Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas.
OBJECTIVE
To assess the objective response rate, toxicity experienced, progression-free survival, and overall survival of patients with previously untreated advanced soft tissue sarcomas treated with a liposomal doxorubicin formulation (Doxil).


METHODS
Patients with metastatic or recurrent soft tissue sarcoma who had received no prior chemotherapy for advanced disease were treated with liposomal doxorubicin (Doxil) according to a two stage accrual design. Doxil was administered at 50 mg/m2 every 4 weeks. A total of 15 patients were treated and are evaluable for response and toxicity.


RESULTS
The male/female ratio was 7/8, the median age was 60 years (34-75) and the ECOG performance status was 0-1 in >90% of patients. Leiomyosarcoma (7/15) and malignant fibrous histiocytoma (2/15) were the most common histologic diagnoses. No objective responses were observed in the 15 evaluable patients. No lethal toxicity occurred. Grade 3-4 leukopenia or neutropenia were reported in 3/15 (20%) patients. Grade 3 mucositis or hand-foot syndrome occurred in 2/15 (13%) and 1/15 (7%) patients respectively and seemed more severe in older patients. The median time to progression was 1.9 months (range 0.9-6.2). Twelve patients have now died. The Kaplan-Meier estimate of median overall survival is 12.3 months. As called for in the study design, accrual was terminated because no responses were obtained in the first 15 patients.


CONCLUSIONS
Though well-tolerated, Doxil given according to this dose and schedule to patients with advanced soft tissue sarcoma had no significant therapeutic activity. A correlation between older age and skin/mucosal toxicity of Doxil is suggested in this study but needs confirmation. Future investigations of Doxil in soft tissue sarcomas should use a different schedule and dose.
Chidiac
T
T
The Taussig Cancer Center, Cleveland Clinic Foundation, OH 44195, USA.
Budd
G T
GT
Pelley
R
R
Sandstrom
K
K
McLain
D
D
Elson
P
P
Crownover
R
R
Marks
K
K
Muschler
G
G
Joyce
M
M
Zehr
R
R
Bukowski
R
R
D000328:Adult; D000368:Aged; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004337:Drug Carriers; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy*
D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin