Phase I dose escalation study of pegylated liposomal doxorubicin (Caelyx) in combination with topotecan in patients with advanced malignancies.
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.
Ghesquières
Hervé
H
Department of Medicine, Institut Gustave-Roussy, Villejuif.
Faivre
Sandrine
S
Djafari
Latifa
L
Pautier
Patricia
P
Lhommé
Catherine
C
Lozahic
Stéphanie
S
Djazouli
Kamel
K
Armand
Jean-Pierre
JP
Raymond
Eric
E
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
D000970:Antineoplastic Agents; D019772:Topotecan; D004317:Doxorubicin