A phase I study of paclitaxel and altretamine as second-line therapy to cisplatin regimens for ovarian cancer

Autor: Andrew G. Ellis, Ian N. Olver, So-Hyang Park, Lorraine K. Webster, Merrill J. Egorin, Margaret Davy, Diana Lüftner
Rok vydání: 2001
Předmět:
Zdroj: Cancer Chemotherapy and Pharmacology. 48:109-114
ISSN: 1432-0843
0344-5704
Popis: Purpose: The efficacy and pharmacokinetics of paclitaxel when combined with altretamine for ovarian cancer were studied. Methods: A group of 30 patients, whose only chemotherapy was one or more cisplatin-based non-paclitaxel-containing regimens and whose ovarian cancer failed to respond or had relapsed within 6 months of their last platinum regimen, received paclitaxel as a 3-h intravenous infusion and altretamine given orally in four divided doses daily for 14 days repeated every 28 days. Doses were escalated from paclitaxel/altretamine 135/150 mg/m2 to 250/300 mg/m2 in cohorts of three patients. Results: The dose-limiting toxicities at 250/300 mg/m2 were WHO grade 3 myalgias and arthralgias in two patients and grade 3 lethargy, stomach cramps, peripheral neuropathy and vomiting in single patients. Considering all dose levels in cycle 1, 16 patients had grade 3 or 4 neutropenia but there was only one episode of febrile neutropenia. Other grade 3 toxicities were vomiting in four patients, myalgias in three, peripheral neuropathy in two and lethargy in two. Grade 3 alopecia occurred in 23 patients. Three patients achieved a complete response and 12 achieved a partial response for an overall objective response rate of 50%. Responses occurred at all dose levels of 175/150 mg/m2 and higher. The median freedom from progression was 35 weeks, with a median survival of 55 weeks. Altretamine did not alter the pharmacokinetics of paclitaxel and there were no consistent differences in paclitaxel pharmacokinetic parameters or toxicities between course 1 and 2. No dose-response relationships were evident above paclitaxel/altretamine 175/150 mg/m2. Conclusion: Paclitaxel and altretamine can be safely combined and with a high response rate in relapsed ovarian cancer, justifying further studies with this combination.
Databáze: OpenAIRE
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