{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:16:00Z","timestamp":1791123360197,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:00:00Z","timestamp":1340841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Eli Lilly and Company, and National Cancer Institute","award":["U10 CA98543"],"award-info":[{"award-number":["U10 CA98543"]}]},{"name":"Eli Lilly and Company, and National Cancer Institute","award":["U10 CA98413"],"award-info":[{"award-number":["U10 CA98413"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pemetrexed is a multi\u2010targeted 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>\n                      Pemetrexed, at a dose of 1910\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , was administered as a 10\u2010minute intravenous infusion every 21 days. Patients also received vitamin B\n                      <jats:sub>12<\/jats:sub>\n                      , daily multivitamin supplementation, and dexamethasone. A two\u2010stage design (10\u2009+\u200910) 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\u2010brainstem high\u2010grade glioma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy\u2010two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3\u201323). Sixty\u2010eight were evaluable for response. The median number of cycles administered was 2 (range 1\u201313). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4\u201313) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n\u2009=\u20091 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 \u226510% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2010tumor activity in the childhood tumors studied. Pediatr Blood Cancer 2013;60:237\u2013241. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.24244","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T11:37:38Z","timestamp":1340883458000},"page":"237-241","source":"Crossref","is-referenced-by-count":37,"title":["Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors: A Children's Oncology Group study"],"prefix":"10.1002","volume":"60","author":[{"given":"Anne B.","family":"Warwick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Malempati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Krailo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Melemed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Gorlick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Ames","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Safgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Adamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Blaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,6,28]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.2.1.13"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11279"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.9-5-482"},{"key":"e_1_2_5_5_2","first-page":"1116","article-title":"Ly231514, a pyrrolo[2,3\u2010d]pyrimidine\u2010based antifolate that inhibits multiple folate\u2010requiring enzymes","volume":"57","author":"Shih C","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_5_6_2","first-page":"42","article-title":"Enzyme inhibition, polyglutamation, and the effect of LY 231514 (MTA) on purine biosynthesis","volume":"26","author":"Mendelsohn LG","year":"1999","journal-title":"Semin Oncol"},{"key":"e_1_2_5_7_2","first-page":"437","article-title":"Role of thymidylate synthase in the antitumor activity of the multitargeted antifolate, LY231514","volume":"19","author":"Schultz RM","year":"1999","journal-title":"Anticancer Res"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2571(97)00017-4"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00173686"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(03)01260-9"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.11.001"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510624200"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00200-5"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.1694"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"e_1_2_5_16_2","unstructured":"CTEP.Common terminology criteria for adverse events. 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