Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma.
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.
Ichinose
Yukito
Y
Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan. yichinos@nk-cc.go.jp
Genka
Keiichiro
K
Koike
Teruaki
T
Kato
Harubumi
H
Watanabe
Yoh
Y
Mori
Takashi
T
Iioka
Sogo
S
Sakuma
Akira
A
Ohta
Mitsuo
M
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007930:Leucine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D011480:Protease Inhibitors; D007930:Leucine; C012211:ubenimex