A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: A Gynecologic Oncology Group study

Carol Aghajanian, John A. Blessing, Kathleen M. Darcy, Gary Reid, Koen DeGeest, Stephen C. Rubin, Robert S. Mannel, Jacob Rotmensch, Russell J. Schilder, William Riordan

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Objective: To determine the activity and pharmacodynamics (PD) of bortezomib in platinum-sensitive epithelial ovarian or primary peritoneal cancer (EOC/PPC). Patients and methods: Eligible women with recurrent EOC/PPC progressing between 6 and 12 months after initial chemotherapy were treated with bortezomib on days 1, 4, 8, and 11 [1.5 (cohort I) and 1.3 (cohort II) mg/m2/dose]. Patients must have had initial chemotherapy only. Response Evaluation Criteria in Solid Tumors (RECIST) was assessed by computed tomography (CT) scan every 2 cycles. 20S proteasome activity was quantified in three pre-treatment and a 1-hour post-treatment (cycle one, day 1) whole blood lysates. Results: Initially, 26 evaluable patients were treated at the 1.5 mg/m2/dose level. Objective response rate was 3.8% (1/26), a partial response. An additional 10 patients (38.5%) had stable disease. Given concerns that treatment discontinuations due to toxicity limited drug exposure/activity a second cohort of 29 evaluable patients was accrued at 1.3 mg/m2/dose. The 1.3 mg/m2/dose regimen is currently approved as an indication for multiple myeloma and mantle cell lymphoma. Treatment was more tolerable, although objective responses remained low at 6.9% (2/29, partial responses). Second stage accrual was not warranted at either dose. Bortezomib effectively inhibited 20S proteasome activity in whole blood lysates between 37 and 92% in 24/25 (96%) patients in cohort I, and 14-84% in 27/28 (96%) patients in cohort II who provided satisfactory pre- and post-treatment specimens for testing. Conclusion: Bortezomib has minimal activity as a single-agent in the treatment of recurrent platinum-sensitive EOC/PPC. Treatment with bortezomib at 1.5 mg/m2/dose was not feasible in this patient population due to excess toxicity. Bortezomib was well tolerated at 1.3 mg/m2/dose.

Original languageEnglish (US)
Pages (from-to)215-220
Number of pages6
JournalGynecologic oncology
Volume115
Issue number2
DOIs
StatePublished - Nov 1 2009

Keywords

  • Bortezomib
  • Ovarian cancer
  • Proteosome inhibition

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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    Aghajanian, C., Blessing, J. A., Darcy, K. M., Reid, G., DeGeest, K., Rubin, S. C., Mannel, R. S., Rotmensch, J., Schilder, R. J., & Riordan, W. (2009). A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: A Gynecologic Oncology Group study. Gynecologic oncology, 115(2), 215-220. https://doi.org/10.1016/j.ygyno.2009.07.023