Fiche publication
Date publication
novembre 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAIGNEAU Loïc
,
Pr PIVOT Xavier
,
Dr ROYER Bernard
,
Dr THIERY-VUILLEMIN Antoine
,
Dr DEMARCHI Martin
Tous les auteurs :
Thiery-Vuillemin A, Dobi E, Nguyen T, Royer B, Montange D, Maurina T, Kalbacher E, Bazan F, Villanueva C, Demarchi M, Chaigneau L, Ivanaj A, Pivot X
Lien Pubmed
Résumé
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 (3x25 mg/day) for 10 days in combination with carboplatin AUC 5 presents acceptable toxicity and efficacy. The main toxicity remains hematological.
Référence
Anticancer Drugs. 2010 Nov;21(10):958-62.
