Phase I/II Study of Induction Chemotherapy of Carboplatin and Irinotecan Followed By Sequential Thoracic Radiotherapy (Trt) for Elderly Patients with Limited-Stage Small-Cell Lung Cancer (Ld-Sclc): Torg 0604

Aim: The effect of irinotecan in treatments for LD-SCLC in the elderly is unclear, and the optimal timing of TRT when combined with chemotherapy has not been fully evaluated. We report a phase I/II trial of induction chemotherapy with carboplatin and irinotecan followed by sequential TRT in this population? Methods: Patients with untreated, measurable LD-SCLC >70 years with performance status (PS) 0 to 2 and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8 every 21 days for four cycles. TRT of 54Gy in 27 fractions was then administered sequentially. Carboplatin dose was escalated from AUC of 4 to 5 (Levels 1 and 2, respectively)?with a fixed dose of irinotecan at 50 mg/m2. The primary objective of the phase II portion was evaluation of efficacy. Results: A total of 41 patients were enrolled [median age 75 years, range 70-86 years; 31 male, 10 female; PS 0/1/2: 22/18/1]. At Level 1 (n=6), one patient experienced dose-limiting toxicity (DLT) as Grade 3 hypertension. At Level 2 (n=6), two patients experienced DLT as Grade 4 thrombocytopenia. Therefore, level 1 was chosen as the recommended dose. The phase II trial was then expanded by 35 patients in the level 1 based on the Simon minimax design. In all cohorts, the median chemotherapy cycle was 4 (1/2/3/4 courses administered as 4/2/2/33); median radiation dose was 54Gy (range 36-60). Toxicities were generally mild, as expected.?Gr 3/4 leukopenia and thrombocytopenia were both observed in six (15%) patients. No Gr 3/4 diarrhea or esophagitis was noted. Although Gr 3 febrile neutropenia and Gr 3 pneumonitis were seen in two patients each, no treatment-related deaths occurred. There were five complete responses and 32 partial responses, for a response rate of 90%. With median follow-up of 80.4 months (n=41), median progression-free and overall survival times were 12.4 and 27.1 months, respectively. Conclusions: Induction chemotherapy with carboplatin plus irinotecan followed by sequential TRT was well tolerated and highly active in elderly patients with LD-SCLC. Further confirmatory studies are warranted. Disclosure: All authors have declared no conflicts of interest.