Phase I trial of bortezomib and carboplatin in recurrent ovarian or primary peritoneal cancer Journal Article
| Authors: | Aghajanian, C.; Dizon, D. S.; Sabbatini, P.; Raizer, J. J.; Dupont, J.; Spriggs, D. R. |
| Article Title: | Phase I trial of bortezomib and carboplatin in recurrent ovarian or primary peritoneal cancer |
| Abstract: | Purpose: To determine the maximum-tolerated dose, pharmacodynamics, and safety of the combination of bortezomib and carboplatin in recurrent ovarian cancer. Patients and Methods: Fifteen patients were treated with a fixed dose of carboplatin (area under the curve [AUC] 5) and increasing doses of bortezomib (0.75, 1, 1.3, and 1.5 mg/m2/dose). Patients must have received upfront chemotherapy and up to two prior chemotherapy regimens for recurrent disease. Neurologic evaluation was performed at baseline and after every two cycles by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group neurotoxicity questionnaire and examination by an attending neurologist. All patients received carboplatin alone in cycle 1 to establish baseline pharmacodynamics for nuclear factor-kappa B (NF-kB). Starting with cycle 2, patients were treated with carboplatin on day 1 and bortezomib on days 1,4, 8, and 11. Results: Diarrhea, rash, neuropathy, and constipation (with colonic wall thickening on computed tomography) were dose-limiting toxicities, occurring in the two patients treated at the 1.5 mg/m2/dose level. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group neurotoxicity questionnaire was helpful in guiding the need for dose reductions. Neurotoxicity was manageable through six cycles, with appropriate dose reductions. Carboplatin had no effect on bortezomib pharmacodynamics as measured by percent inhibition of the 20S proteasome. Bortezomib decreased carboplatin-induced NF-kB. The overall response rate to this combination was 47%, with two complete responses (CR) and five partial responses, including one CR in a patient with platinum-resistant disease. Conclusion: The recommended phase II dose of bortezomib administered in combination with carboplatin (AUC 5) is 1.3 mg/m 2/dose. © 2005 by American Society of Clinical Oncology. |
| Keywords: | adult; clinical article; controlled study; treatment outcome; aged; middle aged; clinical trial; constipation; area under the curve; diarrhea; drug dose reduction; drug potentiation; drug safety; drug withdrawal; monotherapy; nonhuman; recommended drug dose; recurrent cancer; antineoplastic agent; anorexia; ovarian neoplasms; drug inhibition; carboplatin; bortezomib; controlled clinical trial; enzyme inhibition; multiple cycle treatment; ovary cancer; peritoneum cancer; boronic acids; neoplasm recurrence, local; peritoneal neoplasms; pyrazines; neuropathy; antineoplastic combined chemotherapy protocols; dehydration; animal experiment; animal model; combination chemotherapy; immunoglobulin enhancer binding protein; pathology; asthenia; drug dose escalation; rash; tumor recurrence; ovary tumor; drug response; single drug dose; maximum tolerated dose; phase 1 clinical trial; infusions, intravenous; boronic acid derivative; pyrazine derivative; hypersensitivity reaction; peritoneum tumor; intravenous drug administration; injections, intravenous; orthostatic dehydration |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 23 |
| Issue: | 25 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2005-09-01 |
| Start Page: | 5943 |
| End Page: | 5949 |
| Language: | English |
| DOI: | 10.1200/jco.2005.16.006 |
| PUBMED: | 16135465 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 70" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus" |
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325Spriggs
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