Fractionated Administration of Irinotecan and Cisplatin in Japanese Patients With Extensive-Stage–Disease Small-Cell Lung Cancer

Abstract

TO THE EDITOR: We read with great interest the recent article by Hanna et al, in which they reported irinotecan and cisplatin (IP) regimen was not superior to the etoposide and cisplatin (EP) regimen for extensive-stage–disease (ED) small-cell lung cancer (SCLC), even though Noda et al clearly showed the superiority of IP regimen over EP regimen. We previously fractionated the schedule of IP to obtain the synergistic effect of the two drugs and to reduce toxicities. The recommended doses of irinotecan and cisplatin on days 1 and 8 were determined to be 50 mg/m and 60 mg/m, respectively. However, the phase II study for ED SCLC was stopped early because of poor outcomes in the interim analysis. Despite the small number of patients in our study, the median survival time and 1-year survival rates were similar to those reported in the study by Hanna et al (Table 1). The delivered doses of irinotecan and cisplatin in their study were 1.8 times and 0.7 times as much as those of our study, respectively (Table 1). In comparison to the study by Noda et al, we should have modified fractionated administration by escalating the dose of irinotecan and reducing that of cisplatin to improve the outcomes. However, both irinotecan and cisplatin in the Hanna et al study showed more dose intensity than that reported in the Noda et al study. Hanna et al suggested that IP might therefore be a better regimen for Japanese patients. We considered fractionated administrations of IP to be inferior to the original schedules of IP (cisplatin on day 1 and irinotecan on days 1, 8, and 15) for not only American but also Japanese patients with ED SCLC based on the findings of our study. Another explanation for the negative results of the Hanna et al study might be due to salvage chemotherapy. More patients on the IP arm received subsequent treatment with etoposide (47.2% v 22.6%) whereas more patients on the EP arm received subsequent treatment with topoisomerase I inhibitors including irinotecan or topotecan (33% v 24.1%). Noda et al did not describe the use of salvage chemotherapy, which might have affected the survival difference in both arms. Because chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI), followed by fluorouracil, leucovorin, and oxaliplatin (FOLFOX), had almost the same efficacy as that with FOLFOX followed by FOLFIRI in the treatment of advanced colorectal cancer, IP followed by EP might therefore have had the same efficacy as EP followed by IP in the treatment of ED SCLC. To achieve a prolonged survival, the administration of all three active cytotoxic drugs (cisplatin, irinotecan, and etoposide) during the treatment course may thus be necessary.