PACLITAXEL (TAXOL) INDUCES CUMULATIVE MILD NEUROTOXICITY

Paclitaxel (Taxol), a new antineoplastic drug, has been reported to be neurotoxic at doses above 200 mg/m(2) per course. It is uncertain whe ther neurotoxicity is related to cumulative amounts of paclitaxel. Neu ropathy was prospectively assessed in 18 patients with breast cancer, receiving between two and eight courses of 135 or 175 mg/m(2) of pacli taxel. Vibratory perception thresholds (VPT) and tendon reflex scores were proportionally related to the corresponding cumulative amounts of paclitaxel (P = 0.002; P = 0.0003). The amounts of paclitaxel adminis tered between the first and last assessments (175-1225 mg/m(2)) were r elated to concomitant changes in WT (P = 0.034), Paclitaxel had no cle ar neurotoxic threshold; if present, it lies below 540 mg/m(2), Rather , VPT appeared to increase 0.1 mu m per 400 mg/m(2) over the entire ra nge of 175-1225 mg/m(2) of paclitaxel. Clinical neuropathy prevailed i n 0/8 patients at screening and in 5/10 patients at the final assessme nt (P = 0.029). Neuropathy never exceeded grade 1. Thus, although neur otoxicity of paclitaxel is frequent and cumulative, it remains mild or subclinical up to at least 1400 mg/m(2) administered over eight cycle s.