Lung Cancer Health Center
Extensive-Stage Small Cell Lung Cancer
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
As in limited-stage (LD) small cell lung cancer (SCLC), chemotherapy is commonly given as a two-drug combination of platinum and etoposide in doses associated with at least moderate toxic effects in patients with extensive-stage disease (ED). Doses and schedules used in current programs yield overall response rates of 50% to 80% and complete response rates of 0% to 30% in patients with ED.[1,2][Level of evidence: 1iiA] Two meta-analyses have been published evaluating the role of cisplatin and/or carboplatin or the platinum combinations. However, a Cochrane analysis did not identify a difference in 6-, 12-, or 24-month survival.[3] A meta-analysis of 19 trials published between 1981 and 1999 showed a significant survival advantage for patients receiving platinum-based chemotherapy compared with those not receiving a platinum agent.[2][Level of evidence: 1iiA]
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Cisplatin is associated with significant toxic effects and requires fluid hydration, which can be problematic in patients with cardiovascular disease. Carboplatin is active in SCLC, is dosed according to renal function, and is associated with less nonhematological toxic effects. The Hellenic Oncology Group conducted a phase III trial comparing cisplatin and etoposide with carboplatin plus etoposide.[4] The median survival was 11.8 months in the cisplatin arm and 12.5 months in carboplatin-treated patients.[4][Level of evidence: 1iiA] Although this difference was not statistically significant, the trial was underpowered to prove equivalence of the two treatment regimens in patients with either LD or ED. The platinum combination of cisplatin and etoposide remains the most commonly used regimen.[5]
The substitution of irinotecan for etoposide has yielded conflicting results. A phase III study conducted in Japan compared a standard two-drug regimen of cisplatin and etoposide with a combination of cisplatin and irinotecan.[6][Level of evidence: 1iiA] The planned enrollment was 230 patients younger than 70 years, however, the trial was stopped early with a total of 154 patients when an interim analysis found a significant difference favoring the irinotecan arm. The median survival in the cisplatin and irinotecan group was 12.8 months (95% confidence interval [CI], 11.7-15.2 months) while it was 9.4 months in the cisplatin and etoposide arm (95% CI, 8.1-10.8 months). The 2-year survival was 19.5% versus 5.2%. Hematologic toxic effects were more severe in the etoposide- and cisplatin-treated patients, while gastrointestinal toxic effects were worse in the irinotecan-treated and cisplatin-treated patients. However, no difference in response rate, median time-to-progression, or overall survival (OS) was reported from a second study that involved 331 patients with ED and compared cisplatin and etoposide with a modified weekly regimen of cisplatin and irinotecan.[7] Phase III studies, including SWOG-S0124 (NCT00045162), of cisplatin or carboplatin with etoposide versus platinum and irinotecan have been conducted.[7,8]
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