A multicenter phase II study of bortezomib in recurrent or metastatic sarcomas Journal Article
| Authors: | Maki, R. G.; Kraft, A. S.; Scheu, K.; Yamada, J.; Wadler, S.; Antonescu, C. R.; Wright, J. J.; Schwartz, G. K. |
| Article Title: | A multicenter phase II study of bortezomib in recurrent or metastatic sarcomas |
| Abstract: | BACKGROUND. Based on evidence of activity in preclinical and Phase 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, con-stipation, 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. © 2005 American Cancer Society. |
| Keywords: | osteosarcoma; adult; clinical article; treatment outcome; aged; bone neoplasms; middle aged; clinical trial; constipation; fatigue; doxorubicin; diarrhea; side effect; antineoplastic agents; cancer staging; recurrent cancer; edema; bortezomib; proteasome; proteasome inhibitor; infection; pain; phase 2 clinical trial; boronic acids; neoplasm recurrence, local; proteasome endopeptidase complex; pyrazines; neuropathy; stomatitis; myalgia; drug administration schedule; cancer pain; deep vein thrombosis; antineoplastic activity; ifosfamide; abdominal pain; arthralgia; asthenia; coughing; dizziness; dyspnea; ewing sarcoma; fever; pruritus; rash; sarcoma; alkaline phosphatase; insomnia; thorax pain; multicenter study; neoplasm metastasis; urinary frequency; soft tissue sarcoma; heartburn; headache; rhabdomyosarcoma; dyspepsia; flatulence; phase ii; abdominal cramp; prochlorperazine; dose calculation; soft tissue neoplasms; pharmacokinetics; nervous system diseases; conjunctivitis |
| Journal Title: | Cancer |
| Volume: | 103 |
| Issue: | 7 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2005-04-01 |
| Start Page: | 1431 |
| End Page: | 1438 |
| Language: | English |
| DOI: | 10.1002/cncr.20968 |
| PUBMED: | 15739208 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - Presented, in part, at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, May 31–June 3, 2003 (abstract 3291) - "Cited By (since 1996): 39" - "Export Date: 24 October 2012" - "CODEN: CANCA" - "Source: Scopus" |
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