OSAKA, JapanPatients with stage IV nonsmall-cell lung cancer randomized to a regimen of cisplatin(Drug information on cisplatin) (Platinol) and irinotecan(Drug information on irinotecan) (Camptosar) survived significantly longer than those receiving a cisplatin/vindesine combination in a phase III trial conducted in Japan.
In a final report on the trial, Takefumi Komiya, MD, assistant professor at Kinki University School of Medicine, Osaka, reported a subset analysis revealing a 14-week difference in median survivals for the regimens. The median survival among stage IV patients given cisplatin and irinotecan was 50 weeks, compared with 36.4 weeks for those treated with cisplatin and vindesine(Drug information on vindesine).
The three-arm trial, begun in July 1995, also tested therapy with irinotecan alone. All three regimens followed 28-day cycles. In the combination regimens, cisplatin 80 mg/m² was given on day 1 of the cycle. The other agents were administered on days 1, 8, and 15, irinotecan at 60 mg/m² and vindesine at 3 mg/m². When irinotecan was given alone, the dosage was 100 mg/m² administered on days 1, 8, and 15.
Between July 1995 and January 1998, 398 patients who had received no prior treatment for their nonsmall-cell lung cancer were enrolled in the multicenter trial. In all, 380 were assessable for survival and 373 for response and toxicity. Of the 380 patients included in the survival assessment, 37% had stage IIIB disease and 63% had stage IV disease. Performance status was 0-1 in 93% of these patients and 2 in 7%.
Survival Rates Vary
The 1-year survival rate among stage IV patients receiving irinotecan/cisplatin was 47.5%, significantly greater than the 26.3% for those receiving vindesine/cisplatin. Patients assigned to irinotecan alone had a median survival of 42.1 weeks and a 1-year survival rate of 37%.
Median survival overall was 50 weeks for the irinotecan/cisplatin combination, 45.6 weeks for vindesine/cisplatin and 46 weeks for irinotecan alone. One-year survival rates were 46.5% for irinotecan/cisplatin, 38.2% for vindesine/cisplatin and 41.8% for irinotecan. Two-year survival rates, Dr. Komiya reported, were 19% for the irinotecan/cisplatin group, 18% for the vindesine/cisplatin arm, and 21.9% for irinotecan alone.
Irinotecan alone, is not inferior to the older vindesine/cisplatin treatment, so it might be useful for some patients; for example, those who are poor risk, Dr. Komiya told ONI.
Grade 3 or 4 neutropenia was the major adverse reaction in all of the regimens. It was seen in 84.2% of the patients receiving vindesine/cisplatin and 70.6% of those receiving irinotecan/cisplatin. Neutropenia was seen less frequently with irinotecan alone, occurring in 25.6% of the patients in this treatment arm.
Severe diarrhea occurred in 15% of patients given only irinotecan, 11.9% of the irinotecan/cisplatin group, and 3.5% of the vindesine/cisplatin arm. Nausea and vomiting constituted a more frequent complaint among the irinotecan/cisplatin group, reported by 32.5% of these patients, compared to 22.5% of those given vindesine/cisplatin, and 9.4% of those receiving irinotecan only. Infection rates were 3.2% with irinotecan/cisplatin, 0.8% with vindesine/cisplatin, and 4.7% with irinotecan alone.