Ridaforolimus: a promising drug in the treatment of soft-tissue sarcoma and other malignancies

Future Oncol. 2011 Jul;7(7):827-39. doi: 10.2217/fon.11.57.

Abstract

Ridaforolimus (deforolimus; AP23573; MK-8669) is a novel sirolimus derivative manufactured by ARIAD Pharmaceuticals and acquired by Merck. It is a small-molecule kinase inhibitor of the mTOR in clinical development for the treatment of cancer. Both intravenous and oral formulations of the agent are being tested in cancer clinical trials. In preclinical and clinical studies, ridaforolimus exhibited significant antitumor activity with acceptable safety and tolerability. With single-agent ridaforolimus, mucositis and myelosuppression were dose-limiting toxicities. In advanced soft-tissue sarcoma, single-agent ridaforolimus was associated with a 29% clinical benefit rate and 2% partial response rate. A Phase III trial has recently been reported to have met its primary end point.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Approval / legislation & jurisprudence
  • Drug Evaluation, Preclinical
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Sarcoma / drug therapy*
  • Sarcoma / enzymology
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / chemistry
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • ridaforolimus
  • TOR Serine-Threonine Kinases
  • Sirolimus