TY - JOUR
T1 - Phase I dose escalation study of pegylated liposomal doxorubicin (Caelyx®) in combination with topotecan in patients with advanced malignancies
AU - Ghesquières, Hervé
AU - Faivre, Sandrine
AU - Djafari, Latifa
AU - Pautier, Patricia
AU - Lhomnié, Catherine
AU - Lozahic, Stéphanie
AU - Djazouli, Kamel
AU - Armand, Jean Pierre
AU - Raymond, Eric
PY - 2006/9/1
Y1 - 2006/9/1
N2 - 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/dl 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.
AB - 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/dl 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.
KW - Ovarian cancer
KW - Topoisomerase I inhibitors
KW - Topoisomerase II inhibitors
UR - http://www.scopus.com/inward/record.url?scp=33745045185&partnerID=8YFLogxK
U2 - 10.1007/s10637-006-7520-2
DO - 10.1007/s10637-006-7520-2
M3 - Article
C2 - 16763786
AN - SCOPUS:33745045185
SN - 0167-6997
VL - 24
SP - 413
EP - 421
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 5
ER -