Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. Academic Article Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Anti-HIV Agents
  • Cytokines
  • Disease Progression
  • Female
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Pilot Projects
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor beta
  • Time Factors
  • Treatment Outcome
  • United States

MeSH Major

  • AIDS-Related Opportunistic Infections
  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sarcoma, Kaposi

abstract

  • 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. 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. 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. 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.

publication date

  • February 10, 2014

has subject area

  • AIDS-Related Opportunistic Infections
  • Adult
  • Aged
  • Anti-HIV Agents
  • Antineoplastic Agents
  • Benzamides
  • Cytokines
  • Disease Progression
  • Female
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Pilot Projects
  • Piperazines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-kit
  • Pyrimidines
  • Receptor, Platelet-Derived Growth Factor beta
  • Sarcoma, Kaposi
  • Time Factors
  • Treatment Outcome
  • United States

Research

keywords

  • Clinical Trial, Phase II
  • Journal Article
  • Multicenter Study

Identity

Language

  • eng

PubMed Central ID

  • PMC3912327

Digital Object Identifier (DOI)

  • 10.1200/JCO.2012.48.6365

PubMed ID

  • 24378417

Additional Document Info

start page

  • 402

end page

  • 408

volume

  • 32

number

  • 5