Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome
Introduction: In the multicenter, open-label, randomized, controlled, phase 3 trial RMS2005, maintenance chemotherapy (MC), defined as vinorelbine (VNL) and low-dose cyclophosphamide (CPM), has been tested in high-risk patients affected by Rhabdomyosarcoma (RMS). The trial's results have shown...
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Elsevier
2025-06-01
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| Series: | EJC Paediatric Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772610X2500008X |
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| author | Daniela Di Carlo Lisa Lyngsie Hjalgrim Beatrice Coppadoro Michela Casanova Andrea Ferrari Véronique Minard-Colin Hans Merks Gianni Bisogno |
| author_facet | Daniela Di Carlo Lisa Lyngsie Hjalgrim Beatrice Coppadoro Michela Casanova Andrea Ferrari Véronique Minard-Colin Hans Merks Gianni Bisogno |
| author_sort | Daniela Di Carlo |
| collection | DOAJ |
| description | Introduction: In the multicenter, open-label, randomized, controlled, phase 3 trial RMS2005, maintenance chemotherapy (MC), defined as vinorelbine (VNL) and low-dose cyclophosphamide (CPM), has been tested in high-risk patients affected by Rhabdomyosarcoma (RMS). The trial's results have shown that adding MC to 9 blocks of standard chemotherapy and surgery/radiotherapy improved overall survival. Following these results, MC has been incorporated into the standard of care for high-risk RMS patients. Drug doses were empirically titrated to avoid severe myelosuppression.Aspects like treatment adherence and drug doses effectively administered may have an important impact on the survival results and deserve to be studied. Methods: We analyzed 171 patients included in the RMS2005 protocol who received MC to quantify the deviation from the indications in terms of duration of maintenance and received doses and study its impact on survival. Results: Considering both drugs, 101/169 (60 %) of patients received a delivered cumulative dose (DCD) of at least 80 % of the planned cumulative dose, with a median DCD of 83 % (IQR 71–96).The median VNL and CPM relative dose intensity (RDI) was 0.88 (IQR 0.68–1).When the DCD or RDI for VNL, CPM and VNL plus CPM are included in the univariate and multivariate Cox model, as continuous or categorical variables, the effect is not significant both on the risk of developing events or death. Conclusion: The presented data about maintenance therapy suggested that dose modifications (as we registered them) did not affect event-free and overall survival. |
| format | Article |
| id | doaj-art-fed0b14ef7244418aab9907ff8d23d89 |
| institution | OA Journals |
| issn | 2772-610X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EJC Paediatric Oncology |
| spelling | doaj-art-fed0b14ef7244418aab9907ff8d23d892025-08-20T02:07:30ZengElsevierEJC Paediatric Oncology2772-610X2025-06-01510022110.1016/j.ejcped.2025.100221Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcomeDaniela Di Carlo0Lisa Lyngsie Hjalgrim1Beatrice Coppadoro2Michela Casanova3Andrea Ferrari4Véronique Minard-Colin5Hans Merks6Gianni Bisogno7Hematology Oncology Division, Department of Women’s and Childrn’s Health, University of Padova, Padova, Italy; Corresponding author.Department of Pediatrics and Adolescents Medicine, University Hospital Copenhagen, DenmarkHematology Oncology Division, Department of Women’s and Childrn’s Health, University of Padova, Padova, ItalyPediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyPediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, Milan, ItalyPediatric Oncology Unit, Institut Gustave Roussy, Paris, FrancePrincess Máxima Center for Pediatric Oncology, Utrecht, the NetherlandsHematology Oncology Division, Department of Women’s and Childrn’s Health, University of Padova, Padova, ItalyIntroduction: In the multicenter, open-label, randomized, controlled, phase 3 trial RMS2005, maintenance chemotherapy (MC), defined as vinorelbine (VNL) and low-dose cyclophosphamide (CPM), has been tested in high-risk patients affected by Rhabdomyosarcoma (RMS). The trial's results have shown that adding MC to 9 blocks of standard chemotherapy and surgery/radiotherapy improved overall survival. Following these results, MC has been incorporated into the standard of care for high-risk RMS patients. Drug doses were empirically titrated to avoid severe myelosuppression.Aspects like treatment adherence and drug doses effectively administered may have an important impact on the survival results and deserve to be studied. Methods: We analyzed 171 patients included in the RMS2005 protocol who received MC to quantify the deviation from the indications in terms of duration of maintenance and received doses and study its impact on survival. Results: Considering both drugs, 101/169 (60 %) of patients received a delivered cumulative dose (DCD) of at least 80 % of the planned cumulative dose, with a median DCD of 83 % (IQR 71–96).The median VNL and CPM relative dose intensity (RDI) was 0.88 (IQR 0.68–1).When the DCD or RDI for VNL, CPM and VNL plus CPM are included in the univariate and multivariate Cox model, as continuous or categorical variables, the effect is not significant both on the risk of developing events or death. Conclusion: The presented data about maintenance therapy suggested that dose modifications (as we registered them) did not affect event-free and overall survival.http://www.sciencedirect.com/science/article/pii/S2772610X2500008XMaintenance chemotherapyRhabdomyosarcomaChildrenCumulative doseRelative dose intensity |
| spellingShingle | Daniela Di Carlo Lisa Lyngsie Hjalgrim Beatrice Coppadoro Michela Casanova Andrea Ferrari Véronique Minard-Colin Hans Merks Gianni Bisogno Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome EJC Paediatric Oncology Maintenance chemotherapy Rhabdomyosarcoma Children Cumulative dose Relative dose intensity |
| title | Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome |
| title_full | Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome |
| title_fullStr | Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome |
| title_full_unstemmed | Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome |
| title_short | Maintenance therapy for pediatric patients with high-risk Rhabdomyosarcoma: A report of dose reductions and dose omissions on outcome |
| title_sort | maintenance therapy for pediatric patients with high risk rhabdomyosarcoma a report of dose reductions and dose omissions on outcome |
| topic | Maintenance chemotherapy Rhabdomyosarcoma Children Cumulative dose Relative dose intensity |
| url | http://www.sciencedirect.com/science/article/pii/S2772610X2500008X |
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