Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS malignancy consortium protocol 042

Henry B. Koon, Susan E. Krown, Jeannette Y. Lee, Kord Honda, Suthee Rapisuwon, Zhenghe Wang, David Aboulafia, Erin G. Reid, Michelle A. Rudek, Bruce J. Dezube, Ariela Noy

Research output: Contribution to journalArticlepeer-review

Abstract

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 in patients 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.

Original languageEnglish (US)
Pages (from-to)402-408
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number5
DOIs
StatePublished - Feb 10 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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