Toxicity of concurrent chemoradiotherapy and consolidation chemotherapy with docetaxel and cisplatin in stage III non-small cell lung cancer:a phase I trial

Abstract

Objective To investigate the maximal tolerated dose (MTD) of docetaxel and cisplatin (DC) combined with concurrent radiation therapy (RT), and the appropriate interval between consolidation chemotherapy and concurrent chemoradiotherapy (CCRT) in patients with stage Ⅲ non-small cell lung canc-er (NSCLC). Methods A total dose of 60 -70 Gy was delivered to the primary tumor and positive lymph node regions in 30-35 fractions by three dimensional conformal RT. Chemotherapy regimen consisted of do-cetaxel and cisplatin, which were administered at the same dose. MTD was defined as the dose level at which ≥2/6 patients developed dose-limiting toxicity (DLT). Concurrent chemotherapy was administered on day 1 and day 28 of RT. The initial dose level was 55 mg/m 2 , then increased by 10 mg/m 2 each time until to 75 mg/m 2 . Consolidation chemotherapy at the same dose level was given 21 days per cycle for two cycles, which started 4, 5 or 6 weeks after RT. If ≥2/6 patients developed DLT during the consolidation chemo-therapy, The second cycle would be postponed for 1 week. Results All of the 12 patients who enrolled in the trial completed CCRT. Among them, 6 patients successfully received 2 cycles consolidation chemothera-py 4 weeks after the completion of RT. No DLTs occurred until the dose level reached 75 mg/m 2 . Two of three patients experienced DLT at the level of 75 mg/m 2 . Neutropenia was the main adverse effect. Conclu-sions In the treatment of stage Ⅲ NSCLC, a dose level of 65 mg/m 2 was recommended for phase Ⅱ study of CCRT and consolidation chemotherapy with docetaxei and cisplatin. Concurrent chemotherapy should be repeated every 4 weeks. Consolidation chemotherapy can be started 4 weeks after the completion of radiation and repeated every 3 weeks for 2 cycles. Key words: Neoplasm; non-small cell lung/radiotherapy; Neoplasm; non-small cell lung/chem-otherapy; Combined modality therapy; Clinical trial of Phase Ⅰ