Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV.

Abstract

OBJECTIVES:

This study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).

PATIENTS AND METHODS:

We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175 mg/m(2)) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.

RESULTS:

105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm: median PFS was 11.5 months (95% CI: 7.4-14.2) compared with 16.4 (95% CI: 10.3-40.4) for TC (p=0.0141; HR=0.36 (95% CI: 0.15-0.84)) with median OS 20.6 months (95% CI: 13.1-31.0) and 43.4 months (95% CI: 15.7-) for the TC arm (p=0.012; HR=0.32 (95% CI: 0.13-0.8)).

CONCLUSION:

The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.

• Authors: Werner Meier, Andreas du Bois, Jörn Rau, Martina Gropp-Meier, Klaus Baumann, Jens Huober, Kerstin Wollschlaeger, Rolf Kreienberg, Ulrich Canzler, Barbara Schmalfeldt, Pauline Wimberger, Barbara Richter, Willibald Schröder, Antje Belau, Anne Stähle, Alexander Burges, Jalid Sehouli
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 126 Issue 2 Pg. 236-40 (Aug 2012) ISSN: 1095-6859 [Electronic] United States
• PMID: 22564713 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Piperidines
• Pyridines
• Carboplatin
• lonafarnib
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Carcinoma, Ovarian Epithelial
• Disease-Free Survival
• Female
• Humans
• Middle Aged
• Neoplasm Staging
• Neoplasms, Glandular and Epithelial (drug therapy, pathology)
• Ovarian Neoplasms (drug therapy, pathology)
• Paclitaxel (administration & dosage, adverse effects)
• Piperidines (administration & dosage, adverse effects)
• Prospective Studies
• Pyridines (administration & dosage, adverse effects)
• Survival Analysis
• Young Adult