Document Detail


Duration: escalation study of oral etoposide with carboplatin in patients with varied solid tumors.
MedLine Citation:
PMID:  20856105     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Prolonged fractionated oral administration of etoposide may present a theoretical advantage over intravenous administration of the bolus. This phase I trial was carried out to determine the recommended duration of oral etoposide in combination with a fixed dose of carboplatin. Nineteen patients with varied solid tumors, who were not candidates for standard chemotherapy, were administered an escalating duration (6, 9 or 12 consecutive days) of oral etoposide (a 25 mg capsule three times daily) combined with carboplatin AUC5 administered on day 1, by a 30  min intravenous infusion, to define the maximum tolerated dose on the basis of the acute toxicities that were reported. Etoposide was started on day 2; the cycles repeated every 28 days until disease progression or toxicity. Pharmacokinetics was carried out during the two first cycles. The maximum tolerated dose was determined to be the 12-day treatment level, with two cases of grade 4 neutropenia, grade 3 anemia and thrombocytopenia. As no severe toxicity occurred with the 9-day treatment level and in an attempt to explore an optimal combination, a new 10-day treatment plan was studied in three patients. As one patient presented dose-limiting toxicity at that level, five additional patients were included to establish the recommended regimen. Nonhematological toxicities among all patients were moderate, consisting of grade 2 nausea and asthenia. No treatment-related death occurred. Objective responses were observed in four patients and stabilization in three patients. Pharmacokinetics highlighted no interaction between etoposide and carboplatin. Fractionated oral etoposide (3×25 mg/day) for 10 days in combination with carboplatin AUC 5 presents acceptable toxicity and efficacy. The main toxicity remains hematological.
Authors:
Antoine Thiery-Vuillemin; Erion Dobi; Thierry Nguyen; Bernard Royer; Damien Montange; Tristan Maurina; Elsa Kalbacher; Fernando Bazan; Cristian Villanueva; Martin Demarchi; Loic Chaigneau; Arben Ivanaj; Xavier Pivot
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  21     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  958-62     Citation Subset:  IM    
Affiliation:
Medical Oncology Unit, CHU Minjoz cINSERM U645 Besancon, France. a.thieryvuillemin@mac.com
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