Phase II study of consolidation amrubicin after concurrent chemoradiotherapy for patients with limited-stage small cell lung cancer.

Abstract

8555 Background: Concurrent chemoradiotherapy (CCRT) using etoposide and cisplatin has been the gold standard for limited-stage small-cell lung cancer (LS-SCLC) for decades; however, approximately three out of four cases treated by CCRT inevitably relapse. Amrubicin (AMR), a synthetic anthracycline with a structure similar to doxorubicin, has demonstrated strong antitumor activity against relapsed SCLC and has been the standard second-line treatment for SCLC in Japan. We consider consolidation AMR following CCRT to be a potential treatment for patients with LS-SCLC. Methods: In this single-arm, multicenter phase II study, all patients enrolled were treated using induction CCRT consisting of four cycles of etoposide at 100 mg/m2 on days 1-3 and cisplatin at 60 mg/m2 on day 1 every 3 weeks, plus concurrent thoracic radiotherapy (1.5 Gy twice daily, total 45 Gy) concomitant with the first cycle of chemotherapy. Then, eligible patients received three cycles of AMR at 40 mg/m2 on days 1-3 every 3 weeks as consolidation treatment. The primary endpoint was the 2-year progression-free survival (PFS) rate in patients who received consolidation AMR, and the secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), and safety. This study was terminated early due to slow patient accrual. Results: Of the 36 patients who underwent induction CCRT (ITT population), 28 (78%) received AMR as consolidation therapy (consolidation population) and 24 (67%) completed all planned treatments. The 2-year PFS rate and ORR were 35.7% and 86% (8 CR and 16 PR), respectively, in the consolidation population. The median PFS and median OS were 14.3 months (95%CI, 10.8-46.6) and 60.9 months (95%CI, 29.8-NR), respectively, in the consolidation population. In the ITT population, the median PFS and the median OS were 13.4 months (95%CI, 7.5-19.0) and 60.9 months (95%CI, 29.8-NR), respectively. Grade 3/4 toxicities during the consolidation phase included neutropenia (39%), thrombocytopenia (14%), and febrile neutropenia (7%). There were no treatment-related deaths in the ITT population. Conclusions: Consolidation AMR following standard CCRT consisting of etoposide and cisplatin plus concurrent thoracic radiotherapy was feasible, and demonstrated promising efficacy for LS-SCLC. Clinical trial information: 000002352.