typically accompanied by autologous bone marrow or stem cell transplant as a rescue from the marked myelosup-pressive effects of high-dose cytotoxic chemotherapy. Although this strategy has shown some promise in children with medul-loblastomas and germ cell tumors, the results have been much less favorable for adults with malignant gliomas. Several strategies have been proposed for inhibiting drug resistance. For example, the DNA repair enzyme O6-AGAT can be inhibited using the agent O6-benzyl guanine (O6-BG). This is currently in clinical trials in combination with a number of alkylating agents. In addition to efforts to improve upon systemic chemotherapy, other strategies have been employed for local chemotherapeutic...

Cytotoxic Chemotherapeutic Agents

Cytotoxic chemotherapeutic agents can be defined as those that inhibit tumor growth by killing tumor cells directly. These agents rely on tumor cells' dividing more rapidly than normal cells to achieve an acceptable therapeutic index. Still, their actions are necessarily nonspecific and many common cyto-toxic chemotherapy side effects (e.g., myelosuppression, alopecia) reflect effects on normal dividing cells. General indications for cytotoxic chemotherapy include curing certain tumors, palliating symptoms, or prolonging progression-free survival. Most patients with a CNS tumor receive chemotherapy for this last reason. Relative contraindications include active infections, limited probability of prolonged survival even if tumor regression occurs, and severe debilitation.

Temozolomide Procarbazine and Dacarbazine

Procarbazine and DITC are methylating agents that produce single-strand DNA breaks. Procarbazine has good oral bioavailability. Its active metabolite acts as a cell cycle-nonspecific agent that inhibits DNA, RNA, and protein synthesis. Major toxicities include fatigue, nausea and vomiting, myelosuppression, and rash. It also acts as a monoamine oxidase inhibitor therefore patients taking procarbazine need to avoid tyramine-containing foods such as red wine, sharp cheddar cheese, and flava beans. Procarbazine can be given as a single agent but is more commonly administered in combination with CCNU and vincristine (PCV chemotherapy). It has activity against malignant gliomas, low-grade gliomas, primitive neuroectodermal tumors (PNETs), and primary CNS lymphoma.9,11

Vinca Alkaloids and Epipodophyllotoxins

Vincristine and vinblastine are vinca alkaloids that act on tubulin to inhibit microtubule assembly. They result in S-phase-specific mitotic arrest. Resistance is mediated by the p170 membrane glycoprotein. These agents are water soluble, must be given intravenously, and have poor BBB penetration.8 Toxicities are primarily neurologic, including peripheral neuropathy and (as a result) constipation. Vinblastine is seldom administered to patients with nervous system tumors. Vin-cristine is commonly used in combination with procarbazine and CCNU (PCV chemotherapy) and may have activity against malignant gliomas, PNETs, low-grade gliomas, ependymomas, and primary CNS lymphomas.

Intervention Versus Observation

Patients with a family history of thyroid cancer are much more likely to develop thyroid cancer. Familial medullary thyroid cancer, with or without multiple endocrine neoplasia, should always be excluded. Familial non-medullary thyroid cancer, with or without Cowden's syndrome (multiple hamartomas, breast cancer, colon cancer, and nodular goiter), Gardner's syndrome, familial polyposis coli, or Carney's syndrome (schwannomas, myxomas, adrenal tumors, pigmented skin lesions), should also be considered.

Strategies to Relieve Pain

Whenever possible, the first and best way to relieve cancer pain is to eliminate or modify the source of the pain by removing or shrinking the cancer that is causing the pain, with surgery, radiation, or chemotherapy (including hormones). However, these approaches are sometimes impractical and even unsafe. First, each of these kinds of treatments has some risk. Second, many patients are not candidates for surgery, especially if the cancer has spread or if a patient's overall condition is poor. Finally, not all tumors respond well to radiation and chemotherapy. Even when they do, treatments sometimes have to be limited because they can cause reduced blood counts and may make patients feel run-down. Also, most of these treatments produce pain relief only slowly, and some may actually worsen pain or, as a side effect, cause new pain. Nevertheless, these strategies are often very effective in relieving pain, even when a complete cancer cure is unlikely. Since these antitumor strategies to...

Mghr on for 1214 hours off for 101 hours

IHD or cardiovascular events with HRT in postmenopausal women. ' In fact, HRT appeared to be harmful in this patient population, increasing the risk of thromboem-bolic events and breast cancer. Current guidelines recommend against the use of HRT to reduce cardiovascular risk.1 Furthermore, the clinician should consider discontinuing HRT therapy in women who suffer an acute coronary event while receiving such therapy.

