| Autor: |
Eskens, FALM, Greim, GA, van Zuylen, C, Wolff, [No Value], Denis, LJ, Planting, AST, Muskiet, FA, Barbet, NC, Choi, L, Capdeville, R, Verweij, J, Hanauske, AR, Bruntsch, U |
| Přispěvatelé: |
Faculteit Medische Wetenschappen/UMCG, Lifestyle Medicine (LM) |
| Jazyk: |
angličtina |
| Rok vydání: |
2000 |
| Předmět: |
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| Zdroj: |
Clinical Cancer Research, 6(5), 1736-1743. AMER ASSOC CANCER RESEARCH |
| ISSN: |
1078-0432 |
| Popis: |
A single-agent dose-escalating Phase I and pharmacological study of the polyamine synthesis inhibitor SAM 486A was performed. A dosing regimen of four weekly infusions followed by 2 weeks off therapy was studied. Fifty patients were entered into the study. Dose levels studied were 1.25, 2.5, 5, 8, 16, 32, 48, 70, 110, 170, 270, and 325 mg/m(2)/week. Pharmacokinetic sampling was done on day 1, and trough samples were taken weekly during the first treatment cycle. Pharmacodynamic sampling was done on days 1 and 22, At 325 mg/m(2)/week, dose-limiting toxicity was seen (one patient each with grade 4 febrile neutropenia, grade 3 neurotoxicity, and grade 3 hypotension with syncope and T-wave inversions on electrocardiogram). The recommended dose for further testing was set at 270 mg/m(2)/week, Infusion time was increased from 10 to 180 min due to facial paresthesias and flushing and somnolence. Drug exposure increased linearly with dose. Mean +/- SD t(1/2) at 70-325 mg/m(2) doses was 61.4 +/- 26.2 h, with a large volume of distribution at steady state. In peripheral blood leukocytes, a clear relationship between dose and inhibitory effect on S-adenosylmethionine decarboxylase or changes in intracellular polyamine pools was not recorded. SAM 386A can be administered safely using a dosing regimen of four weekly infusions followed by 2 weeks off therapy. The recommended dose for Phase II studies using this regimen is 270 mg/m(2)/week. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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