One-hour paclitaxel via weekly infusion: dose-density with enhanced therapeutic index.
A preliminary report of phase II trial of paclitaxel (Taxol) administered in a dose-dense manner as first- and second-line therapy for metastatic breast cancer is presented. Patients who had received one or two prior chemotherapy regimens for metastatic disease or in the adjuvant setting were eligible. Prior treatment with an anthracycline was permitted, but patients who had previously received taxanes were excluded. Initial dose was paclitaxel 100 mg/m2 infused over 1 hour weekly until disease progression or intolerable toxicity. To date, significant activity and a highly favorable toxicity profile have been observed with 1-hour paclitaxel < or = 100 mg/m2. Less myelosuppression occurred than would have been expected with a standard regimen (paclitaxel 175 mg/m2 given over 3 hours q3wks). Neurotoxicity became dose limiting at paclitaxel > 100 mg/m2/wk. The apparent safety and high therapeutic index of paclitaxel administered in a dose-dense fashion increases therapeutic options for patients with breast cancer, and further studies are warranted.