Phase I and clinical pharmacology study of trimetrexate administered weekly for three weeks Journal Article
| Authors: | Fanucchi, M. P.; Walsh, T. D.; Fleisher, M.; Lokos, G.; Williams, L.; Cassidy, C.; Vidal, P.; Chou, T. C.; Niedzwiecki, D.; Young, C. W. |
| Article Title: | Phase I and clinical pharmacology study of trimetrexate administered weekly for three weeks |
| Abstract: | 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. © 1987, American Association for Cancer Research. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; clinical article; aged; middle aged; unclassified drug; drug efficacy; skin toxicity; solid tumor; dna synthesis; adenocarcinoma; liver toxicity; nephrotoxicity; bone marrow; mucosa inflammation; thrombocytopenia; lung neoplasms; hypoalbuminemia; kinetics; hematopoietic cell; hematopoietic stem cells; drug clearance; drug dose; phase 1 clinical trial; chromatography, high pressure liquid; radioisotope; drug therapy; quinazolines; adverse drug reaction; therapy; drug protein binding; intravenous drug administration; pharmacokinetics; mathematics; trimetrexate; drug evaluation; intoxication; humans; human; female; priority journal; deoxyuridine; blood and hemopoietic system; deoxyuridine h 3 |
| Journal Title: | Cancer Research |
| Volume: | 47 |
| Issue: | 12 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1987-06-15 |
| Start Page: | 3303 |
| End Page: | 3308 |
| Language: | English |
| PUBMED: | 2953412 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 February 2021 -- Source: Scopus |
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