Phase I and clinical pharmacology study of trimetrexate administered weekly for three weeks.

Published

Journal Article

Trimetrexate, a new antifolate compound, was administered by 30-min infusions weekly for 3 weeks to 29 patients with solid tumors in a Phase I study. Thrombocytopenia was dose limiting, but highly variable among patients at a given dose level; other toxicity was mild and uncommon. Twenty-three patients participated in pharmacokinetic studies and five patients participated in a study of the effects of trimetrexate on [6-3H]-deoxyuridine incorporation into hematopoietic cell DNA. The median total body clearance of trimetrexate for each dose level was independent of dose but the total body clearance varied widely among patients at a given dose level. The magnitude of the fall in platelet count in individual patients correlated well with the amount of exposure to trimetrexate, but not with the extent of prior therapy. The amount of [6-3H]deoxyuridine incorporation into hematopoietic cell DNA at 72 h after drug administration correlated with the total body clearance of trimetrexate. The total body clearance of trimetrexate was reduced in patients with impaired hepatic synthetic function, as judged by low pretreatment serum albumin concentrations. The recommended Phase II starting dose on this schedule is 130 mg/m2 weekly for 3 weeks; patients with hypoalbuminemia should be treated at lower doses.

Full Text

Duke Authors

Cited Authors

  • Fanucchi, MP; Walsh, TD; Fleisher, M; Lokos, G; Williams, L; Cassidy, C; Vidal, P; Chou, TC; Niedzwiecki, D; Young, CW

Published Date

  • June 15, 1987

Published In

Volume / Issue

  • 47 / 12

Start / End Page

  • 3303 - 3308

PubMed ID

  • 2953412

Pubmed Central ID

  • 2953412

International Standard Serial Number (ISSN)

  • 0008-5472

Language

  • eng

Conference Location

  • United States