A multicenter Phase II study of bortezomib in recurrent or metastatic sarcomas

Maki, R. G., Kraft, A. S., Scheu, K., Yamada, J., Wadler, S., Antonescu, C. R., Wright, J. J., Schwartz, G. K. (April 2005) A multicenter Phase II study of bortezomib in recurrent or metastatic sarcomas. Cancer, 103 (7). pp. 1431-8. ISSN 0008-543X (Print)0008-543X (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/15739208
DOI: 10.1002/cncr.20968

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Antineoplastic Agents/*therapeutic use Bone Neoplasms/*drug therapy Boronic Acids/adverse effects/*therapeutic use Bortezomib Drug Administration Schedule Fatigue/chemically induced Female Humans Male Middle Aged Neoplasm Metastasis/drug therapy Neoplasm Recurrence, Local/drug therapy Nervous System Diseases/chemically induced *Proteasome Inhibitors Pyrazines/adverse effects/*therapeutic use Sarcoma/*drug therapy/pathology Soft Tissue Neoplasms/*drug therapy Treatment Outcome
Subjects: diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > metastasis
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 1 April 2005
Date Deposited: 26 Oct 2016 20:33
Last Modified: 26 Oct 2016 20:33
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33661

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