A combination of amrubicin and cisplatin was inferior to irinotecan and cisplatin in chemotherapy-naïve patients with extensive disease small-cell lung cancer (SCLC) in a phase III trial conducted in Japan.
A combination of amrubicin and cisplatin was inferior to irinotecan and cisplatin in chemotherapy-naÃ¯ve patients with extensive disease small-cell lung cancer (SCLC) in a phase III trial conducted in Japan. The irinotecan regimen remains the standard treatment for these patients in that country.
SCLC accounts for 13% of all new cases of lung cancer, and more than half of those patients present with extensive disease. Though SCLC can be very sensitive to chemotherapy, authors of the new study wrote that “rapid emergence of clinical drug resistance has resulted in poor prognosis, with almost all such patients dead with 2 years of initial diagnosis.” Investigators led by Miyako Satouchi, MD, PhD, of the Hyogo Cancer Center in Akashi, Japan, tested the amrubicin and cisplatin combination against irinotecan and cisplatin in 284 patients; results were published online ahead of print on March 17 in the Journal of Clinical Oncology.
A second interim analysis of the trial found that the hazard ratio (HR) for survival exceeded the noninferiority margin, and led to an early publication because of futility. The median survival time for the irinotecan group was 17.7 months, compared with 15 months for amrubicin, for an HR of 1.43 (95% CI, 1.10-1.85). Median progression-free survival was 5.6 months for irinotecan and 5.1 months for amrubicin, for an HR of 1.42 (95% CI, 1.16-1.73).
The response rates were not significantly different between the groups, at 72.3% for irinotecan and 77.9% for amrubicin (P = .33). With regard to toxicity, grade 4 neutropenia occurred in 22.5% in the irinotecan group and in 79.3% of the amrubicin group; grade 3 to 4 febrile neutropenia was also more common in the amrubicin group, at 32.1% vs 10.6%, while grade 3 to 4 diarrhea occurred in 7.7% of irinotecan patients and in 1.4% of amrubicin patients.
“Considering that hematoxicity and [febrile neutropenia], even after reduction of the dose… were relatively serious, and considering the excellent effect of amrubicin monotherapy in relapse treatment, we are unable to recommend [amrubicin and cisplatin] as standard first-line therapy for extensive-disease SCLC,” the authors concluded. “[Irinotecan and cisplatin] therapy showed favorable OS and toxicity profile, indicating, as expected, its continuing presence as one of the standard first-line therapies.”
The amrubicin group received the study drug in a dose of 40 mg/m2 on days 1–3, and cisplatin 60 mg/m2 on day 1 every 3 weeks. The control group received irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin on day 1 every 4 weeks. More than 83% of patients in both groups were male, and both groups had a median age of 63 years. In both groups, 97.9% of patients were smokers.