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.
Keywords
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Article info
Publication history
Received:
May 19,
2009
Identification
Copyright
© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
