Phase I trial of zoledronic acid + imatinib mesylate (Gleevec) in patients with bone metastases

Allan Lipton, Cynthia Campbell-Baird, Harold Harvey, Christian Kim, Laurence Demers, Luis Costa

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Objectives and Methods: Patients with bone metastases suffer from long-term skeletal morbidity and a reduction in quality of life. Treatment consists of radiation or surgery to prevent or repair fractures and bisphosphonates to delay skeletal-related events (SRE). Platelet-derived growth factor released from metastatic cancer cells may influence the development and progression of bone metastases. Imatinib mesylate (Gleevec) inhibits platelet-derived growth factor-receptor tyrosine kinase signaling, increases apoptosis, reduces proliferation, and lowers microvessel density in human tumors. This phase I study assessed the effects of the combination of zoledronic acid (a bisphosphonate used to delay SRE) and Gleevec on 15 evaluable patients with osteolytic or osteoblastic bone metastases. Results: Although 6 of 9 patients noted an improvement in pain and 1 patient was stable, the quality of life improved in only 3 patients. Dose limiting toxicity was observed in 0 of 5 (400 mg Gleevec), 2 of 5 (600 mg), and 4 of 5 (800 mg) patients. Although no patient required radiation and only 2 SRE occurred during the study, disease progression in bone and/or extraskeletal sites occurred in most patients. Conclusion: The combination of zoledronic acid + Gleevec is not recommended in patients with bone metastases because of toxicity and limited clinical efficacy.

Original languageEnglish (US)
Pages (from-to)75-78
Number of pages4
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume33
Issue number1
DOIs
StatePublished - Feb 1 2010

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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