Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report

Hernando‑Cubero,Jorge; Sanz‑Moncasi,Pilar; Hernández‑García,Alba; Pajares‑Bernard,Isabel; Martínez‑Trufero,Javier

doi:10.3892/ol.2016.4950

Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report

Authors:
- Jorge Hernando‑Cubero
- Pilar Sanz‑Moncasi
- Alba Hernández‑García
- Isabel Pajares‑Bernard
- Javier Martínez‑Trufero
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Affiliations: Department of Medical Oncology and Pathology, University Hospital Miguel Servet, 50008 Zaragoza, Spain
Published online on: August 3, 2016 https://doi.org/10.3892/ol.2016.4950
Pages: 2936-2941
Copyright: © Hernando‑Cubero et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Ewing's sarcoma family of tumors (ESFT) comprises a number of rare malignant tumors. Standard first‑line treatment for patients with these tumors includes chemotherapy with a five‑drug regimen of vincristine, doxorubicin (Adriamycin®) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). In cases of inadequate response, there are a number of second‑line regimens available. However, further treatment options are required for those patients with disease unresponsive to standard treatment. Trabectedin is a novel treatment option for patients with ESFT. The present study reports the case of a Caucasian 69‑year‑old female patient who presented with a soft tissue mass on the chest wall that had developed 7 months earlier. A computed tomography scan revealed a 9x8x7‑cm mass on the anterior chest wall above the pectoral muscle. Histopathological evaluations and molecular analysis indicated that it was consistent with a metastatic extraskeletal Ewing's sarcoma. The patient was treated with an alternating VAC/IE regimen; however, an inadequate response was observed. The patient received second‑line treatment with a gemcitabine and dacarbazine combination regimen, but the disease progressed. Subsequently, treatment with trabectedin (1.5 mg/m2 as a 24‑h continuous infusion every 3 weeks) was initiated. Trabectedin treatment resulted in long‑lasting (18 months) progression‑free survival. It is vital that novel drugs continue to being developed for patients with ESFT following progression subsequent to standard chemotherapy. The current report presents a case of a patient with metastatic, pre‑treated Ewing's sarcoma achieving disease stabilization with trabectedin. Based on these results and the observed tolerability profile, trabectedin represents an alternative treatment for patients with ESFT. Further studies are required in order to determine the efficacy of trabectedin as monotherapy or in combination with other drugs. It is also important to identify which tumor subtypes, specific translocations and patient profiles will benefit the most from treatment with trabectedin.

