970 An evaluation of the neurotoxicity of a phase I dose finding study of docetaxel (D) in combination with vinorelbin (V)

D, belonging to the taxoid class of anticancer agents, enhances microtubule assembly and inhibits the depolymerization of tubulin. The cytotoxic activity of V is through inhibition of the microtubule assembly. D and V have both shown clinical activity in advanced breast cancer as single agent. Additionally, therapeutic synergism has been observed in preclinical studies when the two drugs are combined simultaneously. Thus, a phase I study of a combination of these 2 drugs commenced in patients with metastatic breast cancer. However, as D. and V. induce mild neurotoxicity, neurological effects of this combination were evaluated. Neurological function at baseline, during (every 2 cycles and at the end of the study), and following treatment, in 13 metastatic breast cancer patients treated with docetaxel (60–85 mg/m2) and vinorelbine (20–22.5 mg/m2—D1–D5), none of them treated with vinca-alcaloids and/or CDDP, were prospectively evaluated. Deep tendon reflexes decrease was the most frequent abnormal finding, which occurred in 10 patients (77%). Mild, temporary and reversible grade 1 asymptomatic paresthesia were seen in 4 patients (31%). Pin sensibility, vibration sensation and muscular strength were always normal. Median and peroneal motor nerve conduction velocities, as well as median sensitive nerve conduction velocity, remained in the normal ranges. Peripheral neurotoxicity induced by the docetaxel-vinorelbine combination therapy appears to be mild (grade 1 according to NCI toxicity criteria).