As with salivary gland tumors, thyroid cancer constitutes a spectrum of histologic subtypes and clinical
Table 22-10. COMBINATION CHEMOTHERAPY IN SALIVARY GLAND CANCER
No. of Patients
Overall Response Rates (%)
CDDP/5-FU CDDP/DOXO/5-FU CDDP/EPI/5-FU or CTX CTX/DOXO CTX/DOXO/CDDP
Adenoid cystic Mucoepidermoid Mucoepidermoid 'Variable 'Variable 'Variable 'Variable
25 33 33 35 45 45 50
* Variable: includes adenoid cystic carcinoma and mucoepidermoid carcinoma as the most common histologies.
BLM = bleomycin; CDDP = cisplatin; CT = chemotherapy; CTX = cyclophosphamide; DOXO = doxorubicin; 5-FU = 5-fluorouracil; EPI :
methotrexate; VCR = vincristine.
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 sumption of an iodine-rich diet, inadequate levels of thyroid stimulating hormone (TSH), or persistence of a significant amount of native thyroid cancer may all affect the efficacy of RAI treatment for the tumor. For RAI-refractory disease, initial observation is appropriate for selected patients, as the tumor may grow slowly. If chemotherapy is indicated, doxorubicin is the most studied and widely used drug, with response rates in the 30 to 40 percent range.148,149 Cisplatin, carboplatin, methotrexate, and etoposide also have activity.150 Combination chemotherapy may improve response rate but has unproven benefit in terms of palliation and survival. Chemotherapy and radiation have been combined for the treatment of compelling local disease with good local effect in most patients.151152 The possible use of agents intended to
differentiate the tumor (eg, retinoids) and help it regain RAI avidity is an area of active interest.153
Anaplastic thyroid cancer is an aggressive subtype with a poor prognosis even with the best available therapy. Generally these tumors are unresectable at presentation and are not RAI avid. Combined modality chemotherapy/radiation programs 151,152 are commonly employed initially in the management of these cancers with reported improvement compared to historical results with radiation alone. There are, however, no randomized data, and survival statistics remain disappointing. When chemotherapy is employed alone, one randomized trial reported a higher complete response when doxorubicin and cisplatin were combined compared to doxorubicin alone.154 Of note, a large cell lymphoma of the thyroid can present in a manner similar to anaplastic thyroid cancer, but the former will have a better prognosis and chemotherapy for the disease is much more effective. Accordingly, the initial pathology review is extremely important.
Medullary carcinoma is another cancer that can behave in an indolent manner, where initial observation in order to get a sense of disease trajectory is often a good option for the patient. Streptozocin, cyclophosphamide, dacarbazine, and 5-fluorouracil appear to have some activity, alone or in combination, but only a minority of patients will have a major response.155,156 Many of these patients will suffer from troublesome diarrhea for which debulk-ing of gross tumor or a trial of octreotide or inter-feron-a may be helpful.157,158 Occasionally these patients will present to the medical oncologist without appropriate screening studies having been done to rule out a familial syndrome. If so, an appropriate screening evaluation should be initiated.
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