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

详细信息    查看全文

• 作者：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
• 关键词：Bortezomib ; Ovarian cancer ; Proteosome inhibition
• 刊名：Gynecologic Oncology
• 出版年：2009
• 出版时间：November 2009
• 年：2009
• 卷：115
• 期：2
• 页码：215-220
• 全文大小：588 K

文摘

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.