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, Koenraad De Geest, Stephen C. Rubin, Robert S. Mannel, Jacob Rotmensch, Russell J. Schilder, William Riordan

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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 2009
Externally publishedYes

Fingerprint

Platinum
Neoplasms
Proteasome Endopeptidase Complex
Therapeutics
Mantle-Cell Lymphoma
Drug Therapy
Bortezomib
Drug-Related Side Effects and Adverse Reactions
Multiple Myeloma
Tomography
Population

Keywords

  • Bortezomib
  • Ovarian cancer
  • Proteosome inhibition

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer : A Gynecologic Oncology Group study. / Aghajanian, Carol; Blessing, John A.; Darcy, Kathleen M.; Reid, Gary; De Geest, Koenraad; Rubin, Stephen C.; Mannel, Robert S.; Rotmensch, Jacob; Schilder, Russell J.; Riordan, William.

In: Gynecologic Oncology, Vol. 115, No. 2, 11.2009, p. 215-220.

Research output: Contribution to journalArticle

Aghajanian, Carol ; Blessing, John A. ; Darcy, Kathleen M. ; Reid, Gary ; De Geest, Koenraad ; Rubin, Stephen C. ; Mannel, Robert S. ; Rotmensch, Jacob ; Schilder, Russell J. ; Riordan, William. / A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer : A Gynecologic Oncology Group study. In: Gynecologic Oncology. 2009 ; Vol. 115, No. 2. pp. 215-220.
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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.",
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author = "Carol Aghajanian and Blessing, {John A.} and Darcy, {Kathleen M.} and Gary Reid and {De Geest}, Koenraad and Rubin, {Stephen C.} and Mannel, {Robert S.} and Jacob Rotmensch and Schilder, {Russell J.} and William Riordan",
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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 - De Geest, Koenraad

AU - Rubin, Stephen C.

AU - Mannel, Robert S.

AU - Rotmensch, Jacob

AU - Schilder, Russell J.

AU - Riordan, William

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.

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KW - Ovarian cancer

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