Phase I study of vintriptol, a tryptophan ester of vinblastine.
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.
Oosterkamp
H M
HM
The Netherlands Cancer Institute, Amsterdam.
Vlasveld
L T
LT
Wanders
J
J
Beijnen
J H
JH
van Tellingen
O
O
Dubbelman
A C
AC
Simonetti
G P
GP
Franklin
H R
HR
Vermorken
J B
JB
Ten Bokkel Huinink
W W
WW
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
D000970:Antineoplastic Agents; C050339:vintriptol; D014747:Vinblastine