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A multicenter Phase II study of bortezomib in recurrent or metastatic sarcomas†
Version of Record online: 28 FEB 2005
Copyright © 2005 American Cancer Society
Volume 103, Issue 7, pages 1431–1438, 1 April 2005
How to Cite
Maki, R. G., Kraft, A. S., Scheu, K., Yamada, J., Wadler, S., Antonescu, C. R., Wright, J. J. and Schwartz, G. K. (2005), A multicenter Phase II study of bortezomib in recurrent or metastatic sarcomas. Cancer, 103: 1431–1438. doi: 10.1002/cncr.20968
Presented, in part, at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, May 31–June 3, 2003 (abstract 3291).
- Issue online: 18 MAR 2005
- Version of Record online: 28 FEB 2005
- Manuscript Accepted: 29 NOV 2004
- Manuscript Received: 17 NOV 2004
- National Cancer Institute (CTEP protocol 1757). Grant Numbers: P01-CA47179, N01-CM17105
- Robert and Deborah Bloch Sarcoma Research Fund
- Phase II;
Based on evidence of activity in preclinical and Phase I studies, the authors undertook a study of bortezomib, a reversible proteasome inhibitor, for patients with metastatic sarcomas.
Two arms were opened, each using a Simon two-stage design. Arm A included patients with osteogenic sarcoma, Ewing sarcoma, and rhabdomyosarcoma. Arm B accrued patients with other types of soft tissue sarcomas. Patients were not allowed to have received previous chemotherapy for metastatic disease. The initial dose of bortezomib was a 1.5 mg/m2 intravenous push twice weekly followed by a rest week. The dose was escalated to 1.7 mg/m2 if patients tolerated Cycle 1 well. The dose escalation was eliminated due to toxicity observed in the first six patients.
Painful neuropathy, myalgias, and asthenia were the most significant observed toxicities. The most frequent toxicities included fatigue, diarrhea, constipation, and nausea. Pharmacodynamic data from 18 patients with complete data collection did not show consistent differences between patients with or without Grade 2 or Grade 3 neuropathy (toxicity graded according the National Cancer Institute Common Toxicity Criteria). Arm A had low accrual and was closed. One confirmed partial response among 21 evaluable patients was observed on Arm B in a patient with leiomyosarcoma. Due to the inactivity of this agent, the study was closed after the first stage of accrual.
Bortezomib has minimal activity in soft tissue sarcoma as a single agent. If studied further in sarcomas, bortezomib should be investigated in combination with agents with demonstrated preclinical synergy. Cancer 2005. © 2005 American Cancer Society.