Induction chemotherapy with carboplatin (C), paclitaxel (P) and gemcitabine (G) in unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC). A phase I-II study

Abstract

7592 Background: The addition of G to doublet chemotherapy with C and P has demonstrated improvement in overall response rate in stage IIIB and stage IV NSCLC with increased hematologic toxicity. Aim of the study was to evaluate safety and efficacy of a triplet induction (ind) chemotherapy followed by concomitant (conc) chemo-radiotherapy with CPG in clinically unresectable stage IIIA or IIIB NSCLC patients (pts) suitable for radical radiation treatment. Methods: In a phase I-II study, pts with histologically confirmed NSCLC, aged 18- 75, ECOG PS 0–1, adequate organ function, no prior chemotherapy, received 3 cycles of CPGind at two dose levels (see table). Pts with responding or stable disease received CPGcon (C AUC 2 day 1, P 40 mg/m2 day 1, G 225 mg/m2 day 4, every 7 days). Surgery was allowed for stage IIIA disease responsive to CPGind. Results: Nineteen pts were treated, 16 were evaluable for toxicity and response, 12 males and 4 females, median age 56 (range, 39–74), PS 0/1 (11/5 pts), stage IIIA/IIIB (9/7 pts). Dose limiting toxicities (DLTs) are reported in the table. No toxic death and febrile neutropenia were observed. Seven out of 8 assessable pts did not complete CPGcon, mainly due to grade 3 mucositis (7 pts) and haematological toxicity (5 pts). Following CPGind, 12 pts (75%) had a partial response, 3 stable disease, 1 pt disease progression. Four out of 8 assessable pts (50%) with stage IIIA disease underwent surgery. Conclusions: CPGind is feasible at the first dose level, although associated with significant haematological toxicity, and produces high response and resectability rates. It is unlikely to be followed by CPGcon, so it should be considered for future studies in unresectable stage IIIA disease Dose levels and DLTs Dose level Pts DLTs Grade 3 DLT Grade 4 DLT Level 1 11 5 neutropenia (3 pts), thrombocytopenia (1 pt), anemia (1 pt) acute myocardial infarction (1 pt), neutropenia (1 pt) C AUC5 d1 P 175 mg/m2 d1 G 800 mg/m2 d1,8 (q21) Level 2 5 3 AST/ALT (1 pt), asthenia (1 pt), neutropenia (1 pt) - C AUC6 d1 P 200 mg/m2 d1 G 1,000 mg/m2 d1,8(q21) No significant financial relationships to disclose.