Document Detail


Phase I trial of zoledronic acid + imatinib mesylate (Gleevec) in patients with bone metastases.
MedLine Citation:
PMID:  19652577     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Allan Lipton; Cynthia Campbell-Baird; Harold Harvey; Christian Kim; Laurence Demers; Luis Costa
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of clinical oncology     Volume:  33     ISSN:  1537-453X     ISO Abbreviation:  Am. J. Clin. Oncol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-09     Completed Date:  2010-03-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8207754     Medline TA:  Am J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  75-8     Citation Subset:  IM    
Affiliation:
Department of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. alipton@psu.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Bone Neoplasms / drug therapy*,  secondary
Breast Neoplasms / drug therapy*,  pathology
Diphosphonates / administration & dosage
Female
Humans
Imidazoles / administration & dosage
Kidney Neoplasms / drug therapy*,  pathology
Male
Maximum Tolerated Dose
Neoplasm Staging
Piperazines / administration & dosage
Prognosis
Prostatic Neoplasms / drug therapy*,  pathology
Pyrimidines / administration & dosage
Sarcoma / drug therapy*,  secondary
Survival Rate
Treatment Outcome
Chemical
Reg. No./Substance:
0/Diphosphonates; 0/Imidazoles; 0/Piperazines; 0/Pyrimidines; 118072-93-8/zoledronic acid; 152459-95-5/imatinib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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