Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: from the AIDS Malignancy Consortium and IM862 Study Team. Academic Article Article uri icon

Overview

MeSH

  • Administration, Intranasal
  • Adult
  • Aged
  • CD4 Lymphocyte Count
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Remission Induction
  • Self Administration
  • Viral Load

MeSH Major

  • AIDS-Related Opportunistic Infections
  • Acquired Immunodeficiency Syndrome
  • Angiogenesis Inhibitors
  • Anti-HIV Agents
  • Dipeptides
  • Sarcoma, Kaposi

abstract

  • IM862 is a synthetic dipeptide (L-glutamine L-tryptophan) with in vitro and in vivo antiangiogenic properties. Phase I/II studies showed minimal toxicity and a response rate of 36% in AIDS-Kaposi's sarcoma. We report a 24-week, randomized, double-blinded, placebo-controlled phase III trial with the phase II dose, 5 mg intranasally every other day. Two hundred two HIV-positive patients were enrolled, 104 on IM862 and 98 on placebo. Baseline characteristics were comparable except current antiretroviral therapy: 88% versus 96% (IM862 v placebo group; P = .042). The median treatment durations were 19.5 versus 24 weeks (IM862 v placebo). No significant difference was detected in response rate (IM862, 23%; 95% CI, 15% to 32% v placebo, 21%; 95% CI, 14% to 31%; P = .46), time to response (8.5 weeks v 14 weeks; P = .024), or duration of response. However, IM862 was associated with both a shorter time to response (8.5 weeks v 14 weeks; P = .024) and shorter median time to progression (16 weeks, 95% CI, 13 to 27 weeks v 35 weeks, 95% CI, 26 to 114 weeks; P = .012). Despite promising phase I and phase II studies, IM862 5 mg every other day was not superior to placebo and may accelerate time to progression. Highly active antiretroviral therapy alone was associated with a substantial rate of sustained tumor response and may have contributed to prior estimates of IM862 response. Therapeutic trials for AIDS-Kaposi's sarcoma must account for ongoing immune reconstitution in the setting of concurrent highly active antiretroviral therapy that may confound estimates of therapeutic activity.

publication date

  • February 10, 2005

has subject area

  • AIDS-Related Opportunistic Infections
  • Acquired Immunodeficiency Syndrome
  • Administration, Intranasal
  • Adult
  • Aged
  • Angiogenesis Inhibitors
  • Anti-HIV Agents
  • CD4 Lymphocyte Count
  • Dipeptides
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Remission Induction
  • Sarcoma, Kaposi
  • Self Administration
  • Viral Load

Research

keywords

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1200/JCO.2005.11.043

PubMed ID

  • 15598977

Additional Document Info

start page

  • 990

end page

  • 998

volume

  • 23

number

  • 5