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.

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.

• Authors: Christian Manegold, Johan Vansteenkiste, Felipe Cardenal, Wolfgang Schuette, Penella J Woll, Ernst Ulsperger, Anne Kerber, Josef Eckmayr, Joachim von Pawel
• Journal: Investigational new drugs (Invest New Drugs) Vol. 31 Issue 1 Pg. 175-82 (Feb 2013) ISSN: 1573-0646 [Electronic] United States
• PMID: 22752690 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, 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, adverse effects)
• Taxoids (administration & dosage, adverse effects)