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


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.
Millward
Michael J
MJ
Sydney Cancer Centre & Sydney Melanoma Unit, Royal Prince Alfred Hospital, Sydney, Australia. millward@cyllene.uwa.edu.au
Joshua
Anthony
A
Kefford
Rick
R
Aamdal
Steinar
S
Thomson
Damien
D
Hersey
Peter
P
Toner
Guy
G
Lynch
Kevin
K
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000328:Adult; D000368:Aged; D000578:Amidines / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D017567:Karnofsky Performance Status; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
D000578:Amidines; D000970:Antineoplastic Agents; D007189:Indans; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C082408:4-amidinoindan-1-one 2'-amidinohydrazone; D012437:Adenosylmethionine Decarboxylase