{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:27:55Z","timestamp":1778221675584,"version":"3.51.4"},"reference-count":13,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Irinotecan is a drug active against pediatric sarcomas with a toxicity profile that theoretically allows for its association with more myelotoxic drugs. We examined the feasibility of a dose\u2010density strategy integrating irinotecan in standard chemotherapy regimens for patients with high\u2010risk sarcomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Between November 2013 and January 2020, 23 patients \u226425\u00a0years old were included in the study. Eleven patients newly diagnosed with metastatic disease received nine cycles of IrIVA (irinotecan\u2010ifosfamide\u2010vincristine\u2010actinomycin D; ifosfamide 3\u00a0g\/m<jats:sup>2<\/jats:sup> on days 1 and 2, vincristine 1.5\u00a0mg\/m<jats:sup>2<\/jats:sup> on day 1, actinomycin D 1.5\u00a0mg\/m<jats:sup>2<\/jats:sup> on day 1, irinotecan 20\u00a0mg\/m<jats:sup>2<\/jats:sup> for 5 consecutive days starting on day 8) as first\u2010line therapy. Two relapsed patients received IrIVA and 10 IrVAC (irinotecan\u2010vincristine\u2010actinomycin D\u2010cyclophosphamide; cyclophosphamide 1.5\u00a0g\/m<jats:sup>2<\/jats:sup> on day 1 instead of ifosfamide). Feasibility was assessed in terms of toxicity and time to complete the treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventeen rhabdomyosarcomas, four Ewing sarcomas, two desmoplastic small round cell tumors received a total of 181 cycles (range 2\u201310). Grade 4 neutropenia occurred in 62.4% of the cycles. Thirteen patients had febrile neutropenia. Diarrhea occurred in 14 cycles. The median time to complete the treatment was 195\u00a0days (range 170\u2013231), 83.4% of cycles were administered on time or with a delay &lt;1\u00a0week. With a median follow\u2010up of 2.6\u00a0years (range 0.2\u20135.0), 12 patients are alive, nine complete remissions, three with the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A dose\u2010density strategy combining irinotecan with standard chemotherapy is feasible. This approach will be investigated in the next trial coordinated by the European pediatric Soft tissue sarcoma Study Group.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28951","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T06:54:27Z","timestamp":1615445667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Integrating irinotecan in standard chemotherapy: A novel dose\u2010density combination for high\u2010risk pediatric sarcomas"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4462-5523","authenticated-orcid":false,"given":"Gianni","family":"Bisogno","sequence":"first","affiliation":[{"name":"Maternal and Child Health Department Padua University Hospital  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4724-0517","authenticated-orcid":false,"given":"Andrea","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Unit Fondazione IRCCS Istituto Nazionale Tumori  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Tagarelli","sequence":"additional","affiliation":[{"name":"Pediatric Hematology, Oncology and Stem Cell Transplant Division Padua University Hospital  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Sorbara","sequence":"additional","affiliation":[{"name":"Pediatric Hematology, Oncology and Stem Cell Transplant Division Padua University Hospital  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Chiaravalli","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Unit Fondazione IRCCS Istituto Nazionale Tumori  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Poli","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Department Padua University Hospital  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Scarzello","sequence":"additional","affiliation":[{"name":"Radiotherapy Division Istituto Oncologico Veneto  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"De Corti","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Unit, Department of Women's and Children's Health Padua University Hospital  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Casanova","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Unit Fondazione IRCCS Istituto Nazionale Tumori  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1680-0240","authenticated-orcid":false,"given":"Maria Carmen","family":"Affinita","sequence":"additional","affiliation":[{"name":"Pediatric Hematology, Oncology and Stem Cell Transplant Division Padua University Hospital  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.7207"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300891618792479"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2019.04.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.06.015"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00613"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.41.5703"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.4048"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13569-015-0035-x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20928"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30337-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.77.9694"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24621"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25837"}],"container-title":["Pediatric Blood &amp; 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