Final report on serial phase II trials of all-intraperitoneal chemotherapy with or without bevacizumab for women with newly diagnosed, optimally cytoreduced carcinoma of Müllerian origin

Gynecol Oncol. 2019 May;153(2):223-229. doi: 10.1016/j.ygyno.2019.02.004. Epub 2019 Feb 12.

Abstract

Background: Intraperitoneal (IP) chemotherapy can improve outcomes for women with optimally cytoreduced epithelial ovarian cancer but toxicities are a concern. We conducted 2 phase 2 trials of an IV/IP regimen using carboplatin and paclitaxel without (Trial A) and with bevacizumab (Trial B).

Methods: Both trials consisted of carboplatin AUC 6 day 1, and paclitaxel 60 mg/m2 on days 1,8, 15 of a 21-day cycle; in Trial B, patients received IV bevacizumab 15 mg/kg every cycle starting cycle 2. Chemotherapy was administered IV for cycle 1 and then IP for all subsequent cycles. Primary objectives included safety and tolerability, pathologic CR rate (Trial A), and the rate of completion of IP cycles of therapy (Trial B). Progression-free (PFS), overall survival (OS), and pharmacokinetic analysis were secondary endpoints.

Results: 81 patients were treated on both trials (n = 40 and 41 in trials A and B, respectively). Median age for trials A and B was 59 (range, 36-76) and 55 (range, 19-69) years, respectively. 68% and 85% of patients, respectively for A and B, completed at least 4 cycles of treatment in both trials. Treatment with bevacizumab resulted in higher rates of grade 3 fatigue (37 versus 33%) and grade 3-4 diarrhea (22 versus 8%). Median PFS was 23.5 (95%CI 16.2-35.3) and 25 (95%CI 16.4-42.7) months, respectively; median OS was 68 (95%CI 49.5-NR) and 79.7 (95%CI 59.0-79.7) months, respectively for Trial A and B.

Conclusions: Weekly administered IP carboplatin and IP paclitaxel is tolerable and safe with similar activity with and without concommittant bevacizumab in these 2 trials.

Keywords: Bevacizumab; Carboplatin; Intraperitoneal chemotherapy; Ovarian cancer; Paclitaxel.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carcinoma, Ovarian Epithelial / mortality
  • Carcinoma, Ovarian Epithelial / pathology
  • Carcinoma, Ovarian Epithelial / therapy*
  • Chemotherapy, Adjuvant / methods
  • Cytoreduction Surgical Procedures / methods
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Infusions, Parenteral
  • Middle Aged
  • Mullerian Ducts / pathology
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Ovariectomy / methods
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Progression-Free Survival
  • Young Adult

Substances

  • Bevacizumab
  • Carboplatin
  • Paclitaxel