P2-177: A multicenter phase II study of carboplatin plus gemcitabine followed by concomitant chemoradiation in patients with non-resectable stage III non-small-cell-lung cancer: preliminary report of the Cher@Nos trial

Combined chemoradiotherapy is now considered the standard of care in patients with unresectable stage III NSCLC. Despite the therapeutic advances that have been made during the last decennium, there remains a need for better local and distal control of disease in patients with locally advanced NSCLC. At present it is not clear which combined modality approach provides optimal results (both in terms of survival and toxicity). In the present study we wanted to evaluate whether by combining a carboplatin-gemcitabine based induction chemotherapy with weekly cisplatin during standard thoracic radiotherapy, it is possible to obtain good efficacy with minimal toxicity Patients (PS 0-1) with unresectable stage III NSCLC were treated with 3 cycles of induction chemotherapy followed by chemo-radiotherapy. The induction chemotherapy consisted of carboplatin (AUC 5 on day 1) with gemcitabine (1200 mg/m2 on day 1 and 8) every 3 weeks for 3 cycles. The chemo-radiotherapy consisted of cisplatin (30 mg/m2 weekly) concomitant with conventional radiotherapy (2.0 Gy/fraction, 5 fractions a week, up to a total dose of 60 Gy). The primary endpoint of this phase II trial was a survival rate at 2 years of >35%. Between February 2003 and November 2005, 45 patients were enrolled: The demographics were as follows: 34/11 male/female, 14/30 stage IIIA/IIIB, median age 62 y (range 41-81 y), 42% squamous cell and 33% adenocarcinoma. All patients received at least one cycle of induction chemotherapy: 7% only 1 cycle, 7% 2 cycles and 87% all 3 cycles. Chemoradiotherapy was started in 36 patients. Median total radiation dose and duration was 60 Gy and 43 days. Grade 3/4 toxicities during chemotherapy were: neutropenia (36%), thrombocytopenia (18%), febrile neutropenia (1%), rash (1%), elevation of transaminases (1%) and constipation (1%). The effect of the treatment on the pulmonary function is summarized in the folowing table: TableBaselinePost-chemoPost-chemoradioFollow-up at 6 monthsFollow-up at 12 monthsMean FEV1 (L)2.262.422.482.332.27Mean FVC (L)3.193.413.143.323.05Mean DLCO (%)67.760.460.764.265.4 Open table in a new tab The overall response rate was 31% (2% CR, 29% PR) following induction chemotherapy, and 58% (2% CR, 56% PR) at the end of treatment. With a median follow-up of 14.4 months (range 1-35 months), the median progression-free survival is 10.6 months. The overall 1- and 2-year survivals are 61% and 39%. The preliminary results from this phase II trial showed that induction chemotherapy with carboplatin and gemcitabine followed by thoracic radiotherapy with concurrent weekly cisplatin is a well tolerated combined modality approach with promising overall survival in patients with unresectable stage III NSCLC.