Shorter Paclitaxel Infusions Add to Neuropathy Risk

NEW ORLEANS--In combination with cisplatin (Platinol) for treatmentof gynecologic malignancies, 3-hour infu-sional paclitaxel (Taxol)might be easier to administer but it produces more peripheralneuropathy than the standard 24-hour infusion, a Cleveland Clinicstudy shows.

"The incidence of neurological side effects is excessive,"Maurie Markman, MD, reported at the Society of Gynecologic Oncologistsmeeting. "This is likely the result of high peak concentrationsof two neurotoxic agents reaching the peripheral nerves at thesame time. We recommend against its use."

The study examined 38 patients with ovarian, primary peritoneal,and endometrial malignancies, who received cis-platin (75 mg/m²)and a 3-hour infusion of paclitaxel (135 or 175 mg/m²). Therapyhad to be modified in 42% of patients.

The regimen was quite active, producing a 90% reduction in CA125 levels over pretreatment levels in 23 patients (70%). However,27 patients (71%) developed neurological toxicity, which was severein several cases. Sixteen patients (42%) experienced grade 2 orgreater peripheral neuropathy; 21% of these had grade 3 or 4 neuropathy.

In contrast, patients receiving pacli-taxel over 24 hours andthe same dose of cisplatin in the Gynecologic Oncology Group ovariancancer protocol had only a 13% incidence of grade 2 or greaterperipheral neuropathy, said William McGuire III, MD, of EmoryUniversity. "The message is that changing the schedule ofadministration significantly changes the toxicity," he said.