Japanese Journal of Clinical Oncology 31:488-494 (2001)
© 2001 Foundation for Promotion of Cancer Research
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)
1Division of Internal Medicine, National Nishigunma Hospital, Shibukawa, Gunma, 2Department of Internal Medicine, National Cancer Center Hospital, Tokyo, 3Department of Internal Medicine, Aichi Cancer Center, Nagoya, 4Department of Therapeutic Radiology, Aichi Cancer Center, Nagoya, 5Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Maebashi, Gunma, 6Department of Thoracic Diseases, Tochigi Cancer Center, Utsunomiya, 7Internal Medicine III, National Defense Medical College, Tokorozawa, Saitama, 8Department of Respiratory Medicine, Toranomon Hospital, Tokyo, 9Division of Respiratory Medicine, Gifu Municipal Hospital, Gifu, 10Department of Internal Medicine, Nagano Municipal Hospital, Nagano, 11Division of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, 12Department of Respiratory Medicine, Nagoya National Hospital, Nagoya, 13First Department of Internal Medicine, University of the Ryukyus, Okinawa and 14Cancer Information and Epidemiology Division, National Cancer Center Research Institute, Tokyo, Japan
Background: We attempted dose escalation of standard-fractionated and accelerated-hyperfractionated radiotherapy combined with concurrent cisplatin and 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 1997. There were 19 males and two females and their median age was 65 years (range 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-hyperfractionated radiotherapy arm (n = 11) with two or three cycles of concomitant cisplatin 80 mg/m2 on day 1 and vindesine 3 mg/m2 on days 1 and 8 every 4 weeks in both arms. Dose escalation from 60 Gy/30 fractions/6 weeks to 70 Gy/35 fractions/7 weeks was planned in the standard-fractionated radiotherapy 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-hyperfractionated 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-hematological toxicity consisted of esophagitis 0/3, increased serum total bilirubin 2/0 and hypoxia 0/1. Two patients died of radiation pneumonitis in the standard-fractionated radiotherapy group. Dose-limiting toxicity was observed 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 accelerated-hyperfractionated radiotherapy, 54 Gy/36 fractions/3.6 weeks, respectively. Thus, we failed to escalate the dose of radiotherapy in both arms. The overall response rate in the standard-fractionated group and the accelerated-hyperfractionated radiotherapy group was 70 and 73% and the 1-year survival rate was 70 and 64%, respectively.
Conclusions: We concluded that these schedules of radiotherapy with concurrent cisplatin and vindesine were unacceptable for use in patients with unresectable non-small cell lung cancer. Further modifications of the schedule for radiotherapy and evaluation of combination with new chemotherapy are warranted.
+ For reprints and all correspondence: Yuichiro Ohe, Department of Internal Medicine, National Cancer Center Hospital, 1–1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: yohe@ncc.go.jp
Abbreviations: JCOG, Japan Clinical Oncology Group; NSCLC, non-small cell lung cancer; CALGB, Cancer and Leukemia Group B; NCCTG, North Central Cancer Treatment Group; SDF, standard-fractionated; AHF, accelerated-hyperfractionated; RTOG, Radiation Therapy Oncology Group; ECOG, Eastern Cooperative Oncology Group; PS, performance status; PaO2, partial pressure of arterial oxygen; DLCO, % carbon monoxide diffusing capacity of the lung; CT, computed tomography; EORTC, European Organization for Research and Treatment of Cancer; DLT, dose-limiting toxicity, MTD, maximum tolerated dose