Survival Benefit Seen With Irinotecan/Cisplatin in Metastatic Non–Small-Cell Lung Cancer

OSAKASAYAMA, Japan—Irinotecan (Camptosar) plus cisplatin (Platinol) significantly improves survival, compared to vindesine/cisplatin, in patients with metastatic non–small-cell lung cancer (NSCLC), according to an analysis of two studies presented by Masahiro Fukuoka, MD, of Kinki University School of Medicine, Osakasayama, Japan, at a poster session at the American Society of Clinical Oncology (ASCO) annual meeting.

The irinotecan/cisplatin regimen showed an estimated average decrease of 33% in the risk of death, according to the report.

The results were based upon data obtained from two randomized phase III trials in advanced NSCLC presented at the ASCO annual meeting in 1999.

Investigators examined the effect of the irinotecan/cisplatin regimen on survival in metastatic NSCLC by performing a multivariate analysis of the data from the two randomized phase III trials using a Cox regression model. The Japanese team demonstrated survival benefits with the irinotecan/cisplatin regimen.

“This is certainly suggestive of a benefit,” Alan Sandler, MD, of Vanderbilt University Medical Center, said in an ONI interview. “I think CPT-11 [irinotecan] is an interesting drug and may well have activity in this setting.”

From June 1995 to January 1998, the Japanese group ran two similarly designed randomized phase III trials. Study A compared irinotecan/cisplatin with vindesine/cisplatin. The study also compared irinotecan/cisplatin with irinotecan alone. Study B compared irinotecan/cisplatin with vindesine/cisplatin.

The two studies included 358 eligible patients with stage IV disease: 139 patients receiving irinotecan/cisplatin, 134 patients receiving vindesine/cisplatin, and 85 patients receiving irinotecan. Patients were stratified according to performance status (0-1 vs 2), stage (IIIB vs IV), and study institution.

Dosages were identical in both studies. Patients in the irinotecan/cisplatin arms received cisplatin 80 mg/m² on day 1 and irinotecan 60 mg/m² on days 1, 8, and 15 every 4 weeks. Patients in the vindesine/cisplatin arms received cisplatin 80 mg/m² on day 1 and vindesine 3 mg/m² on days 1, 8, and 15 every 4 weeks. Patients receiving irinotecan alone received irinotecan 100 mg/m² on days 1, 8, and 15 every 4 weeks.

Results from study A, the three-arm study, show the following response rates for stage IV patients: 43.6%, 27.0%, and 14.5% among the patients receiving irinotecan/cisplatin, vindesine/cisplatin, and irinotecan alone, respectively.

Results from study B, the two-arm study, show the following response rates for stage IV patients: 27.1% and 29.3% among the patients receiving irinotecan/cis-platin and vindesine/cisplatin, respectively.

Analysis of patients at lowest risk revealed a median survival of 124.9 weeks for patients receiving irinotecan/cisplatin and 85.0 weeks for patients receiving vindesine/cisplatin.

In patients at highest risk, median survival time was 20.3 weeks for those patients receiving the irinotecan/cisplatin regimen and 16.7 weeks for the vindesine/cisplatin regimen.

According to Dr. Fukuoka, analysis of these two studies suggest that the irinotecan/cisplatin regimen significantly improves survival, compared with the vindesine combination (P = .0043). He concluded that further studies are needed to demonstrate whether irinotecan plus cisplatin improves survival in comparison with other promising new combination regimens.