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Medline ® Abstract for Reference 57

of 'AIDS-related Kaposi sarcoma: Staging and treatment'

57
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Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042.
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Koon HB, Krown SE, Lee JY, Honda K, Rapisuwon S, Wang Z, Aboulafia D, Reid EG, Rudek MA, Dezube BJ, Noy A
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J Clin Oncol. 2014;32(5):402. Epub 2013 Dec 30.
 
PURPOSE: Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients.
PATIENTS AND METHODS: This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics inpatients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable.
RESULTS: Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines.
CONCLUSION: Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS.
AD
Henry B. Koon and Zhenghe Wang, Case Comprehensive Cancer Center, Case Western Reserve University; Kord Honda, University Hospitals; Cleveland, OH; Susan E. Krown, Ariela Noy, Memorial Sloan-Kettering Cancer Center, New York, NY; Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR; Suthee Rapisuwon, Georgetown University Medical Center, Washington, DC; David Aboulafia, Virginia Mason Medical Center, Seattle, WA; Erin G. Reid, University of California San Diego Moores Cancer Center, San Diego, CA; Michelle A. Rudek, Johns Hopkins University, Baltimore, MD; Bruce J Dezube, Beth Israel Deaconess Medical Center, Boston, MA.
PMID