Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer.

Abstract

BACKGROUND/PURPOSE:

This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinum-sensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC).

METHODS:

Patients with recurrent platinum-sensitive EOC with no more than 2 prior courses of chemotherapy were randomized to single-agent sorafenib 400 mg twice daily or combination sorafenib 400 mg bid (days 2-19) with IV carboplatin (AUC 6) and IV paclitaxel 175 mg/m(2) (S+C/T) every 3 weeks. Single agent sorafenib could cross over to combination upon progression.

RESULTS:

Patients were initially randomized to either arm, however, due to poor accrual, sorafenib arm was prematurely closed. A total of 13 patients were evaluable for response to sorafenib and 23 patients were evaluable for response to S+C/T. Objective response rate (RR) was 15 % for patients on sorafenib vs. 61 % for patients on S+C/T (p = 0.014); stable disease was seen in 62 % and 35 %, respectively. Clinical benefit rate (CBR) at 4 months (mos.) was 69 % for S and 65 % for S+C/T. The median progression free survival was 5.6 months on sorafenib vs. 16.8 months on S+C/T (p = 0.012) and there was no significant difference of overall survival between two arms (p = 0.974) with median overall survival 25.6 months under sorafenib vs. 25.9 months on S+C/T. Patients remained on trial for a median of 7.8 cycles on sorafenib and 5.4 cycles on S+C/T.

CONCLUSION:

Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinum-sensitive EOC. Sorafenib in combination with carboplatin and paclitaxel improved RR and PFS; however, there were increased grade and frequencies of toxicities.

• Authors: Anita Schwandt, Vivian E von Gruenigen, Robert M Wenham, Heidi Frasure, Susan Eaton, Nancy Fusco, Pingfu Fu, John J Wright, Afshin Dowlati, Steven Waggoner
• Journal: Investigational new drugs (Invest New Drugs) Vol. 32 Issue 4 Pg. 729-38 (Aug 2014) ISSN: 1573-0646 [Electronic] United States
• PMID: 24619298 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Phenylurea Compounds
• Niacinamide
• Sorafenib
• Carboplatin
• Paclitaxel

Topics

• Aged
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Ovarian Epithelial
• Disease-Free Survival
• Drug Administration Schedule
• Fallopian Tube Neoplasms (drug therapy)
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Neoplasms, Glandular and Epithelial (drug therapy)
• Niacinamide (administration & dosage, analogs & derivatives)
• Organoplatinum Compounds (therapeutic use)
• Ovarian Neoplasms (drug therapy)
• Paclitaxel (administration & dosage)
• Peritoneal Neoplasms (drug therapy)
• Phenylurea Compounds (administration & dosage)
• Sorafenib