OSAKA, Japan-A randomized phase III trial in small-cell lung cancer patients with extensive disease was stopped after interim analyses uncovered a clear survival benefit for a regimen combining irinotecan (Camptosar) and cisplatin (Platinol) over an etoposide (VePesid) and cisplatin combination.
OSAKA, JapanA randomized phase III trial in small-cell lung cancer patients with extensive disease was stopped after interim analyses uncovered a clear survival benefit for a regimen combining irinotecan (Camptosar) and cisplatin (Platinol) over an etoposide (VePesid) and cisplatin combination.
Conducted by the Japan Clinical Oncology Group (JCOG), the study was designed to accrue 230 patients. At the time the trial was halted in November 1998, 154 patients had been enrolled and treated since November 1995, reported Shunichi Negoro, MD. Dr. Negoro heads the Department of Pulmonary Medicine and Oncology at Osaka City General Hospital.
On the basis of the first interim analysis performed in August 1998 when half the patients had been accrued, the independent monitoring committee recommended doing the second analysis earlier than planned because of the large difference in survival, Dr. Negoro explained. When the second analysis was completed, he said, the committee recommended termination due to the significant difference. The P value, he noted, was .00025.
Median Survival Prolonged
Since then, mature data analyzed in March 2000 have shown that median survival was prolonged by approximately 40% by the irinotecan/cis-platin combination as compared to the etoposide/cisplatin regimen, Dr. Negoro reported.
The median survival was 390 days with irinotecan/cisplatin and 287 days with etoposide/cis-platin, he noted. The 1-year survival rate was 58% for the irinotecan/cisplatin cohort and 38% for the etoposide/cisplatin group. In the irinotecan/cis-platin arm of the study, the 2-year survival rate was 19%, compared with 7% among patients receiving the etoposide/cisplatin regimen.
The median progression-free survival with irinotecan/cis-platin was 209 days, Dr. Negoro reported, compared to 145 days with etoposide/cisplatin. Objective response rates also differed83% with irinotecan/cisplatin and 68% with etoposide/cisplatin.
The protocol called for patients in one arm of the trial to receive irinotecan 60 mg/m² on days 1, 8, and 15 and cisplatin 60 mg/m² on day 1 of each 4-week cycle. In the comparative arm, the dosage schedule was etoposide 100 mg/m² on days 1, 2, and 3 and cisplatin 80 mg/m² on day 1 of each 3-week cycle. Four treatment cycles were planned for both groups.
Each arm of the study included 77 patients, with no significant differences in their characteristics. The median age in both, for example, was 63 years. The number of patients who were delivered all four courses of chemotherapy was similar at about 70% observed Dr. Negoro. The number of patients who required no dose or schedule modification, he reported, was somewhat higher in the etoposide/cisplatin arm.
Myleosuppression was the most frequent toxicity encountered in both arms, Dr. Negoro said. JCOG Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia all occurred more often with etoposide/cisplatin than with irinotecan/cisplatin, he noted. The comparative rates for leukopenia were 52% and 27%, for neutropenia 92% and 66%, and for thrombocytopenia 18% and 5%. Grade 3 and 4 diarrhea complicated the course of 16% of the patients receiving the irinotecan/cisplatin combination but none of those given etoposide and cisplatin. No other significant differences in nonhematologic toxicities were seen.
Its an impressive study, commented James R. Jett, MD, consultant in pulmonary and critical care medicine and medical oncology, Mayo Clinic, Rochester, Minnesota, but it must be confirmed by other groups. One such trial, he indicated, will be conducted by the Southwest Oncology Group in the United States. He expressed hope for confirmation because that would be one of the biggest advances in small- cell lung cancer that we have seen in recent years.
In the Japan Clinical Oncology Group, Dr. Negoro noted, he and his colleagues already consider irinotecan with cisplatin as the new standard regimen against extensive disease small-cell lung cancer.