Posted on Authorea 10 May 2021 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.162067454.46557337/v1 | This a preprint and has not been peer reviewed. Data may be preliminary. oi uo ohi eorf oe n patients and pediatric toxicity the model cardiac modest against xenograft the effectivity with in marrow, powerful camptothecin both bone and the tumor effect, on of side solid analogue effects non-hematologic semisynthetic side controllable is and myelosuppression, inhibitor, toxicity on I the topoisomerase to a kidney due Irinotecan, and patients liver of of types tumor function Wilms’ these impaired refractory but function, for or effective selected relapsed Wilms has be of radiotherapy, for treatment to targeted therapy the with standard for combined response a transient etoposide), as combination the carboplatin, used and the (cyclophosphamide, type, generally as CyCE refractory such are chemotherapy, or doxorubicin, and relapsed and/or therapy, the tumor vincristine and radiation with decades surgery, and nothing past Conventional actinomycin-D the done in of have dismal. tumor tumor advances still Wilms these renal as is diagnosed but childhood result children 85%, the 90% than for for over rate survival accounts exceed the tumor in improved embryonal greatly an been is tumor Wilms option alternative have an events provide adverse Introduction may fatal it No toxicity, tolerated etc. with the (38%), efficacy WT. and pain positive common R/R months), abdominal has most of control 0.5-12 (40%), treatment regimen with disease (range toxicity, leucopenia the AI months the for (62%), for The 3.5 assessable and alopecia was Conclusion: were PR) were survival patients events observed. 5 Sixteen progression-free 2 adverse been CR, median (PR), months). 4 (2 The 1-28 response or 50% (range SD). partial 3 months was 2 grade 5 8 rate and (CR), was response PR, to duration years) response 1 5 objective survival 11 complete received CR, median The to 2 patients (2 (0.5 (PD). These 64% years response: disease Sun was 4.2 disease. for progression of rate at refractory assessable 5 age with regimen were (SD), median patients patients AI with disease 2 response courses).14 patients with stable and observed 16 3 treated disease best of (median relapsed were the Total courses with as who Result: 8 patients defined WT evaluated. was 14 liposome was R/R response including hydrochloride toxicity The the enrolled, doxorubicin and were 2020. enrolled cycle and September two study irinotecan to last was present of 2018 the chemotherapy July combination The after salvage from the new Center Methods: of and Cancer WT. dismal University efficacy Yat-Sen was R/R the WT) evaluate for (R/R to (AI) tumor aimed Wilms regimen refractory study or This relapsed the needed. of prognosis The Purpose: Abstract 2021 10, May 4 3 2 1 Sun Huang Junting Zhang Lian Tumor Wilms Refractory or for Relapsed Liposome Hydrochloride Doxorubicin Plus Irinotecan it ffiitdHsia fGaghuMdclCollege University Medical Yet-Sen Guangzhou Sun of Hospital Affiliated CenterFifth Cancer University Yet-Sen CenterSun Cancer University Yat-sen Sun 4 3-6 h avg eie,sc steatraigcceo C iofmd,croltn tpsd)and etoposide) carboplatin, (ifosfamide, ICE of cycle alternating the as such regimes, salvage The . 1 unWang Juan , 2 uLiuhong Wu , 2 ayn Guo Lanying , 1 uqn Cai Ruiqing , 8-10 3 iQue Yi , 11-14 . 2 iu Zhen Zijun , 1 hs td fiioea npdarcpatients pediatric in irinotecan of study I phase A . 1 efiSun Feifei , 1 ihoZhang Yizhuo , 1 i Zhu Jia , 7 iie pin r remained are options Limited . 1,2 eia dacshave advances Medical . 2 uYn Lu Su-Ying , 1 n Xiaofei and , 1 , Posted on Authorea 10 May 2021 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.162067454.46557337/v1 | This a preprint and has not been peer reviewed. Data may be preliminary. yrclrd iooepu rntcnrgmnt h rgeso ftedsaeo h ieo h last the of time the or disease the of progression the Doxorubicin the to of start regimen the from irinotecan (SD) time stable Hydrochloride the plus (PR), as Doxorubicin response defined Liposome partial is of (CR), (PFS) Hydrochloride cycle Survival response Free Tumors) complete Progression one Solid (PD). of into: least progression Criteria divided and Evaluation is at (Response it after evaluation, RECIST efficacy the response for to standard According observed regimen. best irinotecan the plus Liposome as defined was Response group evaluation UFH toxicity were The and group mixed. Efficacy FH anaplasia. and and The focal predominant, protocol and group. COG blastemal anaplasia the (UFH) epithelial, diffuse to mesenchymal, histology included according unfavorable subtypes: was and four pathology group into Initial (FH) classified system. histology staging favorable COG into on classified based was stage Clinical all from obtained Pathology was given regimen. and consent AI be informed Stage for Written should treatment syndrome. atropine began choline (including before; prevent they pretreatment to when hour anti-allergic irinotecan patients an given before half hour be phenadryl) hydrochloride an should half doxorubicin or liposomes included diphenhydramine hydrochloride regimen dexamethasone, Doxorubicin AI cimetidine, cycles. weeks. 2 3 every every more refractory efficacy no or evaluated but (40mg/m relapsed withdrawal, were patient with liposome and or Patients toxicities courses, protocol. unacceptable 8 progression, NWTS-5 disease than the until to regimen according AI was received WT WT of treatment frontline Committee. The Ethics Center Cancer University Yat-Sen Schedule Sun Treatment the by approved was data. study clinical doxorubicin-containing This with Complete chemotherapy (4) received regimens. plus lesions; previously irinotecan Liposome had target or Hydrochloride who evaluable Patientsliposomes Doxorubicin Patients of (1) that (2) presence was years; following: criteria 18 The the Exclusion include (3) [?] criteria aged regimen; inclusion tumor chemotherapy The Wilms’ irinotecan refractory analysis. re- and Cancer who the University tumor relapsed in Yat-Sen Wilms’ with included Sun refractory at and and treated collected relapsed regimen were with irinotecan Center patients plus pediatric liposome hydrochloride 16 doxorubicin 2020, ceived September to 2018 July From with patients Patients of collection response describe a methods Doxorubicin we and in irinotecan- study, Materials regimens this from In hydrochloride benefited WT. doxorubicin refractory patients setting. or refractory was if irinotecan-liposomal relapsed or sarcoma that to relapsed unclear toxicity pediatric the still and for in is regimen alone Liposome it liposome Hydrochloride However, doxorubicin hydrochloride conventional of toxicity. doxorubicin toxicities hematologic of dose-limiting and ORR the liposomes reduce the 37.5% glycol-coated and that polyethylene efficacy showed in the encapsulated Research enhance doxorubicin to 79% of designed irinotecan- formulation was combined toxicitywas the novel (DAWT) tolerable (irinotecan that a showed tumor with regimen was efficacy, studies Wilms clinical liposome VI clinical positive anaplastic retrospective the have several diffuse of regimens nephroblastoma, containing diagnosed (ORR) refractory or newly rate relapsed for response the overall treated (WT) the vincristine) tumor including that daily with Wilms cancer, showed infusion solid relapsed pediatric Study iv. with of 60-min AREN0321 patients application a clinical of as the subset in administered a days reported was been study 21 has II bevacizumab) every phase temozolomide, days, in irinotecan 5 of for dose the that recommended 25 rntcnaddxrbcnhdohoielpsm a o ehooiiy adooiiy and cardiotoxicity, nephrotoxicity, low had liposome hydrochloride doxorubicin and Irinotecan . 2 e a,D)adiioea (50mg/m irinotecan and D1) day, per 15 rntcncmie ihohrceohrp gns(uha vincristine, as (such agents chemotherapy other with combined Irinotecan . 2 3,5,16-19 2 e a ih9-i nuin 15,repeated d1-5), infusion, 90-min with day per eut fteCide’ nooyGroup Oncology Children’s the of Results . 19,21-23 oouii hydrochloride Doxorubicin . 20 For . 24 . Posted on Authorea 10 May 2021 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.162067454.46557337/v1 | This a preprint and has not been peer reviewed. Data may be preliminary. ea oiiyhv enosre,admds des ffc a eamnsee totain service. outpatient and events at adverse administered fatal be No can effect 4). adverse (Table modest toxicities and the for observed, assessed been systemically have toxicity were and patients renal months), 3). 16 (ORR) table 0.5-12 rate of and (range response Total 1 months objective (Figure 3.5 the months) was 1-28 and survival (range SD), progression-free months 2 Toxicity 8 median and was The PR, duration 5 PR). survival CR, 5 median (2 the CR, 64% of (2 was last died 50% (DCR) at #11) was alive patient rate patients and #10, control two lung patient disease whole #9, #7 of The the patient patient Both follow-up. (patient#1, of PD, achieved patients last radiation follow-up. patients received four at without five last then other progression the alive and the at disease Of patients lesions months, disease follow-up. lung 3.7 3 Both of last the for regimen, at of follow-up died of therapy. AI remove disease patient died salvage to of after 1 but died performed other PR and were regimen regimen received reached AI chemotherapy disease then patients after salvage with SD and 5 further alive achieved to Of courses patient changed 6 achieved 1 follow-up. courses) CR after (patient#8) last disease, 3 achieved PD patient to at patients but 1 for (2 progression 4 regimen SD and disease tumor regimen), achieved AI radiation), of patients pulmonary AI of lung evidence two of of courses whole of radiation no courses received 4 and showing 6 surgery #14 after #12 follow-up, received to patient PR patient last 5 4 and patient# follow-up; at (received patients#13 and alive last PR #3 lesions, achieved and management(patients at including clinical patients regimen months chemotherapy further 5 salvage AI 28.8 courses after Of other of 6 for received after cycles months). disease CR then 8 9.2 with reached months, after alive who 5 CR 6 and months. after (Patient# achieved 32.4 cyclophosphamide, follow-up relapse 2). to (Table last and tumor 2.6 PD at showed topotecan from 5 alive SD, ranging regimen were Following 2 follow-up, AI CR PR, last (N=5). achieved of 5 at patients metastasis CR, alive two or and 2 were of site(N=2) site (50%) response: Both local patients local for at 14 of assessable progression of were both patients out either or 14 7 had (median, lung) regimen, Overall, patients months were this enrolled 12 sites of 16 courses metastasis to the several the 0.5 regimen, all was AI (N=9, PD of metastasis subsequent treatment the to to regimen Prior AI of treatment initial the 3.5months). from duration The the all Response of of 2 Histology courses) with 3 diagnosis. patients (median at 9 courses disease chemotherapy, 8 150/m bilateral with to had pretreated 1 patient received received 3 = patients one patients N with These and the II: 5), All group. (stage = FH to regimen. diagnosis tumor N as AI (0.5 between at classified IV: months) years was disease stage 108 advanced-stage diagnosis 4.2 6, to at had = of patients (7 patients N 17.5months age of 14 III: of median Most including stage time study, with refractory. 4, median this or disease, and in relapse disease refractory enrolled and refractory with were diagnosis or patients tumor relapsed 2 Wilms at years) and as 11 diagnosed disease 8:8) relapsed female, with (male: patients patients 16 of Total Kaplan-Meier and analysis, characteristics statistical Patient rate. for survival progression-free used and was rate survival IL) Result overall Chicago, calculate to (IBM, used 22.0 was version method software SPSS 4.03). (CTCAE The Hydrochloride Events Doxorubicin Adverse for the Criteria of Analysis Terminology start Common Statistical the the follow-up. on from last based time the is or assessment the Toxicity death as to defined regimen irinotecan is plus (OS) Liposome Survival Overall follow-up. 2 rd o400mg/m to rmr ie fperae hmteayrgmn h cuuaiedsso oouii were doxorubicin of doses accumulative The regimen. chemotherapy pretreated of lines more or 2 mda 250mg/m (median 2 Tbe1). (Table ) 3 nd iead5patients 5 and line Posted on Authorea 10 May 2021 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.162067454.46557337/v1 | This a preprint and has not been peer reviewed. Data may be preliminary. h epnet h Irgmncncnetdit uvvlbnfi;5P ainshdpo uvvl most strategy. survival, therapeutic poor new had a patients find PD to 5 needed benefit; and survival years into follow-up, patients 2 last converted PR within the 5 can died AI at of were regimen If survived out them AI radiotherapy) 4 WT. of or the chemotherapy; HR (surgery regimen to management AI as response clinical after the diagnosed further survival after longer was irinotecan- CR achieved the explored. patient achieved patients who further to CR the respectively. sensitive 2 be of study, 11.1%, to not this none and need was In (DA) WT study, 33.3% patients anaplasia HR was WT present patients for diffuse HR the effective WT relapsed 4 In is HR the including regimen and that type, regimens. IR indicate histological of salvage study ORR HR containing SIOP The in had of (BT). efficacy patients results type 9 The good blastemal showed and 5 VCR relapse, and with WT first combined were patients irinotecan patients better WT that 8 is DA showed liposome study treated hydrochloride clinical newly etc.). doxorubicin AREN0321 Bevacizumab, reason with TMZ, COG The combined VCR, The research. irinotecan as clinical (such of SIOP regimens of effect Irinotecan-containing that 21.4% curative for other than of the than effective better ORR is was that an tumor regimen be Wilms with AI may refractory tumor, the and regimens regimen Wilms relapsed irinotecan-containing that AI relapsed that with indicating after showed patients in study PR 50%, efficacy SIOP achieved was the poor 5 However, regimen and had tumor. AI CR Wilms’ achieved the refractory patients and of 2 relapsed ORR patients, evaluable the 14 and liposome the chemotherapy, hydrochloride among doxorubicin study, of this regimen In the accepted liposome we mg/m /m hydrochloride study 60 40mg doxorubicin this with was as of in patients combined dose refrac- liposome, pediatric Irinotecan tolerated and hydrochloride to maximum relapsed bicin weeks patients. the for 4 that WT chemotherapy every showed refractory rescue administered Study effective or anthra- tumor. an relapsed conventional Wilms become to the tory may liposome of liposome hydrochloride prognosis hydrochloride doxorubicin the doxorubicin relapsed the improve with Alternating relatively children may doxorubicin for to than cycline tumor. drug cardiotoxic chemotherapeutic exposed Wilms effective less refractory patients potentially and be a that become might showed may liposome Study liposome hydrochloride hydrochloride its doxorubicin doxorubicin. and that of liposome mg/m gests glycol-coated those 540–840 polyethylene doses, from in cumulative mg/m different encapsulated 250 high than doxorubicin markedly more of are no formulation were PK novel that studies a revealed SIOP mg/m is Studies and 400 COG liposome anthracyclines. with in of 5% tumor to dose Wilms 3% the with in restricted rate occurs effective have HF the anthracyclines doxorubicin-induced and of 21.4%, cardiotoxicity Irinotecan- of received the ORR who an about tumor had high Wilms ect.) notuniform enrolled not relapsed bevacizumab, of is was evaluable TMZ, number drugs VCR, with chemotherapy the a (including patients and studies, have regimens 14 retrospective irinotecan containing regimens that are of irinotecan-containing showed combination them study that of the retrospective shown most and have but small, tumor, is studies Wilms subject retrospective recurrent of in number effect certain a side years, and recent toxic In the of because chemotherapy delayed 11 Discussion patients are study, the fatigue, and this of mucositis chemotherapy. None In including and of symptoms, (13%) effects managed. nonspecific hepatic used. readily Several Modest and routinely observed. neutropenia. occurred, been febrile were or has myelosuppression medications toxicity (PEG-rhG-CSF) grade mild (7%) Factor Generally, antidiarrhea had cardiac Stimulating patients administered. alopecia the most Colony easily and (38%), Granulocyte if Injection was Human pain for manageable nausea Recombinant abdominal and was Pegylated vomiting (23%), received diarrhea 2 patients diarrhea to 4 were 1 or events Grade toxicity-related 3 (40%). 4 leucopenia or and 3 (62%), grade commonly The 2 23 o igedytreatment. day single 1 for nhaylnsaeeetv hmteaetc o ainswt im’tmr Concerns tumor. Wilms’ with patients for chemotherapeutics effective are Anthracyclines . 20 h IPciia td nold1 ainswt vlal efficacy, evaluable with patients 14 enrolled study clinical SIOP The . 2 i o aeeiec fauecnetv er alr,wihsug- which failure, heart congestive acute of evidence have not did , 4 227 Cmltv oe fdxrbcni patients in doxorubicin of doses .Cumulative 25 2 Acrigt u xeinei doxoru- in experience our to .According 23 h uaieeeto hssuyon study this of effect curative The . 220,28 Dxrbcnhydrochloride .Doxorubicin 19,21-23 29 Doxorubicin . 。 SIOP A Posted on Authorea 10 May 2021 | The copyright holder is the author/funder. All rights reserved. No reuse without permission. | https://doi.org/10.22541/au.162067454.46557337/v1 | This a preprint and has not been peer reviewed. Data may be preliminary. ainswt easdo ercoyNeuroblastoma. (2018). Refractory or 0432.CCR-18-1381 or relapsed Relapsed for with temozolomide G. Patients plus S. Irinotecan DuBois, K. 4 N. Cheung, & S. Modak, Oncology K., Kramer, neuroblastoma. H., refractory B. Kushner, 3 W. pliancy. developmental T. tumours. and D. genomics tumor Jones, solid 2 Pediatric A. M. Dyer, & A. 34 Pappo, X., Chen, 1 interest. Reference of conflicts no declare authors The statement Disclosure declare to Junting funding Lu, No Suying Zhu, manuscript. Jia the Sun, revised Feifei Juan Zhen Que, Acknowledgments Zhang, Zijun Yi Lian Cai, manuscript; study, Ruiqing the the Wu, designed drafted Liuhong Sun and Xiaofei Huang, analysis and Zhang the Yizhuo performed Guo, Wang Lanying Wang, Juan group Zhang, Lian FH for indicates especially liposome toxicities, hydrochloride tolerable Contributions with doxorubicin warranted. patients is and WT trial clinical irinotecan refractory Prospective or of WT. relapsed regimen for efficacy combination promising the the treatment continue the conclusion, could for effects experience In tumor. valuable adverse sample Wilms’ provided manageable limited study study refractory Furthermore, with this this or patients design. and relapsed because therapy, all non-randomized of of performed However, as delay be bias without study. regimen not selection this therapeutic could arise in may comparison some enrolled intervention, it acknowledge the were study, we group, routinely study, sizes this control Still, single-arm with In of therapy. a controllable agents. lack delayed As two easily is without these continued and existed. combine generally self-limited are to was regimen commonly limitations regimen therapeutic are therapeutic this effect doxorubicin this report adverse and explore. that to to the time suggesting worthy first noted is high, the we efficacy is not the this is improve note, further study Of can this liposome in hydrochloride hydrochloride doxorubicin delayed doxorubicin mucositis of patients of of dose toxicity the incidence dose-limiting (62%), of 40mg/m The the alopecia None liposome that including hydrochloride shown study mucositis. (16%). have this Mucositis is Studies in (23%), liposome observed toxicity. 2 diarrhea effects to than side (38%), due more 4 pain treatment cause time and relapsed prevent abdominal may 3 long to patients regimen (40%), factor grade AI stimulating time, most leucopenia common the granulocyte study, most follow-up long-acting that given The the concerning short were patients and In neutropenia. severe the all past, 8 suppression, had the cardiotoxicity. of marrow to patients in bone long-term Because chemotherapy the severe (1 high-intensity the of 3 received up none etc.). and (40-240 was follow but times arrhythmia, mg/m2 regimen to electrocardiogram, 120 failure, AI the needed was heart receiving in was liposome abnormalities as patients hydrochloride mild (such for doxorubicin had cardiotoxicity of courses patients dose treatment 7 cumulative of median mg/m2). number the median and the courses), study, this In 2751,di1.08oc21.7 (2015). doi:10.1038/onc.2014.474 5207-5215, , auerves Cancer reviews. Nature 24 2157,di1.20JO20.677 (2006). doi:10.1200/JCO.2006.06.7272 5271-5276, , tal. et tal. et hs ITilo lsri nCmiainwt rntcnadTmzlmd for Temozolomide and Irinotecan with Combination in Alisertib of Trial II Phase oeua hrceitc n hrpui unrblte cospeiti solid paediatric across vulnerabilities therapeutic and characteristics Molecular ora fciia nooy:oca ora fteAeia oit fClinical of Society American the of journal official : oncology clinical of Journal 2 19 ssf o easdadrfatr im tumor Wilms refractory and relapsed for safe is 2-3,di1.08s16-1-19x(2019). doi:10.1038/s41568-019-0169-x 420-438, , 5 lnCne Res Cancer Clin 24 1264,doi:10.1158/1078- 6142-6149, , 25 hte nraigthe increasing Whether . Oncogene Posted on Authorea 10 May 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162067454.46557337/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. hrp ucmso tg It VDsae eut fteCide’ nooyGopAREN0321 Group Oncology Children’s the of Results Disease: IV to II Stage of Outcomes C. tu- Therapy N. wilms relapsed Daw, multiply 20 of bevacizumab. Treatment and L. temozolomide Mascarenhas, (2014). irinotecan, doi:10.1002/pbc.24785 & vincristine, H. with M. mor Malogolowkin, R., Venkatramani, experience. 19 center single A (2019). tumors: doi:10.1177/1078155218790798 S. solid pediatric Bay, tory/relapsed Buyukkapu 18 sarcomas. tissue soft (2018). and 0107-9 bone refractory and M. recurrent M. Trucco, 17 tumors. solid with Y. Fujisaka, 16 the Res for Cancer irinotecan with Clin Experience S. S. Blaney, childhood. H. Friedman, 15 of & tumours A. solid glioma. D. to malignant Reardon, relation of A., treatment in Desjardins, treatment. J., pharmacology J. cellular Vredenburgh, and cancer 14 Clinical J. of G. Veal, reviews years treatment & Cancer J. 25 E. Estlin, 13 Irinotecan: C. (2019). doi:10.1016/j.phrs.2019.104398 Bailly, severity. 12 diarrhea irinotecan-induced N. (2019). doi:10.1016/j.pharmthera.2019.03.002 of A. biomarker Chamseddine, 11 Oncology Clinical of Oncology Society Cancer. Clinical Childhood American of the 9404. Survivors in Group of A. Oncology E. journal Feijen, Pediatric 10 official Trial Randomized : Group oncology (2016). Oncology doi:10.1200/JCO.2015.60.8851 clinical Children’s Lymphoma: of Non-Hodgkin the nal Lymphoblastic of Advanced-Stage or Report Leukemia A Lymphoblastic Acute T-Cell L. nosed B. study. Asselin, prospective 9 single-arm, 2, phase (2018). doi:10.1016/s1470-2045(18)30349-8 a 1239-1246, (AEROC): cancer ovarian refractory C.-Y. Lan, 8 report. Group Cancer Children’s a Update. tumor: M. An A. Tumor: Abu-Ghosh, Wilms 7 of Management Pharmacotherapeutic K. Pritchard-Jones, Drugs & Paediatr M. R. Oostveen, 6 Oncology Clinical of Society study. American consortium (2009). the therapy of neuroblastoma journal to official approach new a neuroblastoma: M. L. Wagner, 5 tal. et tal. et tal. et 21 tal. et tal. et tal. et tal. et 7 p lnOncol Clin J Jpn 33 23 (2001). 32-37 , -3 o:010/4220802- (2019). doi:10.1007/s40272-018-0323-z 1-13, , tal. et ptnbcmie ihoa tpsd nptet ihpaiu-eitn rplatinum- or platinum-resistant with patients in etoposide oral with combined Apatinib hs td fiioea npdarcptet:apdarcoclg ru study. group oncology pediatric a patients: pediatric in irinotecan of study I phase A hs lnclsuyo eyae iooa oouii JS0)i aaeepatients Japanese in (JNS002) doxorubicin liposomal pegylated of study clinical 1 Phase tal. et 7438,di1.20JO21.158 (2015). doi:10.1200/JCO.2015.61.5187 3774-3780, , qiaec ai o anrbcnt oouii nRlto oLt er Failure Heart Late to Relation in Doxorubicin to Daunorubicin for Ratio Equivalence hs ra foa rntcnadtmzlmd o hlrnwt easdhigh-risk relapsed with children for temozolomide and irinotecan oral of trial I Phase adortcinadSft fDxaoaei ainsTetdfrNwyDiag- Newly for Treated Patients in Dexrazoxane of Safety and Cardioprotection ciiyo icitn n rntcni iueAalsi im uo and Tumor Wilms Anaplastic Diffuse in Irinotecan and Vincristine of Activity 29 hs Isuyo esrlmsadlpsmldxrbcnfrptet with patients for doxorubicin liposomal and temsirolimus of study II phase A fsaie abpai n tpsd ncide ihpo-ikrlpe Wilms’ relapsed poor-risk with children in etoposide and carboplatin Ifosfamide, tal. et tal. et 5-7,di1.06s3577(20193(2003). doi:10.1016/s0305-7372(02)00109-3 253-273, , Neuro-oncology ora fciia nooy:oca ora fteAeia oit of Society American the of journal official : oncology clinical of Journal 36 icitn,iioea,adtmzlmd ramn o refrac- for treatment temozolomide and irinotecan, Vincristine, 6-7,di1.03jc/y19(2006). doi:10.1093/jjco/hyl109 768-774, , netnlbacterial Intestinal n Oncol Ann 11 09,di1.251281-0805(2009). doi:10.1215/15228517-2008-075 80-91, , 6 13 lnSroaRes Sarcoma Clin 6-6,di1.03ann/d08(2002). doi:10.1093/annonc/mdf028 460-469, , hraooy&therapeutics & Pharmacology 27 β- hraooia research Pharmacological 2019,doi:10.1200/JCO.2008.18.5918 1290-1296, , lcrnds sapsil predictive possible a as glucuronidase eiti lo cancer & blood Pediatric no hr Pract Pharm Oncol J 8 1 doi:10.1186/s13569-018- 21, , ora fciia nooy: oncology clinical of Journal h actOncology Lancet The 148 25 34 199 61 1343-1348, , 854-862, , 104398, , 756-759, , 1-15, , Jour- 19 , Posted on Authorea 10 May 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162067454.46557337/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. ihecc seset(n=14) assessment efficacy with 1 Figure legend Figure D. against medicine D. Protecting Hoff, E. Von 29 S. Lipshultz, protocol. & 2016 SIOP-RTSG H. M. UMBRELLA E. M. Heuvel-Eibrink, Herman, den van L., 28 strategies. promising T. most Miller, the (2005). of C., doi:10.1111/j.1365-2141.2005.05759.x review 561-578, L. a Kremer, damage: myocardial A., anthracycline-induced K. Wouters, 27 childhood. of tumors renal of M. Vujani´c, G. 26 results. preliminary A. Munoz, 25 liposomes. coated polyethylene-glycol Group. in Study encapsulated Tumor doxorubicin A. Renal Gabizon, SIOP 24 the from report (2018). literature-A doi:10.1002/pbc.26849 the of A. view J. Hol, 23 Oncology study. Clinical Group of Society Oncology American Children’s a neuroblastoma: R. Bagatell, 22 21 (2020). doi:10.1200/JCO.19.01265 1568, Study. < hs td fIioea nPdarcPatients.pdf Pediatric in Irinotecan of Study I Phase A ora fciia nooy:oca ora fteAeia oit fCiia Oncology Clinical of Society American the of journal official : oncology clinical of Journal 91 . alnMirgahfrporsinfe uvvladoealsria npatients in survival overall and survival progression-free for graph Kaplan-Meier 1-1,di1.3600-899--1 (1979). doi:10.7326/0003-4819-91-5-710 710-717, , tal. et tal. et tal. et tal. et tal. et eiti lo cancer & blood Pediatric eyae iooa oouii yrclrd PD o dacdsroa nchildren: in sarcomas advanced for (PLD) hydrochloride doxorubicin liposomal Pegylated tal. et rntcnfrrlpe im uo npdarcptet:SO xeineadre- and experience SIOP patients: pediatric in tumor Wilms relapsed for Irinotecan hs Isuyo rntcnadtmzlmd ncide ihrlpe rrefractory or relapsed with children in temozolomide and irinotecan of study II Phase rlne iclto ieadehne cuuaini ainn xdtsof exudates malignant in accumulation enhanced and time circulation Prolonged eie nentoa oit fPeiti nooy(IP okn classification working (SIOP) Oncology Paediatric of Society International Revised ikfcosfrdxrbcnidcdcnetv er failure. heart congestive doxorubicin-induced for factors Risk eia n eiti oncology pediatric and Medical tal. et 29 oiinppr ainl o h ramn fWlstmu nthe in tumour Wilms of treatment the for Rationale paper: Position a e Urol Rev Nat 0-1,di1.20JO21.170 (2011). doi:10.1200/JCO.2010.31.7107 208-213, , 43 5-5,di1.02pc209(2004). doi:10.1002/pbc.20029 152-155, , 7 ora fciia nooy:oca ora fthe of journal official : oncology clinical of Journal 14 4-5,di1.08nuo.0713(2017). doi:10.1038/nrurol.2017.163 743-752, , > 38 . 98,di1.02mo17 (2002). doi:10.1002/mpo.1276 79-82, , acrRes Cancer 54 eit lo Cancer Blood Pediatr 8-9 (1994). 987-992 , rJHaematol J Br naso internal of Annals 38 1558- , 131 65 , , Posted on Authorea 10 May 2021 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.162067454.46557337/v1 — This a preprint and has not been peer reviewed. Data may be preliminary. doxorubicin-hydrochloride-liposome-for-relapsed-or-refractory-wilms-tumor Table.pdf file Hosted vial at available https://authorea.com/users/413051/articles/521506-irinotecan-plus- 8