Folate, antifolates, and folate analogs in Pediatric Oncology

Hum, Martina; Kamen, Barton A.

doi:10.1007/bf00173686

Cited by 8 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Folate antagonists have been used in the treatment of childhood cancers since the 1940s when aminopterin was introduced; its use was superseded by methotrexate, an antifol with a better therapeutic index and a more reliable level/dose relationship [8].…”

Section: Introductionmentioning

confidence: 99%

“…Fluorouracil is another antifol currently used in pediatric cancer for treatment of hepatoblastoma and nasopharyngeal carcinoma. Resistance to the antifols currently used in the clinic, occurring as a result of alterations in folate transport as well as up-regulation of DHFR or down-regulation of folylpolyglutamate synthetase, has led to the development of new antifols such as edatrexate, raltitrexed, trimetrexate, as well as pemetrexed [8].…”

Section: Introductionmentioning

confidence: 99%

“…Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range [1][2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Warwick

Malempati

Krailo

et al. 2012

Pediatric Blood & Cancer

View full text Add to dashboard Cite

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 3–23). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 1–13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4–13) cycles, was observed in 5 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.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%