Multi-centre Phase II trial of the polyamine synthesis inhibitor SAM486A (CGP48664) in patients with metastatic melanoma

Michael J. Millward*, Anthony Joshua, Rick Kefford, Steinar Aamdal, Damien Thomson, Peter Hersey, Guy Toner, Kevin Lynch

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: To determine the activity and tolerability of SAM496A, an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), in patients with metastatic melanoma who had not received prior chemotherapy. Selected patients were offered participation in two sub-studies examining early changes in tumor metabolism with FDG-PET and changes in tumor polyamine content. Patients and methods: Fifteen patients with measurable metastatic melanoma, normal cardiac function, and no known CNS metastases were eligible and received SAM486A by 1-hour IV infusion daily for 5 days every 3 weeks. Response was assessed by SWOG criteria. Results: No patient had a confirmed partial response. Fatigue/lethargy, myalgia and neutropenia were the main toxicities but no febrile neutropenia or grade 4 non-hematological toxicity occurred. Five patients had PET scans pre-treatment and on days 8-12 of cycle 1. No patient had reduction of tumor metabolism. Serial biopsy in one patient showed alterations in polyamines consistent with SAMDC inhibition. Conclusions: Using the present dose and schedule of administration, SAM486A does not have significant therapeutic potential in patients with metastatic melanoma.

Original languageEnglish
Pages (from-to)253-256
Number of pages4
JournalInvestigational New Drugs
Volume23
Issue number3
DOIs
Publication statusPublished - Jun 2005
Externally publishedYes

Keywords

  • Melanoma
  • PET scanning
  • Polyamines

Fingerprint Dive into the research topics of 'Multi-centre Phase II trial of the polyamine synthesis inhibitor SAM486A (CGP48664) in patients with metastatic melanoma'. Together they form a unique fingerprint.

Cite this