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Phase II trial of ifosfamide in combination with the VEGFR inhibitor sorafenib in advanced soft tissue sarcoma: a Spanish group for research on sarcomas (GEIS) study

  • PHASE II STUDIES
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Summary

Background Sorafenib is a potent targeted-therapy that blockades angiogenesis and has demonstrated activity against some sarcoma subtypes. Preclinical studies suggested that treatment with sorafenib plus cytotoxic agents could result in additive efficacy. Methods Patients with advanced soft tissue sarcoma, with or without anthracycline pretreatment were included. Patients received oral sorafenib 400 mg twice daily starting on Day +2, ifosfamide 2.0 g/m2 iv infusion lasting 4 h on days 1, 2 and 3 with concurrent mesna 400 mg/m2 every three weeks until disease progression or unacceptable toxicity or up to a maximum of 6 cycles of ifosfamide (sorafenib could be continued until progressive disease or unacceptable toxicity). Primary objective was progression-free rate (PFR) at 3 and 6 months; secondary objectives were overall response rate (ORR), Progression-free survival (PFS), Overall survival (OS) and safety. This article reports the phase II part of a phase I/II clinical trial. Results Thirty-five patients were enrolled. PFR at 3 and 6 months was 66% (95% CI 48–81) and 37% (95% CI 22–55). Six patients (17%) achieved partial response and 17 (49%) stable disease. Median PFS was 4.8 months (CI 95% 1.94–6.36) and overall survival 16.2 months (95% CI 8.75-NA). Conclusion Treatment with sorafenib plus ifosfamide achieved a significant clinical benefit with an acceptable safety profile in patients with advanced soft tissue sarcoma resistant to anthracyclines, which warrants a more detailed study in randomized clinical trials.

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Acknowledgments

This work was supported by Bayer HealthCare. Sonia Maciá and Daniela Morales (PIVOTAL S.L.) provided advice to properly handle and submit the paper.

Funding

This study was funded by Bayer España.

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Authors and Affiliations

  1. Institut Catalá d’Oncologia Hospitalet, Barcelona, Spain

    Xavier García del Muro

  2. Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain

    Joan Maurel

  3. Hospital Miguel Servet, Zaragoza, Spain

    Javier Martínez Trufero

  4. Instituto Valenciano de Oncología, Valencia, Spain

    Javier Lavernia

  5. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Antonio López Pousa

  6. Hospital Provincial Castellón, Castelló, Spain

    Ramón de las Peñas

  7. Hospital Puerta de Hierro, Madrid, Spain

    Ricardo Cubedo

  8. Hospital General de Asturias, Madrid, Spain

    José Pablo Berros

  9. Hospital Clínico de Madrid, Madrid, Spain

    Antonio Casado Herráez

  10. Hospital Marqués de Valdecilla, Santander, Spain

    Ana de Juan

  11. Hospital Virgen del Rocío, Sevilla, Spain

    Javier Martín Broto

Authors
  1. Xavier García del Muro
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  2. Joan Maurel
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  3. Javier Martínez Trufero
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Corresponding author

Correspondence to Xavier García del Muro.

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Conflict of interest

Xavier García del Muro: XG has received research grants from Bayer and Astra Zeneca. XG has received a speaker honorarium from Pfizer, Lilly, Novartis, Ipsen and BMS.

Javier Martín Broto: Consulting or Advisory Role from PharmaMar, GSK, Novartis, Amgen, Bayer, Lilly.

Rest of the authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Disclosure

The authors have no relevant affiliations or financial involvements with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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García del Muro, X., Maurel, J., Martínez Trufero, J. et al. Phase II trial of ifosfamide in combination with the VEGFR inhibitor sorafenib in advanced soft tissue sarcoma: a Spanish group for research on sarcomas (GEIS) study. Invest New Drugs 36, 468–475 (2018). https://doi.org/10.1007/s10637-018-0583-z

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  • DOI: https://doi.org/10.1007/s10637-018-0583-z

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