Irinotecan therapy for small-cell lung cancer.
The DNA topoisomerase inhibitor irinotecan (CPT-11, Camptosar) is being evaluated as a novel chemotherapeutic agent that may complement other agents and treatment modalities for small-cell lung cancer (SCLC). Combination chemotherapy is the most effective means of improving the survival of patients with extensive disease, but until recently, no combination demonstrated superior efficacy. In a recent Japanese phase III study, irinotecan in combination with cisplatin significantly improved the survival of previously untreated patients with extensive SCLC compared to standard etoposide/cisplatin therapy (median progression-free survival: 6.9 vs 4.8 months, P = .003; median overall survival: 12.8 vs 9.4 months, P = .002). Two additional phase III trials have been planned in the United States to confirm these results, and to investigate how the administration schedule of irinotecan/cisplatin may be modified to improve its therapeutic index. The results of phase I/II studies have shown that other irinotecan-based combinations demonstrate promising activity in this disease as both first- and second-line therapy. This article reviews the rationale for the use of irinotecan in SCLC, examines key findings from recent clinical studies of irinotecan-based therapy, and discusses how the use of irinotecan in combination with new noncytotoxic anticancer agents can and will be further explored.
Sandler
Alan
A
Vanderbilt University, Medical Center, Nashville, Tennessee 37232, USA.
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D016019:Survival Analysis; D059004:Topoisomerase I Inhibitors; D014481:United States
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin