Paclitaxel for the treatment of progressive or recurrent childhood brain tumors: A pediatric oncology phase II study

Purpose: To assess the efficacy and define the toxicity of paclitaxel given at 3 dosage of 350 mg/m(2) every 3 weeks as a 24-hour continuous infusion to children with recurrent or progressive primary brain tumors. Patients and Methods: Seventy-three eligible patients, ages 3 months to 19 years, with progressive or recurrent primary brain tumors were treated acco rding to a Pediatric Oncology Group (POG) phase II protocol with paclitaxel (POG 9330). Tumor histologic strata included: astrocytoma (n = 4), maligna nt glioma (n = 13), medulloblastoma (n = 16), brain stem glioma (n = 15). e pendymoma (n = 13), and miscellaneous histologies (n = 12). All patients ha d previous histologic confirmation of a primary intracranial or spinal cord tumor with magnetic resonance imaging or computed tomography documentation of unequivocally measurable progressive or recurrent disease. All patients had received previous therapy including surgery, radiation therapy, and/or chemotherapy, but no patient had been previously treated on more than one phase II trial. Paclitaxel was administered as a 24-hour intravenous infusi on at a dosage of 350 mg/m(2) every 3 weeks. Neurologic and neuroradiologic reevaluations were performed after every second course. Patients were allo wed to continue therapy for a total of 18 cycles in the absence of progress ive disease or unacceptable toxicity. Results: Seventy-five patients were enrolled onto the FOG 9330 protocol; tw o ineligible patients were removed from the study before receiving any ther apy. Of the 73 eligible patients, 72 were evaluable for toxicity and 70 wer e either fully or partially evaluable for disease response. There was one c omplete response and three partial responses (5.7%). Twenty patients had st able disease for more than 2 months. Toxicities included mild nausea, centr al nervous system toxicity, myelosuppression, and febrile neutropenia, incl uding one septic death. One grade 2 and two grade 3 allergic reactions occu rred. No cardiac toxicities or arthralgias were reported. Conclusion: Paclitaxel is well tolerated in children with recurrent or prog ressive brain tumors sit this dosage and schedule and may result in short-t erm disease stabilization in this: patient population. The lack of a signif icant number of patients with measurable: disease regression, however, prec ludes it from being identified as an active agent when administered as a si ngle agent by 24-hour continuous infusion.