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Phase II Trial of Liposomal Doxorubicin (Doxil®) in Advanced Soft Tissue Sarcomas

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Abstract

Purpose: To assess the objective response rate, toxicityexperienced, progression-free survival, and overall survival ofpatients with previously untreated advanced soft tissue sarcomastreated with a liposomal doxorubicin formulation (Doxil).

Methods: Patients with metastatic or recurrent soft tissuesarcoma who had received no prior chemotherapy for advanceddisease were treated with liposomal doxorubicin (Doxil) accordingto a two stage accrual design. Doxil was administered at 50mg/m2 every 4 weeks. A total of 15 patients were treated andare evaluable for response and toxicity.

Results: The male/female ratio was 7/8, the median age was60 years (34–75) and the ECOG performance status was 0-1 in>90% of patients. Leiomyosarcoma (7/15) and malignant fibroushistiocytoma (2/15) were the most common histologic diagnoses.No objective responses were observed in the 15 evaluablepatients. No lethal toxicity occurred. Grade 3–4 leukopenia orneutropenia were reported in 3/15 (20%) patients. Grade 3mucositis or hand-foot syndrome occurred in 2/15 (13%) and 1/15(7%) patients respectively and seemed more severe in olderpatients. The median time to progression was 1.9 months (range0.9–6.2). Twelve patients have now died. The Kaplan-Meierestimate of median overall survival is 12.3 months. As called forin the study design, accrual was terminated because no responseswere obtained in the first 15 patients.

Conclusion: Though well-tolerated, Doxil given accordingto this dose and schedule to patients with advanced soft tissuesarcoma had no significant therapeutic activity. A correlationbetween older age and skin/mucosal toxicity of Doxil is suggestedin this study but needs confirmation. Future investigations ofDoxil in soft tissue sarcomas should use a different schedule anddose.

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Authors and Affiliations

  1. The Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USA

    T. Chidiac, G.T. Budd, R. Pelley, K. Sandstrom, D. McLain, P. Elson, R. Crownover, K. Marks, G. Muschler, M. Joyce, R. Zehr & R. Bukowski

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  1. T. Chidiac
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  2. G.T. Budd
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  3. R. Pelley
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  4. K. Sandstrom
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  5. D. McLain
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  6. P. Elson
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  7. R. Crownover
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  8. K. Marks
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  9. G. Muschler
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  10. M. Joyce
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  11. R. Zehr
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  12. R. Bukowski
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Chidiac, T., Budd, G., Pelley, R. et al. Phase II Trial of Liposomal Doxorubicin (Doxil®) in Advanced Soft Tissue Sarcomas. Invest New Drugs 18, 253–259 (2000). https://doi.org/10.1023/A:1006429907449

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