MG98, a second-generation DNMT1 inhibitor, in the treatment of advanced renal cell carcinoma

Cancer Invest. 2012 Jun;30(5):415-21. doi: 10.3109/07357907.2012.675381.

Abstract

Background: In carcinogenesis, methylation of DNA promoter regions results in inactivation of tumor-suppressing genes. MG98 was designed to inhibit DNA methyltransferases enzyme 1 production.

Methods: This multicenter study explored two schedules of MG98 with Interferon-α-2β to identify schedule and dose for patients with metastatic RCC.

Results: Doses of IFN 9 MIU/MG98 125 mg/m(2) for a continuous schedule and IFN 9 MIU/MG98 200 mg/m(2) for an intermittent schedule were considered the MTDs. Treatment resulted in one PR and eight SD.

Conclusion: MG98 combined with IFN was safe and resulted in clinical activity.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
  • Disease-Free Survival
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Middle Aged
  • Oligodeoxyribonucleotides / adverse effects
  • Oligodeoxyribonucleotides / therapeutic use*
  • Thionucleotides / adverse effects
  • Thionucleotides / therapeutic use*

Substances

  • MG 98 phosphorothioate antisense oligodeoxynucleotide
  • Oligodeoxyribonucleotides
  • Thionucleotides
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human