Key Concepts in Evidence Based Prevention

To determine whether a screening test is a good assessment, test accuracy (i.e., sensitivity and specificity) and the prevalence of the disease in the population to be screened must be considered. Screening for colorectal cancer, breast cancer, and cervical cancer has proven to be effective in decreasing the morbidity and mortality rates of these cancers.

The Darwinian paradigm in oncology

So, the most advanced oncological research has reached the agreement that cancers are conventional Darwinian processes of repeated cycles of mutations and selections, and that Darwinian models of cancer progression can explain most tumor phenomenology. Environment contributes to cancer development with mutagenic chemicals and conditions that increase cell replications, thus creating the opportunity for mutations to occur and for the somatic selection of the advantageous ones to take place. Mutations that allow cancer cells to produce their own signals to stimulate mitosis, to suppress contact inhibition, to evade apoptosis, to attract the vascular system and to spread or metastasize can have a selective advantage. Somatic mutation and selection are very important for cancer treatment since that, as tumors, can evolve resistance to chemotherapy (Michor, Nowak, and Iwasa 2006).

Burden of Disease

Breast cancer is the second leading cause of cancer deaths in U.S. women in 2008, an estimated 182,460 cases of invasive cancer and 67,770 cases of in situ breast cancer were diagnosed, with 40,480 breast cancer deaths (ACS, 2009). The risk for breast cancer increases with age the 10-year risk for breast cancer is 1 in 69 for a woman at age 40 years, 1 in 42 at age 50, and 1 in 29 at age 60 (SEER, 2009). Several tools are available to predict risk of developing breast cancer for individual women (e.g., BRCAPRO, Gail, Claus, Tyrer-Cuzick). All these tools incorporate age and number of first-degree relatives with breast cancer into the calculations (Nelson et al., 2005). One example is found at www.cancer.gov bcrisktool .

Accuracy of Screening Tests

The prevalent methods of breast cancer screening are mam-mography, clinical breast examination (CBE), and self breast examination (SBE), or breast self-examination (BSE). The sensitivity of mammography ranges from 77 to 95 for cancers diagnosed over the following year, and specificity ranges from 94 to 97 . Sensitivity is lower in women younger than age 50 and in women taking hormone replacement because of increased breast tissue density. Specificity increases with shorter screening intervals and availability of prior mammograms. Adequate evidence suggests that teaching BSE does not reduce breast cancer mortality. The evidence for additional effects of CBE independent of mammography on breast cancer mortality is inadequate. The sensitivity of CBE ranges from 40 to 69 and specificity from 86 to 99 (Humphrey et al., 2002).

Effectiveness of Early Detection and Intervention

In this age group, although false-positive results are a concern. BSE has not been shown to reduce breast cancer mortality or significantly alter the stage at diagnosis. CBE has not been evaluated independent of mammography screening with CBE and mammography is comparable to using mam-mography alone (Humphrey et al., 2002 USPSTF, 2009). Potential harms of breast cancer screening stem from false-positive results. Harms include unnecessary follow-up testing and invasive procedures, anxiety, and additional medical expense.

Symptom Clusters That Affect Quality Of Functional Outcomes

Patients with brain tumors experience a number of adverse symptoms that negatively affect their ability to function in usual work, leisure, and social roles. These include cognitive impairment, neurologic signs and symptoms, fatigue, mood disturbance, sleep disturbance, and sexual dysfunction. These symptoms occur in a majority of patients on active therapy, and occasionally are the first symptoms that herald the initial diagnosis. In addition, these symptoms often persist after treatment is discontinued. Most patients who have a brain tumor experience cognitive impairment, including restricted working memory capacity (e.g., how much information the person can process on-line), distractibility, and problems multitasking. They often experience generalized slowing and must exert increased effort when performing even routine activities. In addition, many patients experience fatigue related to their disease and treatment that compounds cognitive impairment. This fatigue is an unusual,...

Treatment Specific Factors

Radiation therapy to the brain is widely known to cause injury to white matter and cognitive impairments related to frontal-subcortical dysfunction. It also causes significant fatigue in fact, cancer patients receiving radiation therapy to non-CNS sites (e.g., prostate or breast cancer) also experience fatigue during treatment that is centrally mediated. Induction of inflammatory cytokines, disruption of the hypothalamic-pituitary-adrenal axis, and alterations of neurotransmitters have been implicated in radiation-induced fatigue and cognitive impairment. Chemotherapy can also cause additional functional impairments patients often refer to their experience as chemo-brain. The effects appear to vary somewhat depending on the agent administered, but little is known about the actual side-effect profile of most agents other than through self-report and quality of life questionnaires, neither of which capture all significant symptoms. Although most cognitive effects tend to be diffuse and...

