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Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma

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Abstract

Background

Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations.

Methods

We retrospectively reviewed paediatric (< 18 years) and adult patients (≥ 18 years) treated with salvage IT at two institutions. Haematologic toxicities were graded according to common terminology criteria of adverse events. Survival was estimated by the Kaplan–Meier method and compared by the Log Rank test.

Results

Fifty-three patients were treated with IT from Jan, 2010 to Dec, 2018 (n = 16 paediatric; n = 37 adult). IT was given as second-line (n = 34; 64%) or ≥ third-line (n = 19; 36%). There was no difference in ≥ grade 3/4 haematologic toxicity between paediatrics and adults (31% vs. 35% respectively; p = 0.76). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 12 (28%) stable disease and 19 (44%) disease progression. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.2 months, p = 0.039).

Conclusion

Irinotecan and temozolomide (IT) chemotherapy has activity for relapsed ES, with favourable toxicity and equally observed objective responses in the paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in future studies.

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References

  1. Burchill SA. Ewing's sarcoma: diagnostic, prognostic, and therapeutic implications of molecular abnormalities. J Clin Pathol. 2003;56(2):96–102.

    Article  CAS  Google Scholar 

  2. Potratz J, Dirksen U, Jürgens H, Craft A. Ewing sarcoma: clinical state-of-the-art. Pediatr Hematol Oncol. 2012;29(1):1–11.

    Article  CAS  Google Scholar 

  3. Grier HE, Krailo MD, Tarbell NJ, et al. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 2003;348(8):694–701.

    Article  CAS  Google Scholar 

  4. Womer RB, West DC, Krailo MD, et al. Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Childrenʼs Oncology Group. J Clin Oncol. 2012;30(33):4148–54. https://doi.org/10.1200/JCO.2011.41.5703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Juergens C, Weston C, Lewis I, et al. Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-EWING 99 clinical trial. Pediatr Blood Cancer. 2006;47(1):22–9. https://doi.org/10.1002/pbc.20820.

    Article  PubMed  Google Scholar 

  6. Brennan B, Kirton L, Marec-Berard P, et al. Comparison of two chemotherapy regimens in Ewing sarcoma (ES): Overall and subgroup results of the Euro Ewing 2012 randomized trial (EE2012). J Clin Oncol. 2020;38(15_suppl):11500. https://doi.org/10.1200/JCO.2020.38.15_suppl.11500.

    Article  Google Scholar 

  7. Ferrari S, Luksch R, Hall KS, et al. Post-relapse survival in patients with Ewing sarcoma. Pediatr Blood Cancer. 2015;62(6):994–9.

    Article  CAS  Google Scholar 

  8. Casey DA, Wexler LH, Merchant MS, et al. Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering experience. Pediatr Blood Cancer. 2009;53(6):1029–34.

    Article  Google Scholar 

  9. Leavey PJ, Mascarenhas L, Marina N, et al. Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence following multi-modality therapy: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2008;51(3):334–8.

    Article  Google Scholar 

  10. Cosetti M, Wexler LH, Calleja E, et al. Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience. J Pediatr Hematol Oncol. 2002;24(2):101–5.

    Article  Google Scholar 

  11. Bisogno G, Riccardi R, Ruggiero A, et al. Phase II study of a protracted irinotecan schedule in children with refractory or recurrent soft tissue sarcoma. Cancer. 2006;106(3):703–7.

    Article  CAS  Google Scholar 

  12. Wagner LM, McAllister N, Goldsby RE, et al. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr Blood Cancer. 2007;48(2):132–9.

    Article  Google Scholar 

  13. Kurucu N, Sari N, Ilhan IE. Irinotecan and temozolamide treatment for relapsed Ewing sarcoma: a single-center experience and review of the literature. Pediatr Hematol Oncol. 2015;32(1):50–9.

    Article  CAS  Google Scholar 

  14. Houghton PJ, Stewart CF, Cheshire PJ, et al. Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Clin Cancer Res. 2000;6(10):4110–8.

