A phase I and pharmacokinetic study of intravenous vinzolidine

• Published in: Investigational new drugs Vol. 8; no. S1; pp. S51 - S57
• Main Authors: TAYLOR, C. W, SALMON, S. E, SATTERLEE, W. G, ROBERTONE, A. B, MCCLOSKEY, T. M, HOLDSWORTH, M. T, PLEZIA, P. M, ALBERTS, D. S
• Format: Journal Article
• Language: English
• Published: Dordrecht Kluwer 01-01-1990
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; Biological and medical sciences; Chemotherapy; Drug Evaluation; Female; Humans; Injections, Intravenous; Male; Medical sciences; Middle Aged; Neoplasms - drug therapy; Pharmacology. Drug treatments; Vinca Alkaloids - administration & dosage; Vinca Alkaloids - pharmacokinetics; Vinca Alkaloids - therapeutic use; Vinca Alkaloids - toxicity; Antineoplastic agent; Human; Urinary system disease; Intravenous administration; Melanoma; Tolerance; Kidney; Alkaloid; Chemotherapy; Treatment; Phase I trial; Tumor; Pharmacokinetics
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/BF00171984

The semi-synthetic vinca alkaloid vinzolidine was administered to advanced cancer patients as an intravenous bolus on a three day schedule every 21 days. Forty-two patients were treated in this phase I trial. Five partial remissions (breast--1, melanoma--2, renal cancer--2) were seen in 30 evaluable patients. The dose limiting toxicities were myelosuppression and neuropathy. Erratic myelosuppression from course to course within the same patient as seen in previous trials with oral vinzolidine, was not observed with the intravenous formulation. The measured pharmacokinetic parameters conformed best to a 2-compartment model with a mean terminal half-life of 23 hours. The anti-tumor activity observed during this phase I trial and acceptable toxicity provide the basis for initiating phase II studies in selected forms of cancer.