The assessment of neurologic toxicity was conducted differently among the studies as evident from the data reported in each individual study (see Tables 10to 16). Moreover, the frequency and severity of neurologic manifestations were influenced by prior and/or concomitant therapy with neurotoxic agents. 

In general, the frequency and severity of neurologic manifestations were dose-dependent in patients receiving single-agency paclitaxel. Peripheral neuropathy was observed in 60% of all patients (3% severe) and in 52% (2% severe) of the patients without pre-existing neuropathy. The frequency of peripheral neuropathy increased with cumulative dose. Paresthesia commonly occurs in the form of hyperesthesia. Neurologic symptoms were observed in 27% of the patients after the first course of treatment and in 34% to 51% from course 2 to 10. Peripheral neuropathy was the cause of paclitaxel discontinuation in 1% of all patients. Sensory symptoms have usually improved or resolved within several months of paclitaxel discontinuation. Pre-existing neuropathies resulting from prior therapies are not a contraindication for paclitaxel therapy.

In the Intergroup first-line ovarian carcinoma study (see Table 11), neurotoxicity included reports of neuromotor and neurosensory events. The regimen with paclitaxel 175 mg/m 2given by 3-hour infusion plus cisplatin 75 mg/m 2resulted in greater incidence and severity of neurotoxicity than the regimen containing cyclophosphamide and cisplatin, 87% (21% severe) versus 52% (2% severe), respectively. The duration of grade III or IV neurotoxicity cannot be determined with precision for the Intergroup study since the resolution dates of adverse events were not collected in the case report forms for this trial and complete follow-up documentation was available only in a minority of these patients. In the GOG first-line ovarian carcinoma study, neurotoxicity was reported as peripheral neuropathy. The regimen with paclitaxel 135 mg/m 2given by 24-hour infusion plus cisplatin 75 mg/m 2resulted in an incidence of neurotoxicity that was similar to the regimen containing cyclophosphamide plus cisplatin, 25% (3% severe) versus 20% (0% severe), respectively. Cross-study comparison of neurotoxicity in the Intergroup and GOG trials suggests that when paclitaxel is given in combination with cisplatin 75 mg/m 2, the incidence of severe neurotoxicity is more common at a paclitaxel dose of 175 mg/m 2given by 3-hour infusion (21%) than at a dose of 135 mg/m 2given by 24-hour infusion (3%). 

In patients with NSCLC, administration of paclitaxel followed by cisplatin resulted in a greater incidence of severe neurotoxicity compared to the incidence in patients with ovarian or breast cancer treated with single-agent paclitaxel. Severe neurosensory symptoms were noted in 13% of NSCLC patients receiving paclitaxel 135 mg/m 2by 24-hour infusion followed by cisplatin 75 mg/m 2and 8% of NSCLC patients receiving cisplatin/etoposide (see Table 15). 

Other than peripheral neuropathy, serious neurologic events following paclitaxel administration have been rare (<1%) and have included grand mal seizures, syncope, ataxia, and neuroencephalopathy.

Autonomic neuropathy resulting in paralytic ileus have been reported. Optic nerve and/or visual disturbances (scintillating scotomata) have also been reported, particularly in patients who have received higher doses than those recommended. These effects generally have been reversible. However, rare reports in the literature of abnormal visual evoked potentials in patients have suggested persistent optic nerve damage. Postmarketing reports of ototoxicity (hearing loss and tinnitus) have also been received.

Convulsions, dizziness, and headache have been reported.