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
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