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 t he treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCL C given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy fol lowed by accelerated thoracic radiotherapy. METHODS. Forty-two patients with Stage IIIA and IIIB NSCLC were entered int o the study. Treatment consisted of cisplatin 100 mg/m(2) given on Days 1 a nd 29 and vinorelbine 30 mg/m(2) given weekly for 5 weeks, with a planned 5 0% dose reduction Forty-two patients with Stage IIIA and IIIB NSCLC were en tered into the to 15 mg/m(2) planned for Week 2. This was followed by thora cic 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 surv ivors), 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% a fter radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemothe rapy (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 toxi city was nausea (21.4%). CONCLUSIONS. Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably wit h those reported for other regimens of chemotherapy and standard fractionat ed radiotherapy. The data from this study suggest that the responses of pat ients with clinically apparent disease to induction chemotherapy might indi cate a likelihood of controlling microscopic distant metastases. Cancer 199 9;85:2562-9. (C) 1999 American Cancer Society.