e20067 Background: Platinum-based CChRT is recommended as the evidence-based approach for the management of patients (p) with locally advanced stage III NSCLC and a good performance status, although a clearly superior regimen has not been identified. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with Cisplatin (C) and intravenous and oral vinorelbine (V) and thoracic radiotherapy. Methods: 39 p with histologically confirmed inoperable locally advanced NSCLC, stage IIIA (T4 or N2)/IIIB, PS 0-1 and adequate lung function (FEV1 > 1.1, V20 < 30%) were included in CChRT with: C 80 mg/m2 day 1 and intravenous V 25 mg/m2 day 1 and oral V 60 mg/m2 day 8 for three cycles, during conformal radical thoracic radiotherapy (66 Gys, 180 cGy/day). The primary objective was overall survival (OS); secondary objectives were progression free survival (PFS), response rate (RR) and toxicity. Median follow-up: 20,4 months. Results: The p characteristics were: mean age 69,8 years (44-75); male/female: 33/6; ECOG PS 0/1: 7/32; adeno/squamous/large cell carcinoma: 20/13/6; stage IIIA 19 p and stage IIIB 20 p. All p were evaluable for response and toxicity. RR: 3 CR, 27 PR (RR 77%; 95% CI: 64-90), 5 SD (12.8%) and 4 PD (10.2%). The median PFS was 12 months (95% CI: 7-17) and median OS was 36 months (95% CI: 14-58). The PFS at 1/3 years were 46%/22% and the OS at 1/3 years were 75%/47%. Main toxicities (NCI-CTC 4.0) per p in CChRT (109 cycles of chemotherapy, 2.9 per p; mean doses RT: 65,3 Gys) grade 1-2/3-4 (%) were: neutropenia 32.4/25.6; anemia 32.4/10.8; thrombocytopenia 13.5/2.7; nausea/vomiting 27/2.7; fatigue 28.2/0; esophagitis 43.5/5.4 and pneumonitis 17.9/0; hospitalizations were necesary in 13 p: the most important were febrile neutropenia (6 p) and grade 3 esophagitis (2 p). Conclusions: CChRT with Cisplatin and intravenous and oral Vinorelbine during thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage III NSCLC, showing good clinical efficacy and tolerability with excellent long-term survival.
Background: A combined concurrent therapy with a platinum-based regimen and radiation is recognized as a standard for patients with unresectable stage III lung cancer. Though combined therapy has improved survival, little improvement was reported after that for decades. Pemetrexed is a new generation drug which is widely recognized as a safe and effective agent for patients with stage IV lung cancer. Moreover pemetrexed is expected to have a synergistic effect with radiation in vitro study. The purpose of this study was to investigate safety and toxicity profile of a regimen of pemetrexed/ carboplatin (Pem/CBDCA) plus concurrent thoracic radiotherapy (TRT) followed by consolidation therapy with Pem/CBDCA for Japanese patients with unresectable non-small cell lung cancer (NSCLC). Methods: We planned a multi-institutional open clinical phase I/II trial of Pem (500 mg/m 2 ) /CBDCA (AUC¼5) plus concurrent TRT for patients with stage IIIA/IIIB NSCLC. Patients were administered two cycles of Pem/ CBDCA with three-weeks interval and delivered 60 Gy radiotherapy in 30 fractions concurrently. Additional two cycles of Pem/CBDCA with a three-weeks interval were administered after the safety of concurrent therapy was confirmed. Regarding a phase I study, we confirmed a safety of this therapy every three consecutive patients. In case that three or more DLTs in first six patients occurred, a dose of CBDCA was to be decreased from AUC 5 to 4. We planned to enroll thirty patients in this study in total of phaseIandII. Results: Six patients were included in the phase I study. Median follow-up period was 27.4 month. DLTs were observed in two out of six patients. This fulfilled preplanned criterion to conclude therapeutic dose. The most frequent non-hematologic adverse event was esophagitis (66.7%). Neutropenia was observed rather frequently (83.3%), but no patients developed febrile neutropenia. As to two cases of DLT, one patient experienced grade 2 radiation pneumonitis. The other patient presented prolonged leukocytopenia. Other four patients completed scheduled therapy. Five patients (83.3%) got PR. Two-year survival was 100%. Disease progression was observed in three patients during study period. Because of slow accrual, phase II study was not conducted. Conclusion: Present therapy is feasible for Japanese patients with unresectable stage III NSCLC. Trial registration: UMIN000008426.
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