Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma

J Natl Cancer Inst. 2003 Apr 16;95(8):605-10. doi: 10.1093/jnci/95.8.605.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Confidence Intervals
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Leucine / administration & dosage
  • Leucine / adverse effects
  • Leucine / analogs & derivatives*
  • Leucine / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Prospective Studies
  • Protease Inhibitors / therapeutic use
  • Survival Analysis
  • Time Factors
  • Treatment Failure
  • Treatment Outcome


  • Antibiotics, Antineoplastic
  • Protease Inhibitors
  • Leucine
  • ubenimex