Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing

Background. Paclitaxel-induced peripheral neuropathy (PN) may be severe and dose-limiting at initial doses greater than or equal to 275 mg/M-2, but its neurotoxicity at doses less than or equal to 250 mg/M-2 has been incompletely characterized. The purposes of this study were to characterize and quantify paclitaxel-induced PN and to determine the utility of quantitative sensory testing (QST). Methods. We prospectively examined clinically and by QST 37 women with metastatic breast cancer, treated with paclitaxel (200-250 mg/m2) (average number of cycles = 7.3 over an average of 20.1 weeks). QST included thermal threshold (TT) and vibration threshold (VT). Results. Paresthesias appeared in 31 (84%) patients after an average of 1.7 cycles and an average cumulative dose of 371.5 mg/M-2. Symptoms occurred after the first or second dose in 26 (84%) patients and then stabilized in 10 (32%), improved in 13 (42%) despite continued treatment, resolved completely in 6 (19%), and were progressive in 2 (7%). Paclitaxel was discontinued in only (3%) patient because of neurotoxicity and no patient required dose reduction because of PN. Thirty-six (97%) developed signs of PN. The most sensitive QST was great toe VT but QST did not predict or identify subclinical PN in any patient. Neurologic syndromes other than PN developed in 12 (32%) patients, and 7 were due to metastatic cancer. Conclusions. 1) Paclitaxel-induced PN is mostly sensory, and begins after the first or second dose. At these doses the neuropathy is mild, and rarely dose-limiting. 2) QST quantified the neuropathy but was less sensitive than the clinical examination. 3) Knowledge of the features of paclitaxel's PN allows it to be differentiated from other neurologic syndromes which may signal tumor progression.