Abstract | PURPOSE: To compare the safety and efficacy of carboplatin and paclitaxel administered with or without the multidrug resistance modulator valspodar ( PSC 833) in untreated patients with advanced ovarian or primary peritoneal cancer. PATIENTS AND METHODS: Seven hundred sixty-two patients with stage IV or suboptimally debulked stage III ovarian or primary peritoneal cancer were randomly assigned to receive either valspodar 5 mg/kg every 6 hours for 12 doses, paclitaxel 80 mg/m(2), and carboplatin area under the curve (AUC) 6 (PC-PSC; n = 381) or paclitaxel 175 mg/m(2) and carboplatin AUC 6 (PC; n = 381). Time to disease progression ( TTP) was the primary end point. Secondary end points were overall survival time (OS), response rate (RR), safety, and tolerability. RESULTS: With a median follow-up of 736 days (range, 1 to 2,280 days), the median TTP was 13.2 and 13.5 months in the PC-PSC and PC groups, respectively (P = .67); the median OS was 32 and 28.9 months, respectively (P = .94). The overall RR was higher in the PC group (41.5% v 33.6%; P = .02). Central and peripheral nervous system and GI toxicities were more common in the PC-PSC group. Ataxia occurred in 53.5% and 3.2% of PC-PSC-and PC-treated patients, respectively. Febrile neutropenia occurred more frequently in the PC-PSC group. More PC-PSC-treated patients discontinued therapy because of adverse events (AEs), experienced serious AEs, and required paclitaxel dose reductions. CONCLUSION: The addition of valspodar to PC did not improve TTP or OS and was more toxic compared with PC in untreated patients with advanced ovarian or primary peritoneal cancer.
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Authors | Catherine Lhommé, Florence Joly, Joan L Walker, Andrea A Lissoni, Maria O Nicoletto, Gregory M Manikhas, Mark M O Baekelandt, Alan N Gordon, Paula M Fracasso, William L Mietlowski, Gary J Jones, Margaret H Dugan |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 26
Issue 16
Pg. 2674-82
(Jun 01 2008)
ISSN: 1527-7755 [Electronic] United States |
PMID | 18509179
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclosporins
- Carboplatin
- Paclitaxel
- valspodar
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Carboplatin
(administration & dosage, adverse effects)
- Cyclosporins
(administration & dosage, adverse effects, therapeutic use)
- Female
- Humans
- Middle Aged
- Ovarian Neoplasms
(drug therapy, mortality, pathology)
- Paclitaxel
(administration & dosage, adverse effects)
- Peritoneal Neoplasms
(drug therapy, mortality, pathology)
- Survival Analysis
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