© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 8, 605-610,
April 16, 2003
© 2003 Oxford University Press
ARTICLE |
Randomized Double-Blind Placebo-Controlled Trial of Bestatin in Patients With Resected Stage I Squamous-Cell Lung Carcinoma
For the NK421 Lung Cancer Surgery Group
Affiliations of authors: Y. Ichinose, M. Ohta, Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan; K. Genka, Department of Surgery, National Okinawa Hospital, Okinawa, Japan; T. Koike, Division of Chest Surgery, Niigata Cancer Center Hospital, Niigata, Japan; H. Kato, Department of Surgery, Tokyo Medical University, Tokyo, Japan; Y. Watanabe, Department of Surgery, Kanazawa University, School of Medicine, Kanazawa, Japan; T. Mori, Department of Thoracic Surgery, National Kinki-Chuo Hospital for Chest Disease, Osaka, Japan; S. Iioka, Department of General Thoracic Surgery, Osaka City General Hospital, Osaka; A. Sakuma, Department of Clinical Pharmacology, Tokyo Medical and Dental University, Tokyo.
Correspondence to: Yukito Ichinose, M.D., Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka 811–1395, Japan (e-mail: yichinos{at}nk-cc.go.jp).
Background: Bestatin is a potent aminopeptidase inhibitor that has immunostimulant and antitumor activity. We conducted a prospective randomized, double-blind, placebo-controlled trial to determine whether postoperative adjuvant treatment with bestatin could prolong the survival of patients with completely resected stage I squamous-cell lung carcinoma. Methods: Patients with confirmed, resected stage I squamous-cell lung carcinoma were randomly assigned to receive either bestatin (30 mg) or placebo daily by mouth for 2 years. We assessed whether bestatin treatment was associated with overall survival and 5-year cancer-free survival and assessed its safety. All statistical tests were two-sided. Results: From July 8, 1992, through March 30, 1995, 402 patients were entered in the study, 202 in the bestatin group and 198 in the placebo group. The median follow-up for surviving patients was 76 months (range = 58–92 months). The 5-year overall survival was 81% in the bestatin group and 74% in the placebo group for a difference of 7% (95% confidence interval [CI] = -1.4% to 15.0%). The 5-year cancer-free survival was 71% in the bestatin group and 62% in the placebo group for a difference of 9% (95% CI = -0.7% to 17.8%). Overall survival (P = .033, log-rank test) and cancer-free survival (P = .017, log-rank test) were statistically significantly different by Kaplan–Meier analysis. Few adverse events were observed in either group. Conclusions: Survival was statistically significantly better for patients with completely resected stage I squamous-cell lung carcinoma who were treated with bestatin as a postoperative adjuvant therapy than for those who received a placebo. This result requires confirmation in other phase III trials.
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