B dosefinding trials

With the continuous i.v. administration for 21 days every 28 days, the MTD was 0.53 mg m2 day (220). The steady-state concentration of lactone topotecan was only approximately 4 ng ml. No consistent relationship between drug level and hematological toxicity was found. Of interest, the Phase I study showed several partial tumor responses in tumor types which were initially chemotherapy resistant (220). In a Phase II study with this regimen in patients with progressive and platinum-refractory ovarian cancer, the response rate was 37 (221).

The Patient with Cancer

Fears of mutilation are common among patients with cancer. The fear of being perceived as lacking ''wholeness'' contributes to depression and anxiety. The young woman with breast cancer who requires a mastectomy fears that she will be rejected as no longer being a complete woman. Supportive family members are the key in reassuring this patient that they will love her just as they have before her surgery. A diagnosis of cancer makes a patient aware of mortality and leads to intense fear of unremitting pain.

Pharmacologic Interventions

Pharmacologic interventions may be extremely helpful in improving a patient's function and general well-being. Clinicians often use psychostimulants to treat the declines in cognitive and emotional functioning that are so ubiquitous among brain tumor patients. Psychostimulants are effective, in part, because they counter the effects that tumor and treatment produce on the monoamine pathways of the frontal-brainstem reticular system. Methylphenidate, dextroamphetamine, and pemoline have each been reported to ameliorate depression and fatigue in cancer patients. In the brain tumor population, only methylphenidate, in immediate release form, has been investigated as a possible treatment for declines in neurocognitive functioning (i.e., neurobehavioral slowing and impairments in attention and working memory). For example, in children with acute lymphoblastic leukemia and malignant brain tumors, treatment with methylphenidate was shown to improve sustained attention.17 In adult patients...

Coactivators and corepressors

Activation of transcription by AR is regulated by a number of cellular proteins that interact with the receptor. The best characterized are the p160 SRC (steroid receptor co-activator) family members SRC-1 NCoA-1 (Alen et al. 1999 Bevan et al. 1999), SRC2 GRIP1 (glucocorticoid receptor-interacting protein 1) TIF2 (transcription intermediary factor 2) (Berrevoets et al. 1998 Kotaja et al. 2002a Shang etal. 2002), and SRC3 ACTR (activator ofthe thyroid and retinoic receptor) AIB1 (amplified in breast cancer) pCIP (p300 CBP co-integrator-associated pro-tein) RAC3 (receptor-associated co-activator 3) TRAM 1(thyroid hormone receptor activator molecule 1) (Anzick et al. 1997 Chen et al. 1997 Li et al. 1997 Torchia etal. 1997), CREB-bindingprotein (CBP p300) (Smith etal. 1996 Aarnisalo etal. 1998 Fronsdal etal. 1998), and P CAF (CBP p300 associated factor) (Reutens et al. 2001). AR recruits p160 proteins, CBP p300 and P CAF to the promoter of target genes (Berrevoets etal. 1998 Shang etal....

Structure Based Drug Design

The mapping of the genome leads us to the identification of targets for therapeutic interventions, as for example chemotherapy, not previously suspected and even allows us to dream of the possibility of correcting genetic defects, enhancing our prospects for a longer and more healthy life, and for devising drugs for specific individuals. Presuming that individual variations in therapeutic response may have a genetic origin, and thus dividing populations into subgroups with similar genetic characteristics, might allow us to prescribe drugs and even dosages within these groups. This form of individual gene typing is already possible, but would be very resource demanding as per days techniques. It is likely that perplexing species differences in response to, for example, chemotherapy, that complicates drug development, may also be understood, when the genome mapping becomes more elaborate.

Conditions that Affect the Maintenance Dose of T4

Several conditions require increasing the dose of T4. Pregnancy is the most important because more T4 is needed during pregnancy in patients with hypothyroidism based on serial serum TSH measurements.77 Similarly, patients with hypothyroidism who take estrogen require more thyroid hormone due to increased thyroid-binding protein by estrogen and subsequent decrease in available FT4.78 Medications to decrease T4 absorption include cholestyramine, sucralfate, ferrous sulfate, aluminum hydroxide, and calcium carbonate.79,80 Increased thyroid hormone replacement should be considered if patients are on these medications. Patients should also take these medications at a different time than when they take their thyroid hormone. Measurement of serum TSH levels is an excellent method to determine the appropriate T4 dose in patients with primary hypothyroidism. In contrast, some conditions require decreased thyroid hormone dose. Androgen therapy decreases T4-binding globulin and increases FT4...