    CAS  PubMed  Google Scholar 

  15. Patel VJ, Elion GB, Houghton PJ, et al. Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Clin Cancer Res. 2000;6(10):4154–7.

    CAS  PubMed  Google Scholar 

  16. Huang M, Lucas K. Current therapeutic approaches in metastatic and recurrent Ewing sarcoma. Sarcoma. 2011;2011:863210.

    Article  Google Scholar 

  17. Palmerini E, Jones RL, Setola E, et al. Irinotecan and temozolomide in recurrent Ewing sarcoma: an analysis in 51 adult and pediatric patients. Acta Oncol. 2018;57(7):958–64.

    Article  CAS  Google Scholar 

  18. Farhat R, Raad R, Khoury NJ, et al. Cyclophosphamide and topotecan as first-line salvage therapy in patients with relapsed ewing sarcoma at a single institution. J Pediatr Hematol Oncol. 2013;35(5):356–60.

    Article  CAS  Google Scholar 

  19. Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer. 2006;47(6):795–800.

    Article  Google Scholar 

  20. Van Winkle P, Angiolillo A, Krailo M, et al. Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience. Pediatr Blood Cancer. 2005;44(4):338–47.

    Article  Google Scholar 

  21. Hernández-Marqués C, Lassaletta-Atienza A, Ruiz Hernández A, et al. Irinotecan plus temozolomide in refractory or relapsed pediatric solid tumors. An Pediatr (Barc). 2013;79(2):68–74.

    Article  Google Scholar 

  22. Blanchette PS, Lo A, Ng P, et al. Irinotecan and temozolomide in adults with recurrent sarcoma. J Solid Tumors. 2015;5(2):105–11.

    Article  Google Scholar 

  23. Gruber ML, Buster WP. Temozolomide in combination with irinotecan for treatment of recurrent malignant glioma. Am J Clin Oncol. 2004;27(1):33–8.

    Article  CAS  Google Scholar 

  24. Vredenburgh JJ, Desjardins A, Reardon DA, Friedman HS. Experience with irinotecan for the treatment of malignant glioma. Neuro Oncol. 2009;11(1):80–91. https://doi.org/10.1215/15228517-2008-075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Büyükkapu Bay S, Kebudi R, Görgün O, Zülfikar B, Darendeliler E, Çakır FB. Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: a single center experience. J Oncol Pharm Pract. 2019;25(6):1343–8. https://doi.org/10.1177/1078155218790798.

    Article  CAS  PubMed  Google Scholar 

  26. Mccabe MG, Moroz V, Khan M, et al. Results of the first interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma. J Clin Oncol. 2019;37(15 suppl):11007. https://doi.org/10.1200/JCO.2019.37.15_suppl.11007.

    Article  Google Scholar 

  27. McCabe MG, Kirton L, Khan M, et al. Results of the second interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). J Clin Oncol. 2020;38(15 suppl):11502. https://doi.org/10.1200/jco.2020.38.15_suppl.11502.

    Article  Google Scholar 

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Authors and Affiliations

  1. King Hussein Cancer Centre, Amman, Jordan

    S. Salah, O. Khozouz, T. Ismail, S. Yaser, A. Alnsour, O. Shahin, I. Sultan, R. Abuhijlih, H. Halalsheh & F. Abuhijla

  2. Peter MacCallum Cancer Centre, Melbourne, Australia

    Y. H. To & J. Lewin

  3. UT MD Anderson Cancer Centre, Huston, TX, USA

    O. Shahin

  4. ONTrac at Peter Mac Victorian Adolescent and Young Adult Cancer Service, Melbourne, Australia

    J. Lewin

  5. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia

    J. Lewin

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  1. S. Salah
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  4. T. Ismail
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  8. I. Sultan
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Correspondence to J. Lewin.

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Salah, S., To, Y.H., Khozouz, O. et al. Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma. Clin Transl Oncol 23, 757–763 (2021). https://doi.org/10.1007/s12094-020-02466-9

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  • DOI: https://doi.org/10.1007/s12094-020-02466-9

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