Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer

Purpose Etoposide and cisplatin (EP) has been a standard treatment for extensive-disease small-cell lung cancer (SCLC). An earlier phase III trial reported improved survival for patients receiving irinotecan plus cisplatin (IP) versus EP. Our trial was designed to determine if a modified weekly regimen of IP would provide superior survival with less toxicity than EP. Patients and Methods The primary objective was to compare overall survival in extensive-disease SCLC patients randomly assigned to receive IP (n=221) or EP (n=110). Patients were randomly assigned in 2:1 ratio to cisplatin 30 mg/m(2) intravenously (IV) + irinotecan 65 mg/m(2) IV on days 1 and 8 every 21 days, or cisplatin 60 mg/m(2) IV on day 1, and etoposide 120 mg/m(2) IV on days 1 to 3 every 21 days for at least four cycles, until progressive disease, or until intolerable toxicity resulted. Results Selected grade 3/4 toxicities for IP/EP were: neutropenia (36.2% v 86.5%; P<.01), febrile neutropenia (3.7% v 10.4%; P=.06), anemia (4.8% v 11.5%; P=.02), thrombocytopenia (4.3% v 19.2%; P<.01),. vomiting (12.5% v 3.8%; P=.04), and diarrhea (21.3% v 0%; P<.01). There was no significant difference in response rates (48% v 43.6%), median time to progression (4.1 v 4.6 months), or overall survival (median survival time, 9.3 months v 10.2 months; P=.74). Conclusion Treatment with this dose and schedule of IP did not result in improved survival when compared with EP. Fewer patients receiving IP had grade 3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with patients receiving EP, but more had grade 3/4 diarrhea and vomiting.