Phase II trial of 21-day regimen of irinotecan and carboplatin for chemonaive or relapsed small-cell lung cancer: Long-term survival

Abstract

19009 Background: The regimen of irinotecan and platinum is a promising treatment for metastatic small-cell lung cancer (SCLC) (Noda et al. NEJM, 346:85, 2002). We conducted a multi-institution trial to evaluate the efficacy and toxicity of a novel 21-day schedule of irinotecan and carboplatin in chemonaive patients with extensive SCLC (arm A) and previously chemotherapy-treated patients with relapsed SCLC (arm B). We are updating long-term survival data 5 years after initiation of the trial. Methods: According to a 2-stage phase II design, 80 patients (40 in arm A and 40 in arm B) have been enrolled with the following characteristics: male/female, 39/41; median age, 65 years; performance status (PS), 0–1 (85%), 2 (15%). Dosing schemas were based on population-based maximum tolerated doses determined in a previous intrapatient dose-escalation trial at our institution (Wild et al. Oncology 17:11–16, 2003). Chemonaive patients with extensive disease (arm A) were treated with irinotecan 200 mg/m2 and carboplatin AUC of 5; while patients with previously chemotherapy-treated and relapsed disease (arm B) received irinotecan 150 mg/m2 and carboplatin AUC of 5, every 21 days for 6 cycles. Results: The most common grade 3/4 toxicities are presented in the Table. Among 69 assessable patients, response rates of 69% and 49% were observed for arm A and arm B, respectively. By intent-to-treat Kaplan-Meier analysis, the median survival is 10 months for both Arm A and B. 1-year and 2-year survivals are 35.0% and 12.5% for Arm A and 30.3% and 11.4% for Arm B, respectively. Conclusions: This 21-day regimen of irinotecan and carboplatin is feasible and particularly promising for treatment of relapsed SCLC. Growth factor support with G-CSF is recommended with the regimen. (Supported by Pfizer Inc. and NCI K24CA10014) Toxicity Arm A (%) N = 37 Arm B (%) N = 33 Total (%) N = 70 Neutropenia 19 (51) 16 (48) 35 (50) Thrombocytopenia 8 (22) 5 (15) 13 (19) Anemia 4 (11) 4 (12) 8 (11) Diarrhea 9 (24) 5 (15) 14 (20) Nausea/emesis 3 (8) 5 (15) 8 (11) Treatment death 2 (5) 1 (3) 3 (4) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology