Late toxicity comparison of alkylating-based maintenance regimen with cyclophosphamide (VAC) versus ifosfamide (VAI) in Ewing sarcoma survivors treated in the randomized clinical trial Euro-EWING99-R1 in France.
Fiche publication
Date publication
octobre 2022
Journal
International journal of cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ENTZ-WERLE Natacha
Tous les auteurs :
Corvest V, Marec-Bérard P, Lervat C, Pacquement H, Toulmonde M, Gentet JC, Laurence V, Cleirec M, Mansuy L, Bompas E, Castex MP, Taque S, Filhon B, Tabone MD, Verité C, Entz-Werle N, Saumet L, Guimard G, Pondrom M, Chevreau C, Flandrin J, Duranteau L, Rousset-Jablonski C, Brugières L, Jimenez M, Le Deley MC, Gaspar N, Fresneau B
Lien Pubmed
Résumé
In Euro-EWING99-R1 randomized trial, cyclophosphamide was shown to be non-inferior to ifosfamide in consolidation of standard-risk Ewing sarcoma (SR-EWS) after a common induction with VIDE (vincristine-ifosfamide-doxorubicin-etoposide). We present the results of the late effects analysis of VAC (vincristine-dactinomycin-cyclophoshamide) vs VAI (vincristine-dactinomycin-ifosfamide) conducted in Euro-EWING99-R1 French cohort. Of 267 French randomized patients, 204 were alive and free-of-relapse at 5-years including 172 with available long-term follow-up data concerning cardiac, renal and/or gonadal functions (sex-ratio M/F=1.3, median age at diagnosis=14years): 84 randomized in VAC (median cumulative doses: cyclophosphamide=9.7g/m , ifosfamide=59.4g/m ) and 88 in VAI (ifosfamide=97.1g/m ). With a median follow-up of 10 years (range=5-17), five late relapses and five second malignancies were recorded. The 10-year event-free survival among 5-year free-of-relapse survivors was similar between VAC and VAI (93% vs 95%, p=0.63). We estimated the 10-year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95%CI=1.1-7.6%) and 34.8% (95%CI=26.8-42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, p=0.02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, p<0.01). At 10 years, gonadal toxicity was observed in 27% and 28% of pubertal men and women, respectively, without significant difference between VAC and VAI. Kidney and gonadal toxicities represent major issues in Euro-EWING99-R1, with significantly higher risk of kidney toxicities with VAI, without significant gonadal toxicity reduction. These results support the need to limit cumulative doses of both alkylating agents and to use mixed regimen as in VIDE-VAC or VDC/IE (vincristine-doxorubicin-cyclophoshamide/ifosfamide-etoposide). This article is protected by copyright. All rights reserved.
Mots clés
Antineoplastic Combined Chemotherapy Protocols/adverse effects, Child, Cyclophosphamide/ adverse effects, Ewing/drug therapy, Ifosfamide/ adverse effects
Référence
Int J Cancer. 2022 10 17;: