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dc.contributor.authorCasanova, M.
dc.contributor.authorBautista, F.
dc.contributor.authorCampbell-Hewson, Q.
dc.contributor.authorMakin, Guy W J
dc.contributor.authorMarshall, L. V.
dc.contributor.authorVerschuur, A.
dc.contributor.authorNieto, A. C.
dc.contributor.authorCorradini, N.
dc.contributor.authorPloeger, B.
dc.contributor.authorMueller, U.
dc.contributor.authorZebger-Gong, H.
dc.contributor.authorChung, J.
dc.contributor.authorGeoerger, B.
dc.date.accessioned2021-01-06T11:15:21Z
dc.date.available2021-01-06T11:15:21Z
dc.date.issued2020en
dc.identifier.citationCasanova M, Bautista F, Campbell-Hewson Q, Makin GWJ, Marshall LV, Verschuur A, et al. Phase 1 study of regorafenib in combination with vincristine and irinotecan in pediatric patients with recurrent or refractory solid tumors. Pediatric Blood & Cancer. 2020;67:S20-Sen
dc.identifier.urihttp://hdl.handle.net/10541/623614
dc.description.abstractBackground and Aims: This phase 1 study evaluated regorafenib plus vincristine/irinotecan in pediatric patients with rhabdomyosarcoma (RMS) and other solid tumors. Methods: Patients with relapsed/refractory tumors received intra- venous vincristine (1.5 mg/m 2 , Days 1,8) and irinotecan (50 mg/m 2 /day, Days1–5) plus once-daily oral regorafenib (6–<24 months: 60 mg/m 2 escalating to 65 mg/m 2 ;2–<18 years: 72 mg/m 2 escalating to 82 mg/m 2) on either Days 1–14 (concomitant dosing) or Days 8–21 (sequential dosing) during each 21-day cycle. Per protocol, 50% of patients had to have RMS. Results: Of 21 treated patients (RMS, n=12; Ewing sarcoma, n=5; neuroblastoma, n=3; Wilms tumor, n=1), 2 received concomitant (72 mg/m 2 ) and 19 sequential (72 mg/m 2 ,n=6; 82 mg/m 2 ,n=13) dos-ing. Median age was 10 years (1.5–17.0). Median number of cycles was 3 (1–17); irinotecan dose reductions occurred in 62%. Grade 3 dose-limiting toxicities were reported with concomitant (periph- eral neuropathy and liver injury [1]; pain, vomiting, febrile aplasia [1]) and sequential (rash and elevated aspartate aminotransferase [1]; thrombocytopenia [1]) dosing. Concomitant dosing was discontinued Maximum tolerated dose and recommended phase 2 dose (RP2D) of regorafenib in sequential combination was 82 mg/m 2 . Most com-mon grade 3 toxicities were neutropenia (71%), thrombocytope- nia (33%), leukopenia (29%), anemia (24%), and alanine aminotrans-ferase increased (24%). Response rate was 38%, including 1 complete (RMS) and 7 partial responses (5 RMS, 2 Ewing sarcoma); 3 had prior irinotecan. Of 12 patients with RMS, 6 (4 with alveolar subtype) had a response. Nine patients (43%) had stable disease (maximum 17 cycles). After the cut-off, 2 additional patients (1 RMS, 1 Ewing sarcoma) had a partial response. Conclusions: Regorafenib can be combined at its single-agent RP2D of 82 mg/m 2 with standard-dose vincristine/irinotecan (with appropri- ate dose modifications) in pediatric patients with refractory/relapsed solid tumors in a sequential dosing schedule. Activity was observed in patients with sarcomaen
dc.language.isoenen
dc.titlePhase 1 study of regorafenib in combination with vincristine and irinotecan in pediatric patients with recurrent or refractory solid tumorsen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentFondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Unit, Milano, Italy;en
dc.identifier.journalPediatric Blood & Canceren
dc.description.noteen]


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