Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors: A Children's Oncology Group study

Background Pemetrexed is a multi-targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile. Procedure Pemetrexed, at a dose of 1910?mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12, daily multivitamin supplementation, and dexamethasone. A two-stage design (10?+?10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem high-grade glioma. Results Seventy-two eligible subjects (39 males) were enrolled. Median age was 11 years (range 323). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 113). No complete or partial responses were observed. Stable disease, for a median of 5 (range 413) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n?=?1 each). Neutropenia (44%), anemia (35%), and elevated alanine transaminase (35%) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in =10% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%). Conclusions Pemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti-tumor activity in the childhood tumors studied. Pediatr Blood Cancer 2013;60:237241. (c) 2012 Wiley Periodicals, Inc.