Cabazitaxel Causes a Dose-dependent Central Nervous System Toxicity in Rats

Background: Chemotherapeutic agents may lead to serious neurological side effects, which in turn can deteriorate the quality of life and cause dose limiting. Direct toxic effect or metabolic derangement of chemotherapeutic agents may cause these complications. Cabazitaxel is a next generation semi-synthetic taxane derivative, which is effective in both preclinical models of human tumors sensitive or resistant to chemotherapy and in patients with progressive prostate cancer despite docetaxel treatment.

Aim: The primary aim of this study was to investigate the central nervous system toxicity of Cabazitaxel. Secondary aim was to investigate the safety dose of Cabazitaxel for the central nervous system.

Methods: A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups as follows: group 1 (Controls), group 2 (Cabazitaxel 0.5mg/kg), group 3 (Cabazitaxel 1.0mg/kg) and group 4 (Cabazitaxel 1.5mg/kg). Cabazitaxel (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to groups 2, 3 and 4 at 0.5, 1.0 and 1.5mg/kg (body-weight/week) doses, respectively for four consecutive weeks. Beside this, group 1 received only i.p. saline at the same volume and time. At the end of the study, animals were sacrificed and bilateral brain hemispheres were removed for biochemical, histopathological and immunohistochemical examinations.

Results: Intraperitoneal administration of Cabazitaxel has exerted neurotoxic effect on rat brain. We have observed that biochemical and immunohistochemical results became worse in a dose dependent manner.

Conclusion: Our findings have suggested that Cabazitaxel may be a neurotoxic agent and can trigger apoptosis in neuron cells especially at high doses.