Clinical phase I and pharmacokinetic trial of vinorelbine administered as single intravenous bolus every 21 days in cancer patients.

Abstract

We have performed a high-dose clinical and pharmacokinetic trial with vinorelbine administered as a bolus injection every 21 days. The aim was to evaluate a schedule with longer treatment intervals than one week and to determine the toxicity pattern of such a schedule. A total of 13 patients (pts) with solid tumors (non-small-cell lung [3 pts], unknown primary [3 pts], mesothelioma [2 pts], colon/rectum, sarcoma, thyroid, head/neck and cervix [1 pt each]) were entered [9 male, 4 female, median age: 56 years (range: 37-69)]. Dose levels were 35, 40 and 45 mg/m2 with a total of 26 cycles administered. At 40 mg/m2, 2/6 pts developed grade 4 granulocytopenia. 1/1 pt at 45 mg/m2 developed a grade 4 leuko- and granulocytopenia. Non-hematological toxicities were mild to moderate. Neurologic toxicity except for constipation was mild. Constipation occurred at 35 mg/m2 in 1/6 pts WHO grade 4, at 40 mg/m2 in 2/6 pts WHO grade 3 and at 45 mg/m2 in 1/1 pt WHO grade 4 and was due to neurotoxicity. No objective antitumor response was observed. Vinorelbine pharmacokinetics were analysed in whole blood and plasma and were similar to previously published studies using < or = 30 mg/m2. Our results confirm a high affinity of vinorelbine to corpuscular blood elements. We conclude that the MTD of vinorelbine administered once every 21 days as bolus injection is 40 mg/m2, the dose-limiting toxicities are constipation and granulocytopenia and the recommended dose for subsequent Phase II trials is 35 mg/m2.

• Authors: T Schilling, H H Fiebig, S Kerpel-Fronius, B Winterhalter, P Variol, P Tresca, B Heinrich, A R Hanauske
• Journal: Investigational new drugs (Invest New Drugs) Vol. 14 Issue 4 Pg. 371-8 ( 1996) ISSN: 0167-6997 [Print] United States
• PMID: 9157072 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Vinblastine
• Vinorelbine

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, pharmacokinetics)
• Drug Administration Schedule
• Female
• Humans
• Injections, Intravenous
• Male
• Middle Aged
• Neoplasms (drug therapy, metabolism)
• Vinblastine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Vinorelbine