Phase I clinical trial of vinorelbine in tumor-bearing cats.

BACKGROUND: Vinorelbine (VRL) has been investigated in dogs, but its use in cats has not been studied.

HYPOTHESIS/OBJECTIVES: To determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of VRL in tumor-bearing cats.

ANIMALS: Cats were included in this prospective phase I trial if they had confirmed malignancy, received ≥1 VRL treatment, and had adequate follow-up. Previous treatment was acceptable, but concurrent chemotherapy or radiotherapy was not permitted.

METHODS: Using a modified phase I design, cats were enrolled in cohorts of 3 at a starting dosage of 9 mg/m(2) . Cats tolerating the first treatment well were eligible to receive additional VRL treatments at escalating dosages; escalations beyond the perceived MTD were permitted based on individual tolerance. Intended treatment interval was 7 days. Patient histories, physical examinations, and complete blood counts were performed weekly.

RESULTS: Nineteen cats were included. Sixty-one VRL treatments were administered. Median number of treatments was 2 (range, 1-9). Starting dosages were 9-12 mg/m(2) . Maximal dosage administered was 15.5 mg/m(2) . The MTD was 11.5 mg/m(2) . Acute DLTs were neutropenia, vomiting, and nephrotoxicity. Other notable toxicities were weight loss and anemia.

CONCLUSIONS AND CLINICAL IMPORTANCE: Vinorelbine is tolerated in cats at a weekly interval. Recommended starting dosage is 11.5 mg/m(2) . Neutropenia was transient, lasting <7 days; vomiting was self-limiting in most cases. Although VRL-associated nephrotoxicity has not been reported, potential attribution of this toxicity to VRL must not be discounted. Further investigation of the efficacy of VRL in feline malignancies is warranted.