TY - JOUR
T1 - A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer
T2 - A Gynecologic Oncology Group study
AU - Aghajanian, Carol
AU - Blessing, John A.
AU - Darcy, Kathleen M.
AU - Reid, Gary
AU - DeGeest, Koen
AU - Rubin, Stephen C.
AU - Mannel, Robert S.
AU - Rotmensch, Jacob
AU - Schilder, Russell J.
AU - Riordan, William
N1 - Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the GOG Tissue Bank (CA 11479) and the GOG Statistical and Data Center (CA 37517), and by Millennium Pharmaceuticals, Inc. (Cambridge, MA). The following GOG member institutions participated in the related treatment study: Duke University Medical Center, Walter Reed Army Medical Center, Colorado Gynecologic Oncology Group, UCCC, University of California at Los Angeles, University of Pennsylvania Cancer Center, University of Cincinnati Medical Center, University of North Carolina, University of Iowa Hospitals and Clinics, Indiana University Cancer Center, Wake Forest University School of Medicine, Tufts-New England Medical Center, Rush University Medical Center, Memorial Sloan-Kettering Cancer Center, Columbus Cancer Council/Ohio State, Fox Chase Cancer Center, University of Oklahoma.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - Bortezomib
KW - Ovarian cancer
KW - Proteosome inhibition
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U2 - 10.1016/j.ygyno.2009.07.023
DO - 10.1016/j.ygyno.2009.07.023
M3 - Article
C2 - 19712963
AN - SCOPUS:70349754173
SN - 0090-8258
VL - 115
SP - 215
EP - 220
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -