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Systemic Treatment of Ewing Sarcoma: Current Options and Future Perspectives

Jose Duran Moreno
Jose Duran Moreno
, 
Georgios Papageorgiou
Georgios Papageorgiou
, 
Ioanna Gazouli
Ioanna Gazouli
 et 
Anastasios Kyriazoglou
Anastasios Kyriazoglou
   | 01 févr. 2022
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Article Category: Research Article
Publié en ligne: 01 févr. 2022
Pages: 3 - 27
Reçu: 13 juil. 2020
Accepté: 09 janv. 2021
DOI: https://doi.org/10.2478/fco-2021-0005
Mots clés
© 2021 Jose Duran Moreno et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Current treatment algorithm of localized Ewing's sarcoma. Note: VDC/IE = vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide; VAI = vincristine-actinomycin D-ifosfamide; VIDE = vincristine-ifosfamide-doxorubicin-etoposide; RT = radiotherapy; chemo = chemotherapy; BSC = best supportive care; MSI-h = microsatellite instability high; dMMR = deficient mismatch repair; PD = progressive disease.
Current treatment algorithm of localized Ewing's sarcoma. Note: VDC/IE = vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide; VAI = vincristine-actinomycin D-ifosfamide; VIDE = vincristine-ifosfamide-doxorubicin-etoposide; RT = radiotherapy; chemo = chemotherapy; BSC = best supportive care; MSI-h = microsatellite instability high; dMMR = deficient mismatch repair; PD = progressive disease.

Figure 2

Current treatment algorithm of metastatic Ewing's sarcoma. Note: VDC/IE = vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide; VAI = vincristine-actinomycin D-ifosfamide; VIDE = vincristine-ifosfamide-doxorubicin-etoposide; RT = radiotherapy; chemo = chemotherapy; BSC = best supportive care; MSI-h = microsatellite instability high; dMMR = deficient mismatch repair; WLI = whole lung irradiation; PR = partial response; CR = complete response; PD = progressive disease.
Current treatment algorithm of metastatic Ewing's sarcoma. Note: VDC/IE = vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide; VAI = vincristine-actinomycin D-ifosfamide; VIDE = vincristine-ifosfamide-doxorubicin-etoposide; RT = radiotherapy; chemo = chemotherapy; BSC = best supportive care; MSI-h = microsatellite instability high; dMMR = deficient mismatch repair; WLI = whole lung irradiation; PR = partial response; CR = complete response; PD = progressive disease.

Approved chemotherapeutic regimens against treatment of refractory/relapsed Ewing's sarcoma.

Regimens Cumulative patients ORR % PFS OS Main toxicities
Cyclophosphamide topotecan 49 32.6 N/A 61% at 1 year Myelotoxicity Alopecia
17 36 > 9.6 months N/A
13 23 8 months N/A
Window therapy 37 57 N/A N/A
Cyclophosphamide topotecan vincristine 14 50 N/A 15 months Myelotoxicity Alopecia
Irinotecan temozolomide 25 64 5.5 months N/A Myelotoxicity Diarrhea
+/− vincristine 14 28.5 5 months N/A
22 54 3 months 2 year OS: 26.9%55% at 25.7 months
19 63 8.3 months 55% at 1 year30.9% at 2 years
51 34 3.9 months 54.2% at 1 year13.9 months
15 40 6 months
20 55 5.5 months
118 20 4.7 months
Ifosfamide etoposide 17 94 N/A N/A Myelotoxicity, 97% Neutropenia
18 16 N/A 4.8 months
55 25 N/A N/A
High-dose ifosfamide 35 34 N/A 2-year OS: 29% Myelotoxicity Neurotoxicity Alopecia
30 N/A 4 year EFS: 27% 4-year OS: 39% Renal insufficiency
7 86 N/A N/A
Ifosfamide carboplatin etoposide 22 45 N/A 1 year: 43%2 years: 33% Myelotoxicity
Docetaxel gemcitabine 2 0 N/A N/A Myelotoxicity
2 0 N/A 4.5 months50% at 48 months Neurotoxicity Alopecia
6 67 10 months 13.7 months Allergic reactions
66 11.2 3 months

Agents under investigation in Phase I, II clinical trials, against Ewing's sarcoma.

Agent Target/mechanism of action Phase Eligibility Status
Eribulin Microtubule inhibitor II 12 months to 18 years old Recruiting
Eribulin–irinotecan Microtubule inhibitor - cytotoxic I–II 6 months to 17 years old Recruiting
Nab-paclitaxel–gemcitabine Microtubule inhibitor - cytotoxic II 12 to 30 years old Recruiting
I 6 months to 30 years old Recruiting
Nab-paclitaxel Microtubule inhibitor II 6 months to 80 years old Recruiting
Trabectedin–irinotecan Cytostatic–cytotoxic I 10 years and older Not yet recruiting
SM-88–MPS Protein synthesis, multiagent II 12 years and older Recruiting
Ganitumab–chemotherapy IGF-1R, cytotoxic/cytostatic III Up to 50 years old Active, not recruiting
Cabozantinib MET II 2 to 30 years old Recruiting
Palbociclib–temozolomide +/− irinotecan CDK4/6, multiagent I 2 to 20 years old Recruiting
Palbociclib–ganitumab CDK4/6, IGF-1R II 12 to 50 years old Recruiting
Pazopanib–irinotecan–temozolomide Multityrosine kinase inhibitor, multiagent I 6 to 30 years old Active, not recruiting
Olaparib–temozolomide +/− irinotecan PARP, multiagent I 16 years and older Recruiting
Niraparib–irinotecan–temozolomide PARP, multiagent I 13 years and older Recruiting
INCB059872 LSD-1 Ib 12 years and older Recruiting
Seclidemstat LSD-1 I 12 years and older Recruiting
Abemaciclib–temozolomide/irinotecan CDK4/6, multiagent I Up to 18 years old Recruiting
Selinexor–ixazomib CRM1, PSMB5 I 14 years and older Not yet recruiting
Vorinostat–chemotherapy Histone deacetylaces, multiagent I 1 to 30 years old Recruiting
Ivosidenib IDH-1 II 1 to 21 years old Not yet recruiting
Vigil–temozolomide–irinotecan Biological, multiagent III 2 years and older Active, not recruiting
CAR-T cells Biological I – II 18 to 65 years old Recruiting
EGFR806 CAR T cell immunotherapy Biological I 1 to 26 years old Recruiting
C7R-GD2.CART cells Biological I 1 to 74 years old Recruiting
pbi-shRNA™ EWS/FLI1 Type 1 LPX Biological I 8 years and older Active, not recruiting
CLR 131 Radioionated drug I 2 to 21 years old Recruiting
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