The effect of height on paclitaxel nerve damage.

Dying-back neuropathies result in sensory loss and motor signs in the distal distribution of the longest nerves of the body. It would be expected, therefore, that taller individuals with dying-back neuropathies would tend to have worse nerve damage than shorter individuals. This hypothesis was tested in patients receiving high dose paclitaxel. Nerve conductions and quantitative sensory tests were obtained in 21 breast cancer subjects, prior to and 20-40 days after 725 mg/m(2) paclitaxel administered intravenously over 24 h. Despite the uniform dose of paclitaxel, there was a wide variation in post minus pre-paclitaxel changes. Analysis by linear regression showed that decrease of peroneal nerve compound muscle action potential amplitude was significantly greater in taller subjects (P=0.004), and increase in cold detection threshold was greater in taller subjects (P=0.02). No correlation with height was found for paclitaxel drug clearance, maximum concentration, and area under the curve. Decrease in sural sensory nerve action potential amplitude and increase in vibration detection threshold did not correlate with height. In summary, the wide variation of changes seen in neurophysiological tests suggests that multiple factors are involved in determining the severity of neuropathy. Nerve length is probably one of these factors. To determine whether the effect of height is clinically important would require additional study with a larger number of subjects and longer clinical follow-up.

Neurophysiological study of peripheral neuropathy after high-dose Paclitaxel: lack of neuroprotective effect of amifostine.

PURPOSE: To determine if there is a beneficial effect of amifostine in preventing or reducing the neuropathy induced by high-dose paclitaxel. METHODS: Breast cancer patients receiving high-dose infusional paclitaxel (725 mg/m(2)/24 h) in combination with doxorubicin (165 mg/m(2)/96 h) and cyclophosphamide (100 mg/kg/2 h; ACT) were studied on two autologous peripheral blood stem cell transplant protocols, one with and one without amifostine (740 mg/m(2) administered over 10 min before and 12 h after initiation of the paclitaxel infusion). Patients were evaluated before ACT and 20-40 days later with neurological examination, a composite peripheral neuropathy score, peroneal and sural nerve conduction studies, and quantitative sensory testing. RESULTS: There was no significant difference in paclitaxel maximum concentration, systemic clearance, or area under the curve determinations. Narcotic requirement as well as recovery of hematopoietic counts were also similar in subjects with or without amifostine. After ACT was administered, there was a decrease in peroneal nerve compound muscle action potential amplitude and sural nerve sensory action potential amplitude, as well as an increase in vibratory and cold detection thresholds. Clinical composite peripheral neuropathy scores were similar despite amifostine treatment; and logarithm to the base 2 ratios post/pre ACT showed no significant effect of amifostine on peroneal nerve compound muscle action potential, sural nerve sensory action potential, vibratory detection thresholds, or cold detection thresholds. All subjects had acroparesthesias and lost their ankle deep-tendon reflexes after administration of ACT. CONCLUSIONS: Single high-dose paclitaxel produces predictable clinical and neurophysiological changes so that patients receiving high-dose therapy are ideal subjects to test the effectiveness of neuroprotective agents. Amifostine was ineffective in preventing or reducing the neurotoxicity of high-dose paclitaxel.