1. Multi-centre Phase II trial of the polyamine synthesis inhibitor SAM486A (CGP48664) in patients with metastatic melanoma.
- Author
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Millward MJ, Joshua A, Kefford R, Aamdal S, Thomson D, Hersey P, Toner G, and Lynch K
- Subjects
- Adult, Aged, Amidines adverse effects, Antineoplastic Agents adverse effects, Female, Fluorodeoxyglucose F18, Humans, Indans adverse effects, Karnofsky Performance Status, Male, Melanoma diagnostic imaging, Middle Aged, Neoplasm Metastasis, Positron-Emission Tomography, Radiopharmaceuticals, Adenosylmethionine Decarboxylase antagonists & inhibitors, Amidines therapeutic use, Antineoplastic Agents therapeutic use, Indans therapeutic use, Melanoma drug therapy, Melanoma pathology
- 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.
- Published
- 2005
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