Randomized phase I study of standard-fractionated or accelerated-hyperfractionated radiotherapy with concurrent cisplatin and vindesine for unresectable non-small cell lung cancer: a report of Japan Clinical Oncology Group Study (JCOG 9601)

Background: We attempted dose escalation of standard-fractionated and accel erated-hyperfractionated radiotherapy combined with concurrent cisplatin an d vindesine to improve local control and survival in unresectable non-small cell lung cancer. Methods: Twenty-one patients were enrolled between June 1996 and August 199 7. There were 19 males and two females and their median age was 65 years (r ange 45-74 years). Performance status was 0 in 10 cases and 1 in 11 cases. Disease stage was IIIA in three cases and IIIB in 18 cases. The cases were randomized to a standard-fractionated arm (n = 10) or an accelerated-hyperf ractionated radiotherapy arm (n = 11) with two or three cycles of concomita nt cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8 ev ery 4 weeks in both arms. Dose escalation from 60 Gy/30 fractions/6 weeks t o 70 Gy/35 fractions/7 weeks was planned in the standard-fractionated radio therapy group and from 54 Gy/36 fractions/3.6 weeks to 60 Gy/40 fractions/4 weeks and then 66 Gy/44 fractions/4.4 weeks in the accelerated-hyperfracti onated radiotherapy group. Results: Grade 3 or 4 hematological toxicities were observed as follows: in the standard-fractionated/accelerated-hyperfractionated radiotherapy group , leukocytopenia 9/10, anemia 2/3 and thrombocytopenia 0/2. Grade 3 non-hem atological toxicity consisted of esophagitis 0/3, increased serum total bil irubin 2/0 and hypoxia 0/1. Two patients died of radiation pneumonitis in t he standard-fractionated radiotherapy group. Dose-limiting toxicity was obs erved in four of the 10 and seven of the 11 patients at initial dose level of standard-fractionated radiotherapy, 60 Gy/30 fractions/6 weeks, and of a ccelerated-hyperfractionated radiotherapy, 54 Gy/36 fractions/3.6 weeks, re spectively. Thus, we failed to escalate the dose of radiotherapy in both ar ms. The overall response rate in the standard-fractionated group and the ac celerated-hyperfractionated radiotherapy group was 70 and 73% and the 1-yea r survival rate was 70 and 64%, respectively. Conclusions: We concluded that these schedules of radiotherapy with concurr ent cisplatin and vindesine were unacceptable for use in patients with unre sectable non-small cell lung cancer. Further modifications of the schedule for radiotherapy and evaluation of combination with new chemotherapy are wa rranted.