科研之友
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摘要
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 I 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.
- 出版日期2010-2-10
