Phase I study of pegylated liposomal doxorubicin (Caelyx) in combination with carboplatin in patients with advanced solid tumors.
OBJECTIVE
To determine the maximum tolerated dose of the combination of Carboplatin and Caelyx, a pegylated liposomal doxorubicin, with promising activities in various solid tumors.


METHODS
Twenty-two patients with various advanced solid tumors were included. Three dose levels of Caelyx were explored: 30, 35 and 40 mg/m2 in association with a fixed dose of Carboplatin (AUC 5) every 3 weeks. Dose escalation followed a modified continuous reassessment method.


RESULTS
Dose-limiting toxicities were almost exclusively hematological: 3 febrile neutropenia, 1 grade 4 neutropenia lasting more than 7 days and 2 grade 4 thrombopenia were observed. Grade 4 neutropenia and febrile neutropenia were observed in 20 and 10% of courses, respectively. The median interval between courses was 25 days after cycle 1 and 27-28 days after subsequent cycles. Palmar-plantar erythrodysesthesia, mucositis and other non hematological toxicities were mild and uncommon. One patient experienced a severe anaphylactic reaction immediately after Caelyx infusion. No clinical heart dysfunction was observed. Three patients responded to therapy including 2 clinical complete responses in relapsing ovarian cancer.


CONCLUSIONS
The recommended dose for future studies is Caelyx 35 mg/m2 + Carboplatin AUC 5 every 3 or 4 weeks. Antitumor activity, especially in ovarian cancer, warrants further investigation in phase II studies.
Gonçalves
A
A
Institut Paoli-Calmettes-Department of Medical Oncology, 232 Boulevard Sainte Marguerite, 13273 Marseille, France. oncomed@marseille.fnclcc.fr
Braud
A C
AC
Viret
F
F
Genre
D
D
Gravis
G
G
Tarpin
C
C
Giovannini
M
M
Maraninchi
D
D
Viens
P
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D008081:Liposomes; D004317:Doxorubicin; D016190:Carboplatin