title: Phase I dose escalation study of pegylated liposomal doxorubicin (Caelyx) in combination with topotecan in patients with advanced malignancies.
abstract: Aims of this study were to determine the toxicity profile and the recommended dose of pegylated liposomal doxorubicin (Caelyx) in combination with topotecan in patients with advanced malignancies. Caelyx: 35 (DLI) or 40 (DLII) mg/m2/d1 was followed by 0.5 mg/m2/d topotecan daily for 5 days, every 4 weeks. Twenty-three patients received a total of 82 cycles. At DLII, 2/6 patients experienced dose-limiting toxicity consisting of grade 4 neutropenia lasting for more than 7 days and febrile neutropenia. At DLI, 4/18 and 2/18 patients presented febrile neutropenia and grade 4 sustained neutropenia, respectively. Non-hematological toxicities were mild to moderate. One patient with ovarian cancer presented a complete response. The hematological toxicity was a dose limiting factor that led to the recommended dose of 35 mg/m2 Caelyx on day 1 with 0.5 mg/m2/d topotecan on days 1-5. This study results suggest that alternative schedules of this combination are required.
authors.affiliation: Department of Medicine, Institut Gustave-Roussy, Villejuif.
authors.forename: Hervé
authors.initials: H
authors.lastname: Ghesquières
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: Latifa
authors.initials: L
authors.lastname: Djafari
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.forename: Catherine
authors.initials: C
authors.lastname: Lhommé
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lozahic
authors.forename: Kamel
authors.initials: K
authors.lastname: Djazouli
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Armand
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D004317:Doxorubicin