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Targeting the EWS–FLI1 transcription factor in Ewing sarcoma

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Abstract

Purpose

Preclinical data indicate there is strong synergism of action against Ewing sarcoma in sequential treatment with trabectedin followed by irinotecan and it appears to be related to a selective blockade of the transcription factor EWS–FLI1. This combination was evaluated in Ewing sarcoma patient who was progressing with standard therapies.

Methods

Trabectedin was given as a 24-h iv infusion on day 1 at the dose of 1 mg/sqm, and irinotecan 75 mg/sqm on day 2 and then on days 2 and 4, every 3 weeks from the seventh course.

Results

The therapy was well tolerated with transient hematological toxicity and transaminitis and induced stabilization of the disease lasting for 11 courses, with clinical improvement and marked reduction of the need for opioids. However, shortly before the 12th course, sudden death occurred, possibly due to cerebral stroke, presumably not related to the drug treatment.

Conclusions

The encouraging clinical benefit observed with the combination and its good tolerability deserves further investigation in Ewing sarcoma.

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Conflict of interest

The authors declare that they have no conflict of interest, except M. D. who has received honoraria from Pharma Mar for Scientific Boards.

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Authors and Affiliations

  1. Medical Oncology Unit, I.R.C.C.S. Salvatore Maugeri Foundation, Via Salvatore Maugeri, 10, 27100, Pavia, Italy

    R. Tancredi, G. A. DaPrada, V. Fregoni & L. Pavesi

  2. Medical Oncology Unit, Azienda Ospedaliera Giovanni XXIII, Piazza OMS - Organizzazione Mondiale della Sanità, 1, 24127, Bergamo, Italy

    A. Zambelli

  3. Medical Oncology Unit, Department of Internal Medicine, University of Pavia, P.le Golgi 2, 27100, Pavia, Italy

    A. Riccardi

  4. Department of Pediatrics and Children’s Cancer Research Center (CCRC), Technische Universität München (TUM), Kölner Platz 1, 80804, Munich, Germany

    S. Burdach

  5. Monroe Carrell Jr. Children’s Hospital and the Vanderbilt Ingram Cancer Center, 2201 West End Ave, Nashville, TN, 37235, USA

    P. J. Grohar

  6. Laboratory of Cancer Pharmacology, Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via G. La Masa 19, 20156, Milan, Italy

    M. D’Incalci

Authors
  1. R. Tancredi
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  2. A. Zambelli
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  3. G. A. DaPrada
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  4. V. Fregoni
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  5. L. Pavesi
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  6. A. Riccardi
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  7. S. Burdach
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  8. P. J. Grohar
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  9. M. D’Incalci
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Corresponding author

Correspondence to M. D’Incalci.

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Tancredi, R., Zambelli, A., DaPrada, G.A. et al. Targeting the EWS–FLI1 transcription factor in Ewing sarcoma. Cancer Chemother Pharmacol 75, 1317–1320 (2015). https://doi.org/10.1007/s00280-015-2726-7

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  • DOI: https://doi.org/10.1007/s00280-015-2726-7

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