Combination chemotherapy with irinotecan and cisplatin (IP) for advanced large-cell neuroendocrine carcinoma (LCNEC) of the lung: A multicenter phase II study.

Abstract

8037 Background: LCNEC and small cell lung cancer (SCLC) are recognized as high-grade neuroendocrine carcinoma of the lung. A differential diagnosis between LCNEC and SCLC using a tiny biopsy specimen is frequently difficult. Consequently, prospective clinical trials examining chemotherapy for advanced LCNEC have seldom been reported. We conducted a phase II study of combination chemotherapy with IP in patients (pts) with advanced LCNEC. Methods: The eligibility criteria included a chemotherapy-naïve status, a histological diagnosis of advanced LCNEC, an age of 20-75 years, and an ECOG PS of 0-1. Pts received I (60 mg/m2, days 1, 8, and 15) and P (60 mg/m2, day 1) every 4 weeks for up to 4 cycles. The primary endpoint was the response rate (RR). The sample size was determined to be 44, with a one-sided alpha of 0.1, a beta of 0.2, and expected and threshold values for the primary endpoint of 50% and 30%. Results: 44 pts from 11 institutes were enrolled between Jan 2005 and Nov 2011. The median age was 62.5 years; 21 pts had a PS of 0, and 35 pts were male. 5 pts had stage IIIB, 28 had stage IV, and 11 had recurrences after surgical resection. The RR was 54.5% (95% CI, 38.8-69.6). Grade 3 or 4 neutropenia was observed in 24 pts, but only 3 pts experienced febrile neutropenia. Other toxicities were mild and manageable. The median progression-free survival (PFS) was 5.9 months (95%CI, 5.5-6.3), and the median survival time (MST) was 15.1 months (95%CI, 11.2-19.0). Pathological specimens for a pre-planned central review were available for 41 pts. 30 pts were diagnosed as having LCNEC, whereas 10 pts were diagnosed as having SCLC, and 1 patient was diagnosed as having non-SCLC with a neuroendocrine morphology. Subgroup analyses were shown in the Table. Conclusions: Combination chemotherapy with IP was active in pts with advanced LCNEC, but the RR and the overall survival period in pts with LCNEC seemed to be inferior to those in pts with SCLC. Clinical trial information: UMIN000004796. [Table: see text]