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1	Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, Ambros PF, Sheer D, TurcCarel C, Triche TJ, et al: The Ewing family of tumors-a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 331:294–299. 1994. View Article : Google Scholar : PubMed/NCBI
2	Ng TL, O'Sullivan MJ, Pallen CJ, Hayes M, Clarkson PW, Winstanley M, Sorensen PH, Nielsen TO and Horsman DE: Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn. 9:459–463. 2007. View Article : Google Scholar : PubMed/NCBI
3	Urano F, Umezawa A, Yabe H, Hong W, Yoshida K, Fujinaga K and Hata J: Molecular analysis of Ewing's sarcoma: Another fusion gene, EWS-E1AF, available for diagnosis. Jpn J Cancer Res. 89:703–711. 1998. View Article : Google Scholar : PubMed/NCBI
4	Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, et al: Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 348:694–701. 2003. View Article : Google Scholar : PubMed/NCBI
5	Mora J, Cruz CO, Parareda A and de Torres C: Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. J Pediatr Hematol Oncol. 31:723–729. 2009. View Article : Google Scholar : PubMed/NCBI
6	Rapkin L, Qayed M, Brill P, Martin M, Clark D, George BA, Olson TA, WasilewskiMasker K, Alazraki A and Katzenstein HM: Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas. Pediatr Blood Cancer. 59:854–858. 2012. View Article : Google Scholar : PubMed/NCBI
7	Fox E, Patel S, Wathen JK, Schuetze S, Chawla S, Harmon D, Reinke D, Chugh R, Benjamin RS and Helman LJ: Phase II study of sequential gemcitabine followed by docetaxel for recurrent Ewing sarcoma, osteosarcoma, or unresectable or locally recurrent chondrosarcoma: Results of Sarcoma Alliance for Research Through Collaboration Study 003. Oncologist. 17:3212012. View Article : Google Scholar : PubMed/NCBI
8	García-del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, et al: Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: A Spanish Group for Research on Sarcomas study. J Clin Oncol. 29:2528–2533. 2011. View Article : Google Scholar : PubMed/NCBI
9	D'Incalci M and Galmarini CM: A review of trabectedin (ET-743): A unique mechanism of action. Mol Cancer Ther. 9:2157–2163. 2010. View Article : Google Scholar : PubMed/NCBI
10	GarciaCarbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, et al: Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol. 22:1480–1490. 2004. View Article : Google Scholar : PubMed/NCBI
11	LeCesne A, Blay JY, Judson I, van Oosterom A, Verweij J, Radford J, Lorigan P, Rodenhuis S, Ray-Coquard I, Bonvalot S, et al: Phase II study of ET-743 in advanced soft tissue sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 23:576–584. 2005. View Article : Google Scholar : PubMed/NCBI
12	Yovine A, Riofrio M, Blay JY, Brain E, Alexandre J, Kahatt C, Taamma A, Jimeno J, Martin C, Salhi Y, et al: Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol. 22:890–899. 2004. View Article : Google Scholar : PubMed/NCBI
13	Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, et al: Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: Results of a randomized phase II study of two different schedules. J Clin Oncol. 27:4188–4196. 2009. View Article : Google Scholar : PubMed/NCBI
14	LeCesne A, Cresta S, Maki RG, Blay JY, Verweij J, Poveda A, Casali PG, Balaña C, Schöffski P, Grosso F, et al: A retrospective analysis of antitumor activity with trabectedin in translocation-related sarcomas. Eur J Cancer. 48:3036–3044. 2012. View Article : Google Scholar : PubMed/NCBI
15	Pink D, BertzLepel J, Busemann C, Bitz U and Reichardt P: Efficacy of trabectedin in patients with advanced or metastatic alveolar soft-part sarcoma. Onkologie. 35:249–252. 2012. View Article : Google Scholar : PubMed/NCBI
16	Grosso F, Dileo P, Sanfilippo R, Stacchiotti S, Bertulli R, Piovesan C, Jimeno J, D'Incalci M, Gescher A and Casali PG: Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma. Eur J Cancer. 42:1484–1490. 2006. View Article : Google Scholar : PubMed/NCBI
17	Sanfilippo R, Dileo P, Blay JY, Constantinidou A, Le Cesne A, Benson C, Vizzini L, Contu M, Daldi GG, Dei Tos AP and Casali PG: Trabectedin in advanced synovial sarcomas: A multicenter retrospective study from four European institutions and the Italian Rare Cancer Network. Anticancer Drugs. 26:678–681. 2015.PubMed/NCBI
18	Takahashi S, Araki N, Sugiura H, Ueda T, Takahashi M, Morioka H, Yonemoto T, Hiraga H, Hiruma T, Kunisada T, et al: A randomized phase II study comparing trabectedin (T) and best supportive care (BSC) in patients (pts) with translocation-related sarcomas (TRS). J Clin Oncol (ASCO Annual Meeting abstracts). 32:((Suppl; abstr 10524)). 5s2014.
19	Grohar PJ, Griffin LB, Yeung C, Chen QR, Pommier Y, Khanna C, Khan J and Helman LJ: Ecteinascidin 743 interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. Neoplasia. 13:145–153. 2011. View Article : Google Scholar : PubMed/NCBI
20	Lau L, Supko JG, Blaney S, Hershon L, Seibel N, Krailo M, Qu W, Malkin D, Jimeno J, Bernstein M, et al: A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A Children's Oncology Group study. Clin Cancer Res. 11:672–677. 2005.PubMed/NCBI
21	Chu Q, Mita A, Forouzesh B, Tolcher AW, Schwartz G, Nieto A, SotoMatos A, Alfaro V, Lebedinsky C and Rowinsky EK: Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors. Clin Cancer Res. 16:2656–2665. 2010. View Article : Google Scholar : PubMed/NCBI
22	Dileo P, Grosso F, Casanova M, Jimeno J, Marsoni S, Sanfilippo R, Podda M, Ferrari S, Bertulli R and Casali P: Trabectedin (T) in metastatic Ewing's family tumors (EFT) patients (pts) progressing after standard chemotherapy. Journal of Clinical Oncology, 2007. In: ASCO Annual Meeting Proceedings (Post-Meeting Edition). 25(18S): (June 20 Supplement). pp. 100402007
23	Baruchel S, Pappo A, Krailo M, Baker KS, Wu B, Villaluna D, LeeScott M, Adamson PC and Blaney SM: A phase II trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: A report from the Children's Oncology Group. Eur J Cancer. 48:579–585. 2012. View Article : Google Scholar : PubMed/NCBI
24	Grohar PJ, Segars LE, Yeung C, Pommier Y, D'Incalci M, Mendoza A and Helman LJ: Dual targeting of EWS-FLI1 activity and the associated DNA damage response with trabectedin and SN38 synergistically inhibits Ewing sarcoma cell growth. Clin Cancer Res. 20:1190–1203. 2014. View Article : Google Scholar : PubMed/NCBI
25	Cesne AL, Judson I, Maki R, Grosso F, Schuetze S, Mehren MV, Chawla SP, Demetri GD, Nieto A, Tanovic A and Blay JY: Trabectedin is a feasible treatment for soft tissue sarcoma patients regardless of patient age: A retrospective pooled analysis of five phase II trials. Br J Cancer. 109:1717–1724. 2013. View Article : Google Scholar : PubMed/NCBI