CONCURRENT HYPERFRACTIONATED IRRADIATION AND CHEMOTHERAPY FOR UNRESECTABLE NONSMALL-CELL LUNG-CANCER - RESULTS OF RADIATION-THERAPY ONCOLOGY GROUP-90-15

Background. Clinical trials of hyperfractionated radiation therapy and induction chemotherapy followed by standard radiation therapy have sh own improved survival in patients with unresectable nonsmall cell lung cancer (NSCLC). Radiosensitization may improve local tumor control wh en chemotherapy is given concurrently with hyperfractionated radiation therapy, but also may increase toxicity. A Phase I/II trial, Radiatio n Therapy Oncology Group 90-15, was designed to evaluate whether this strategy could improve survival with acceptable toxicity and be part o f a Phase III trial of chemoradiation sequencing. Methods. Vinblastine (5 mg/M(2) weekly X 5 weeks) and cisplatin (75 mg/M(2) days 1, 29, an d 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart ) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients had America n Joint Committee on Cancer (ATCC) Stage II (unresected) or IIIA-B NSC LC and Karnofsky performance status 70 or greater; there were no weigh t loss restrictions.Results. Of 42 eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary tumors, and 62% were Stage III B. All protocol treatment was completed in 53%. Acute toxicity was pre dominantly hematologic with 19 of 42 (45%) having Grade 4 toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or h igher esophagitis. There were two (4.7%) patients with Grade 3 or high er (1 lung and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 l ung and 1 hematologic) late toxicities. Median survival time was 12.2 months, with an overall 1-year survival of 54%, an estimated 2 year su rvival of 28% and a 1-year progression free survival of 38%. Conclusio ns. For patients with unresectable nonsmall cell lung cancer, who were not selected on the basis of weight loss, concurrent hyperfractionate d irradiation and chemotherapy had more intense acute toxicity than hy perfractionation alone, but late toxicity was acceptable. One and 2-ye ar survival rates were 54 and 28%, respectively.