title: Phase I study of vintriptol, a tryptophan ester of vinblastine.
abstract: Vintriptol, a tryptophan ester of vinblastine, is a new vinca alkaloid derivative. Preclinical studies have demonstrated its antitumour activity in a large variety of animal models. In this phase I study, 47 patients with advanced cancer were exposed to escalating doses of vintriptol, starting at 6 mg/m2 and following a modified Fibonacci schedule. The drug was administered as an intravenous push on a weekly schedule. Myelosuppression was the dose-limiting toxicity and the maximum tolerated dose was 45 mg/m2. Other toxicities consisted of mild nausea and vomiting and the occurrence of fever and dryness of the mouth immediately after drug administration. Neurotoxicity, a major side-effect of other vinca alkaloids, was insignificant. 1 partial remission in a patient suffering from colorectal cancer and 1 minor response in a patient with a metastatic tumour of the cutaneous appendagous glands were documented. Pharmacokinetics of vintriptol were evaluated at the highest dose levels. A dose schedule of 40 mg/m2 vintriptol per week is recommended for phase II studies.
authors.affiliation: The Netherlands Cancer Institute, Amsterdam.
authors.forename: H M
authors.initials: HM
authors.lastname: Oosterkamp
authors.forename: L T
authors.initials: LT
authors.lastname: Vlasveld
authors.forename: J
authors.initials: J
authors.lastname: Wanders
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: O
authors.initials: O
authors.lastname: van Tellingen
authors.forename: A C
authors.initials: AC
authors.lastname: Dubbelman
authors.forename: G P
authors.initials: GP
authors.lastname: Simonetti
authors.forename: H R
authors.initials: HR
authors.lastname: Franklin
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: W W
authors.initials: WW
authors.lastname: Ten Bokkel Huinink
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D013921:Thrombocytopenia / Q000139:chemically induced; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C050339:vintriptol; D014747:Vinblastine