Irinotecan: future directions in small-cell lung cancer

Small-cell lung cancer (SCLC) accounts for approximately 20%-25% of all cases of lung cancer and has an especially poor prognosis, resulting in about 25% of all lung cancer deaths. About two thirds of patients with SCLC will present with more advanced and less treatment-sensitive extensive disease (ED). Five-year survival is negligible for patients with ED. Combination chemotherapy is the most effective treatment modality for SCLC. For patients with ED SCLC, chemotherapy can increase median survival from about 1.5 months to 7-11 months, with 2-year survival uncommon. Several new agents, including carboplatin, ifosfamide, and the taxanes, have been shown to be active against SCLC but have not resulted in improvement in overall survival. Among the most active to date has been the topoisomerase I inhibitor, irinotecan. A recent phase III study of the combination of irinotecan/cisplatin indicates improved survival over cisplatin/ etoposide. Survival results indicate that overall survival with irinotecan/cisplatin was significantly better than the standard treatment arm (12.8 months vs. 9.4 months, P = 0.0021, unadjusted one-sided log-rank test). These results represent a major advance and, if confirmed, may establish this regimen as the new standard of care for ED SCLC. These future directions will include the confirmation of the Japanese phase III trial in ED SCLC, evaluating the role of irinotecan in limited-stage disease, new doublet and triplet combinations containing irinotecan, and evaluation of irinotecan combinations with the newer molecularly targeted agents (ie, SU5416).