SCLC typically presents as extensive disease (approximately 60-70% of new cases) and progresses very quickly. Small cell carcinomas are very responsive to chemotherapy and radiation, but have a short duration of response. Radiotherapy became the standard in 1969, when a randomized trial showed that it offered the potential for
cure, whereas surgery did not. In the vast majority of patients, chemotherapy with or without radiotherapy is the treatment of choice. Even after a complete response to therapy, the cancer usually recurs within 6 to 8 months, and survival time following recurrence is typically short (approximately 4 months). This yields a typical survival
rate of 14 to 20 months for limited disease and 8 to 13 months for extensive disease. Figure 90-2 illustrates the general treatment path of SCLC.
The regimen of choice for limited-disease SCLC is etoposide-cisplatin (EP). In patients who are able to tolerate combined therapy, concomitant chemoradiotherapy offers the greatest survival benefit. Carboplatin may be substituted for cisplatin in pa-
tients who cannot tolerate cisplatin toxicity. In European countries, a three-drug combination containing an anthracycline has been the mainstay of therapy; however, mounting clinical evidence shows that these regimens are inferior to EP plus concurrent radiation and have more toxicity. Consequently, the guidelines recommend that
the EP regimen be used with concurrent radiotherapy.
Because patients with SCLC commonly have a recurrence in the CNS, trials have been performed to evaluate the benefit of PCI. A pivotal study showed that PCI reduces the incidence of brain metastasis and increases 3-year survival from 15% to
21%. Patients with limited stage SCLC who achieve a complete response with treatment should be offered PCI.
Platinum regimens, particularly EP, are the treatment of choice in extensive disease. In one Japanese study, a combination of irinotecan and cisplatin demonstrated an increased median survival time by approximately 3 months over the EP regimen. This irinotecan-cisplatin regimen also had a lower incidence of severe neutropenic side ef-
fects but exhibited higher rates of middle- to high-grade diarrhea. However, this study was repeated in the United States and did not show a similar improvement over the EP regimen.40 Therefore, EP remains the regimen of choice for treating extensive SCLC in the United States. Due to the high sensitivity of treatment-naive SCLC to chemotherapy, it is imperative that these patients be monitored for signs of tumor lysis syndrome and possibly treated with prophylactic therapy.
Concurrent radiotherapy is not used routinely in extensive disease; however, PCI provides significant benefit in patients responding to chemotherapy. A pivotal study demonstrated that median survival from the time of randomization increased from 5.4 to 6.7 months and 1-year survival rates increased from 13.3% to 27.1% with PCI. An additional benefit was a lower rate of brain metastasis (14.6% versus 40/0/Nl 41
The treatment of recurrent SCLC depends on the time to recurrence. If the time to recurrence is less than 6 months, second-line therapy should be considered if the patient has an acceptable PS (see Patient Care and Monitoring). The most widely accepted second-line therapies in SCLC are topotecan alone or CAV [cyclophosphamide, doxorubicin (Adriamycin), and vincristine]. Relapses occurring more than 6 months after treatment warrant a repeat of the initial regimen. Poor PS patients (3-4) are typically treated with palliative care therapies.
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