| Title: |
A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours |
| Authors: |
Paridaens, R; Uges, DRA; Barbet, N; Choi, L; Seeghers, M; van der Graaf, WTA; Groen, HJM; Dumez, H; Van Buuren, I; Muskiet, F; Capdeville, R; van Oosterom, AT; de Vries, EGE |
| Source: |
Paridaens, R, Uges, DRA, Barbet, N, Choi, L, Seeghers, M, van der Graaf, WTA, Groen, HJM, Dumez, H, Van Buuren, I, Muskiet, F, Capdeville, R, van Oosterom, AT & de Vries, EGE 2000, 'A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours', British Jounal of Cancer, vol. 83, no. 5, pp. 594-601. https://doi.org/10.1054/bjoc.2000.1305 |
| Publication Year: |
2000 |
| Collection: |
University of Groningen research database |
| Subject Terms: |
polyamine; SAMDC; phase I; 5FU; neutropenia; S-ADENOSYLMETHIONINE DECARBOXYLASE; ENZYME TARGET; CHROMATOGRAPHY; THERAPY; GROWTH |
| Description: |
Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), more potent and specific than the first-generation SAMDC inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing confirmed promising antiproliferative activity. In this phase I study, SAM486A was given 4-weekly as a 120 h infusion. 39 adult cancer patients were enrolled with advanced/refractory disease not amenable to established treatments, PS less than or equal to 2, adequate marrow, liver, renal and cardiac function. Doses were escalated in 100% increments without toxicity in 24 pts from 3 mg m(-2) cycle(-1) up to 400 mg m(-2) cycle(-1). At 550 and 700 mg m(-2) cycle(-1) reversible dose-limiting neutropenia occurred. Other toxicities included mild fatigue, nausea and vomiting. No objective remission was seen. Pharmakokinetic analysis showed a terminal half-life of approximately 2 days. AUG and Cmax were related to dose; neutropenia correlated with AUG. The recommended dose for further phase II studies on this schedule is 400 mg m(-2) cycle(-1). (C) 2000 Cancer Research Campaign. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0007-0920 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/10944598; info:eu-repo/semantics/altIdentifier/wos/000088909400008; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/11370/a9f5b412-43ff-49d8-99fd-f56846fe9283; info:eu-repo/semantics/altIdentifier/pissn/0007-0920 |
| DOI: |
10.1054/bjoc.2000.1305 |
| Availability: |
https://hdl.handle.net/11370/a9f5b412-43ff-49d8-99fd-f56846fe9283; https://research.rug.nl/en/publications/a9f5b412-43ff-49d8-99fd-f56846fe9283; https://doi.org/10.1054/bjoc.2000.1305; https://pure.rug.nl/ws/files/62261558/A_phase_I_study_of_a_new_polyamine_biosynthesis_inhibitor.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| Accession Number: |
edsbas.2E6DEE37 |
| Database: |
BASE |