Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer

Invest New Drugs. 2013 Feb;31(1):175-82. doi: 10.1007/s10637-012-9842-6. Epub 2012 Jul 3.

Abstract

Introduction: This multicenter, open-label, phase II study was carried out to compare the efficacy and safety of cilengitide (EMD 121974), a selective inhibitor of the cell-surface integrins αVβ3 and αVβ5, with that of docetaxel in patients with advanced non-small-cell lung cancer (NSCLC).

Methods: Patients (n = 140) with advanced NSCLC who had failed first-line chemotherapy were randomized to cilengitide 240, 400, or 600 mg/m(2) twice weekly, or docetaxel 75 mg/m(2) once every 3 weeks for eight cycles. Non-progressing patients could continue cilengitide for up to 1 year. The primary endpoint was progression-free survival (PFS). No statistical tests were performed since the study was exploratory in nature and the number of patients enrolled was relatively small.

Results: Median PFS was 54, 63, 63, and 67 days for cilengitide 240, 400, and 600 mg/m(2), and docetaxel 75 mg/m(2), respectively. One-year survival rates were 13 %, 13 %, 29 %, and 27 %, respectively. The response rate (partial response only) with docetaxel was 15 %. No responses were reported in any cilengitide arm. The most frequent grade 3/4 treatment-related adverse events in the docetaxel group were leukopenia and neutropenia (experienced by 13 % of patients). Hematologic toxicity of this severity did not occur in cilengitide-treated patients.

Conclusion: With the highest dose of cilengitide (600 mg/m(2)), median PFS and 1-year survival were similar to those in patients treated with docetaxel 75 mg/m(2) and there were fewer grade 3/4 treatment-related adverse events.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease-Free Survival
  • Docetaxel
  • Female
  • Humans
  • Integrins / antagonists & inhibitors*
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Snake Venoms / administration & dosage*
  • Snake Venoms / adverse effects
  • Taxoids / administration & dosage
  • Taxoids / adverse effects

Substances

  • Antineoplastic Agents
  • Integrins
  • Snake Venoms
  • Taxoids
  • Docetaxel
  • Cilengitide