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Investigational New Drugs

, Volume 23, Issue 3, pp 253–256 | Cite as

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

  • Michael J. MillwardEmail author
  • Anthony Joshua
  • Rick Kefford
  • Steinar Aamdal
  • Damien Thomson
  • Peter Hersey
  • Guy Toner
  • Kevin Lynch
Article

Summary

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.

Key words

melanoma polyamines PET scanning 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Michael J. Millward
    • 1
    • 8
    Email author
  • Anthony Joshua
    • 1
  • Rick Kefford
    • 2
  • Steinar Aamdal
    • 3
  • Damien Thomson
    • 4
  • Peter Hersey
    • 5
  • Guy Toner
    • 6
  • Kevin Lynch
    • 7
  1. 1.Sydney Cancer Centre & Sydney Melanoma UnitRoyal Prince Alfred HospitalSydneyAustralia
  2. 2.Westmead Hospital & Sydney Melanoma UnitSydneyAustralia
  3. 3.The Norwegian Radium HospitalOsloNorway
  4. 4.Princess Alexandra HospitalBrisbaneAustralia
  5. 5.Royal Newcastle Hospital & Sydney Melanoma UnitNewcastleAustralia
  6. 6.Peter MacCallum Cancer InstituteMelbourneAustralia
  7. 7.Novartis Pharma Pty LtdSydneyAustralia
  8. 8.School of Medicine and PharmacologySir Charles Gairdner Hospital Unit M503PerthAustralia

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