Phase II trial of bevacizumab with dose-dense paclitaxel as first-line treatment in patients with advanced ovarian cancer.

Abstract

OBJECTIVES:

To assess the tolerability and efficacy of bevacizumab with carboplatin and weekly paclitaxel as first-line adjuvant therapy for advanced stage ovarian cancer.

METHODS:

After IRB approval, this single-institution, phase II study enrolled patients with stage III or IV epithelial ovarian cancer after primary cytoreductive surgery to treatment with carboplatin (AUC 5), weekly paclitaxel (80mg/m2), and bevacizumab (15mg/kg) every 3weeks for at least 6cycles. The primary endpoint was tolerability of at least 4cycles of therapy, with a target treatment success rate of >60%. Secondary endpoints included progression-free survival (PFS) and response rate. Plasma biomarkers were analyzed by the multiplex ELISA assays.

RESULTS:

Thirty-three patients were enrolled with 30 evaluable patients receiving at least one cycle of combination treatment. Twenty-three patients (77%) were able to complete at least 4cycles of therapy per protocol, and the posterior probability that the treatment success rate is >60% is 0.77. Twenty-one patients (70%) were able to complete ≥6cycles of therapy. Median PFS was 22.4months for patients with optimal (R0) compared to 16.9months for optimal≤1cm (HR 1.71, 95% CI 0.58-4.98, p=0.33), and 16.9months for suboptimal>1cm (HR 3.75, 95% CI 1.05-13.34, p=0.04) disease. Increases in mean Flt-3L was significantly higher in responders versus non-responders (83.4 vs. 28pg/mL, p=0.05).

CONCLUSIONS:

Adjuvant bevacizumab with dose-dense chemotherapy is associated with acceptable toxicity and a high likelihood of completing 4cycles of therapy. Dynamic changes in Flt-3L may represent a predictive marker to treatment response.

• Authors: Nicole D Fleming, Robert L Coleman, Celestine Tung, Shannon N Westin, Wei Hu, Yunjie Sun, Priya Bhosale, Mark F Munsell, Anil K Sood
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 147 Issue 1 Pg. 41-46 (10 2017) ISSN: 1095-6859 [Electronic] United States
• PMID: 28774461 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Biomarkers, Tumor
• Cytokines
• Bevacizumab
• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab (administration & dosage)
• Biomarkers, Tumor (blood)
• Carboplatin (administration & dosage)
• Cytokines (blood)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Humans
• Middle Aged
• Non-Randomized Controlled Trials as Topic
• Ovarian Neoplasms (blood, drug therapy, mortality)
• Paclitaxel (administration & dosage)
• Predictive Value of Tests