Considerations of Route of Administration

From a clinical point of view, as long as equivalent safety and efficacy can be ensured, the majority of patients prefer oral instead of i.v. administration of chemotherapy, predominantly due to the convenience of administration outside a clinical setting and avoidance of vascular complications, related to i.v. access, including catheter-associated infections or potential thrombosis (249,250).

Squamous Cell Carcinoma Antigen SCC Antigen

Sequentially measured SCC antigen in 16 men with penile cancer. This study once again demonstrated a possible role for SCC antigen in detecting nodal disease and response to treatment. The largest study has been performed by Hungerhuber et al.69 and consisted of 54 patients with penile cancer. SCC antigen levels correlated with tumor burden, increased significantly with extensive lymph node involvement or metastatic disease but did not predict microscopic nodal involvement. Currently, the role of SCC antigen as a prognostic marker is still limited. However, it may be used as an adjunct to sentinel lymph node biopsy in patients placed on surveillance or as a marker for disease response following chemotherapy.

Epidemiology Incidence Prognostic Factors

The median survival for AA ranges between 2.5117 to 3 years.94 Favorable prognostic features94,117 include (1) age younger than 50 years (2) high Karnofsky performance scale (KPS) score (3) a proliferative rate (Ki-67 index) of 5 (4) absence of ring enhancement on CT scan, which reflects the degree of tumor angiogenesis129 and (5) presence of an oligo-dendroglial component.117 Intensive salvage therapy of radiation and chemotherapy adds 1 year of survival.94

Understanding Palliative Therapy

When cancer causes pain, the first thing a doctor will try to do is to eliminate or shrink a tumor as much as possible, using radiation, surgery, or chemotherapy, alone or in combination. Although the patient's comfort is important, it is considered secondary to curing the cancer, especially at the start of treatment, when chances for a cure are best. But even when a cure isn't possible, chemotherapy, radiotherapy, or surgery may be recommended to alleviate pain and other symptoms. Many cancers may be incurable, but few are untreatable. Have previous treatments with radiation, chemotherapy, or surgery made further treatment riskier or less likely to be effective Reducing the pain, discomfort, and odor from tumors that ulcerate the skin, such as certain breast cancers, head and neck cancers, anal cancers, and skin cancers Palliative Chemotherapy Although systemic treatments with chemotherapy and hormone therapy for malignancies are commonly used in attempts to eradicate the cancer,...

Histopathologic Diagnosis Classification and Grading

Gene expression profiling using cDNA microarray technology promises to be as accurate an alternative as histologic diagnosis and a more objective molecular approach than standard histologic criteria, with the prospect of identifying subsets of patients with better prognosis.35 The molecular approach to tumor classification can generate clinically meaningful patient stratification, and more importantly, is an efficient discovery tool for human gliomas, permitting the identification of previously unrecognized, clinically relevant tumor subsets that predict response to chemotherapy or radiation therapy.98 Identification of sets of genes will supplement standard histologic examination in the future as molecular classification of gliomas, using microarrays, elucidates the genetic signature of AAs.59 Two-gene and three-gene combinations thus provide robust classifiers possessing the potential to translate expression microarray results into diagnostic histopathologic assays for clinical use....

What causes prostate cancer What causes prostate cancer to grow

The exact causes of prostate cancer are not known. Prostate cancer may develop because of changes in genes. Alterations in androgen (male hormone) related genes have been associated with an increased risk of cancer. Alterations in genes may be caused by environmental factors, such as diet. The more abnormal the gene, the higher is the likelihood of developing prostate cancer. In rare cases, prostate cancer may be inherited. In such cases, 88 of the individuals will have prostate cancer by the age of 85 years. Males who have a particular gene, the breast cancer mutation (BRCA1), have a threefold higher risk of developing prostate cancer than do other men. Changes in a certain chromosome, p53, in prostate cancer are associated with high-grade aggressive prostate cancer. Oral prednisone Chemotherapy Mitoxantrone Prostate cancer, similar to breast cancer, is hormone sensitive. Prostate cancer growth is stimulated by the male hormones testosterone and dihydrotestosterone (a chemical that...

