title: Duration: escalation study of oral etoposide with carboplatin in patients with varied solid tumors.
abstract: 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.affiliation: Medical Oncology Unit, CHU Minjoz cINSERM U645 Besancon, France. a.thieryvuillemin@mac.com
authors.forename: Antoine
authors.initials: A
authors.lastname: Thiery-Vuillemin
authors.forename: Erion
authors.initials: E
authors.lastname: Dobi
authors.forename: Thierry
authors.initials: T
authors.lastname: Nguyen
authors.forename: Bernard
authors.initials: B
authors.lastname: Royer
authors.forename: Damien
authors.initials: D
authors.lastname: Montange
authors.forename: Tristan
authors.initials: T
authors.lastname: Maurina
authors.forename: Elsa
authors.initials: E
authors.lastname: Kalbacher
authors.forename: Fernando
authors.initials: F
authors.lastname: Bazan
authors.forename: Cristian
authors.initials: C
authors.lastname: Villanueva
authors.forename: Martin
authors.initials: M
authors.lastname: Demarchi
authors.forename: Loic
authors.initials: L
authors.lastname: Chaigneau
authors.forename: Arben
authors.initials: A
authors.lastname: Ivanaj
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D016879:Salvage Therapy; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D005047:Etoposide; D016190:Carboplatin