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Phase II Study of Doxorubicin and Bevacizumab for Patients With Metastatic Soft-Tissue Sarcomas

From the Gastrointestinal Oncology Service and Developmental Chemotherapy Service, Department of Medicine and Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT; and Investigational Drug Branch, Clinical Trials Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD

Address reprint requests to David D'Adamo, MD, PhD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: dadamod{at}mskcc.org

PURPOSE: To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS).

PATIENTS AND METHODS: Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m² intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m².

RESULTS: A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m² doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m², respectively), one grade 3 (total doxorubicin 591 mg/m²), and one grade 4 (total doxorubicin 420 mg/m²). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related.

CONCLUSION: The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

Supported in part by Grants No. PPG P01 CA47179 and N01-CM17105, as well as the Dibner Fund for Sarcoma Research and Abolish Cancer Today.

D.R.D. and S.E.A. contributed equally to this study.

This study was presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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