Combining drugs with known single-agent activity that lack overlapping dose-limiting toxicities and exert antitumor activity through different mechanisms could improve clinical outcome. As toceranib and vinblastine meet these requisites, a phase I trial was performed on the combination in dogs with mast cell tumors. The dose-limiting toxicity for the simultaneous combination was neutropenia and the maximally tolerated dose was vinblastine (1.6 mg/m2 every other week) concurrent with toceranib (3.25 mg/kg PO, every other day). This represents greater than a 50% reduction in dose-intensity for vinblastine (compared to single-agent use) and as such does not support this combination based on current drug combination paradigms. While a strict adherence to dose paradigms speaks against the combination, evidence of significant activity (71% objective response) and enhanced myelosuppression suggest additive or synergistic activity. A prospective randomized evaluation comparing this combination with standard single-agent treatments would seem prudent to interrogate this potential.
Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events.
Background: The safety of IV administration of docetaxel to cats with cancer has not been reported. Objectives: Document adverse effects of IV administration of docetaxel to cats. Animals: Twenty-one client-owned cats with any confirmed malignancy. Methods: Cats received up to 5 docetaxel treatments, administered IV every 3 weeks. The initial dosage was 1.0 mg/kg, and dosages were increased by increments of 0.25 mg/kg in cohorts of 3 cats. Adverse events were determined by a CBC at days 7 and 21, serum chemistry and urine specific gravity at day 21, and medical histories provided by the owners.Results: Cats received docetaxel dosages ranging from 1.0 to 2.5 mg/kg, for a median of 2 treatments. Dose-limiting toxicoses included fever, neutropenia, and vomiting, seen in 2 of the 4 cats treated at 2.5 mg/kg. Hypersensitivity reactions were infrequent (4 of the 21 cats) and mild. The maximum tolerated dosage was 2.25 mg/kg.Conclusions and Clinical Importance: Docetaxel can be administered IV to cats with a low incidence of adverse effects.
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