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/m(2)/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/m(2)/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/m(2)/dose. The 1.3 mg/m(2)/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/m(2)/dose was not feasible in this patient population due to excess toxicity. 
Bortezomib was well tolerated at 1.3 mg/m(2)/dose.