UpFront Therapy for Anaplastic Astrocytoma

The Northern California Oncology Group (NCOG) stratified a chemotherapy trial based on tumor type. The investigators first compared single-agent BCNU with pCv in patients with malignant glioma. PCV was found to be superior to BCNU but only in the patients with AA.76 This difference was observed in a retrospective analysis of the data. The number of patients with AA was relatively small 37 in the BCNU arm and 36 in the PCV arm. This advantage was not observed for patients with GBM. Retrospective subset analysis of the RTOG brain tumor database failed to show a treatment advantage of PCV over that of carmustine (BCNU).95 A recently published, nonrandomized study of 31 patients with AA focused on predictors of long-term survivorship.103 This study found that significant predictors of survival were preoperative and postoperative KPS score, age under 40, number of chemotherapy cycles, and radiation dose.103 Though virtually every known approved chemotherapy agent has been tested in...

Side Effects and Drug Interactions

In addition, the concomitant use of antiepileptic drugs (AEDs) and chemotherapy may increase clearance of the chemotherapy and therefore decrease response, especially with the taxanes irinotecan65,79and 9-aminocamptothecan.42 Conversely, chemotherapy can cause fluctuations in the serum concentrations of phenytoin, allowing for breakthrough seizure activity and mandating frequent serum monitoring.38,44 Ele vated serum phenytoin levels and clinical toxicity have been reported during treatment with fluorouracil.39 Heightened hema-tologic toxicity has been reported in patients treated with cis-platin-nitrosourea-based chemotherapy and valproic acid.8 Studies are now commonly stratified as to the use of cytochrome p450-inducing AEDs. Patients taking these enzyme-inducing agents (phenytoin, carbamazepine, etc.) are typically entered into companion dose-finding phase I studies of new agents, whereas patients on no AED or non-enzyme inducing AEDs (gabapentin, valproic acid, etc.) are entered...

Biologic Response Modifiers

TMZ is easily tolerated, and attempts have been made to increase response without substantially increasing toxicity. Although TMZ is active against recurrent malignant glioma, responses in many patients are modest and short-lived. TMZ may prove more effective in combination with other agents therefore combination oral chemotherapy for these patients is a particularly attractive approach.62 Investigators paired TMZ with such biologic response modifiers as cis-retinoic acid, a proapoptotic and cellular differentiating agent,55 and interferon-a-2a.127 TMZ has been paired with the matrix-metallopro-teinase inhibitors marimastat45 and Prinomastat with varying results.74 The results of these trials have been compared with TMZ as a single agent (see Table 18-4).

Thyroid Stimulating Hormone Suppression and Miscellaneous Benign Goiters

Given that there is an increased incidence of hypothyroidism and thyroid nodules in children exposed to head and neck irradiation for such conditions as Hodgkin's disease, neuroblastoma, Wilms' tumor, and leukemia, as well as in adults irradiated for breast cancer and lymphoma, the role of TSH suppressive therapy in an expanding population of patients needs to be defined.167168 The question remains whether patients who have been exposed should have suppressive treatment in the absence of nodules as well as the correct management of ultrasonographically demonstrable impalpable nodules. It should also be recognized that the rate of false-negative fine-needle aspiration cytology is significantly higher in the inradiated gland.169 What is also unknown is the role of TSH suppressive treatment during the time of neck irradiation.

Target Driven Drug Discovery 331 Target Identification and Validation

We have used siRNA-mediated down regulation of Cdc7 to determine the function of the kinase in human cells and to understand how normal and tumor cells react to inhibition of Cdc7. We found in a wide panel of cell lines that, consistent with its role in promoting S-phase, Cdc7 depletion causes a marked inhibition of DNA synthesis that correlates with lack of phosphorylation of the Mcm2 sub-unit of the DNA replicative helicase, the Mcm2-7 complex (Fig. 3-1, Panel A). Unlike all current DNA replication inhibitors used in chemotherapy, we observed that Cdc7 inhibition causes selective cell death in tumor cell lines in a p53 independent manner while it causes a reversible cell cycle arrest in normal cells (Montagnoli, Tenca, Sola, Carpani, Brotherton, Albanese, and Santocanale, 2004). Furthermore it does not cause DNA damage, thus not increasing genomic instability, a feature that can lead to therapy resistance. Lack of DNA damage response and induction of apoptosis in cancer cells can...

Treatment General Management

If antiepileptic medications are prescribed, consideration must be given to potential interactions with other therapies, particularly chemotherapy. Some antiepileptic medications such as carbamazepine are inherently myelosuppres-sive and should be avoided when possible in this patient population. Some (e.g., phenytoin, carbamazepine, phenobarbital) induce the cytochrome p450 enzyme system in the liver. This alters the metabolization of some chemotherapy agents, and doses may need to be adjusted accordingly.

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