CHIBA, Japan—Combining either irinotecan(Drug information on irinotecan) (Camptosar) or vindesine(Drug information on vindesine) with cis-platin (Platinol) produced similar objective responses and survival rates in patients with stage IIIB or IV non–small-cell lung cancer, according to final results of a randomized trial.
Yuichi Takiguchi, MD, PhD, research associate in the Department of Chest Medicine, Chiba University School of Medicine, told ONI that differences in tumor response and survival seen with the two regimens were not statistically significant. The irinotecan/cisplatin combination had “a little bit higher response rate,” he said, but the survival rate with the vindesine regimen was slightly better. The irinotecan/cisplatin combination, he concluded, achieved results comparable to those with cisplatin(Drug information on cisplatin) and vindesine, a regimen previously shown to be active in advanced non–small-cell lung cancer.
Study Design
In the phase III trial conducted from June 1995 to October 1997, 104 patients were randomized to receive cisplatin 80 mg/m² on day 1 and irinotecan 60 mg/m² on days 1, 8, and 15 of 28-day cycles. The same dose of cisplatin was given to a comparative group of 106 patients on day 1 of a 28-day schedule along with 3 mg/m² vindesine on days 1, 8, and 15.
The two groups were well matched, Dr. Takiguchi reported. The median age being 62 in the irinotecan/cisplatin group and 64 in the vindesine/cisplatin group. Eligibility criteria for the study limited enrollment to patients with stages IIIB and IV non–small-cell lung cancer with no symptomatic brain metastases and no prior therapy. In all, 41% had stage IIIB disease and 59% stage IV. The ECOG performance status was 0-1 for 94% of the patients, and 2 for the remainder.
Evaluations for efficacy and toxicity were possible in 98 of the patients receiving the treatment that included irinotecan and in 101 of those given vindesine along with cisplatin, Dr. Takiguchi reported. Objective tumor responses were recorded for 28 of the patients receiving irinotecan and cisplatin (29%), compared with 22 of those receiving vindesine and cisplatin (22%).
Survival and Toxicity
Median survival was 45 weeks in the irinotecan group and 50 weeks in the vindesine cohort, Dr. Takiguchi said. One-year survival rates were 43% with irinotecan and 48% with vindesine, he added. The two-year survival rates were 14% and 20%, respectively.
The toxicity profiles did differ significantly, Dr. Takiguchi told ONI. “Cisplatin plus vindesine gave a higher incidence of neutropenia and leukopenia,” he said, “and CPT-11 [irinotecan] plus cisplatin showed a higher incidence of diarrhea.” Grade 4 neutropenia was seen in 50% of patients on the vindesine regimen, compared to 18% of those given irinotecan. Grades 3 and 4 diarrhea occurred in 13% of patients receiving irinotecan but only 1% of those given vindesine along with cisplatin. Two treatment-related deaths occurred with the irinotecan regimen.
The cisplatin/irinotecan combination will be studied in another trial planned by Japanese investigators, Dr. Takiguchi said. The multicenter study will assign patients to four different treatment regimens. The other three regimens to be tested are carboplatin(Drug information on carboplatin)/paclitaxel (Taxol), cisplatin/gemcitabine (Gemzar), and cisplatin/vinorelbine (Navelbine) combinations. The rationale for proceeding with further testing of the cisplatin/irinotecan regimen, Dr. Takiguchi explained, is based on the results of the study he described and another one reported at the conference by Takefumi Komiya, MD, of Kinki University School of Medicine, Osaka. The important point, Dr. Takiguchi stated, is that neither of these two studies showed the irinotecan/cisplatin combination to be inferior.
