A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma.

BACKGROUND Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. METHODS Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). RESULTS With a median follow-up time of 12.2 months (27–65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). CONCLUSIONS Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases. Cancer 1999;85:2562–9. © 1999 American Cancer Society.