A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1 (GRM1) signaling, in patients with advanced melanoma

Janice M. Mehnert, Ann W. Silk, J. H. Lee, Liesel Dudek, Byeong Seon Jeong, Jiadong Li, Jason M. Schenkel, Evita Sadimin, Michael Kane, Hongxia Lin, Weichung J. Shih, Andrew Zloza, Suzie Chen, James S. Goydos

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg PO bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1-positive tumors were enrolled. No objective responses were observed, and accrual was stopped. Stable disease was noted in six (46%) patients, with one patient on study for 42 weeks. Riluzole was well tolerated, with fatigue (62%) as the most common adverse event. Downregulation of MAPK and PI3K/AKT was noted in 33% of paired tumor biopsies. Hypothesis-generating correlative studies suggested that downregulation of angiogenic markers and increased leukocytes at the active edge of tumor correlate with clinical benefit. Pharmacokinetic analysis showed interpatient variability consistent with prior riluzole studies. Future investigations should interrogate mechanisms of biologic activity and advance the development of agents with improved bioavailability.

Original languageEnglish (US)
Pages (from-to)534-540
Number of pages7
JournalPigment Cell and Melanoma Research
Volume31
Issue number4
DOIs
StatePublished - Jul 2018
Externally publishedYes

Keywords

  • angiogenic factors and receptors
  • clinical trials
  • glutamate
  • melanoma
  • riluzole
  • skin cancers

ASJC Scopus subject areas

  • Oncology
  • General Biochemistry, Genetics and Molecular Biology
  • Dermatology

Fingerprint

Dive into the research topics of 'A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1 (GRM1) signaling, in patients with advanced melanoma'. Together they form a unique fingerprint.

Cite this