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Trofosfamide in the treatment of elderly or frail patients with diffuse large B-cell lymphoma

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

The introduction of immunochemotherapy has led to a significant improvement in treatment results and prognosis of diffuse large B-cell non-Hodgkins lymphoma (DLBCL) both at initial diagnosis and in relapse. Trofosfamide, an oxazaphosphorine derivative, has been utilized as alternative treatment option for patients with lymphoproliferative diseases unsuitable for conventional chemotherapy agents and protocols because of age, comorbidity, or poor performance score. While data on the activity and safety of single-agent trofosfamide have been published, the potential value of this agent in immunochemotherapy in combination with anti-CD20 antibodies such as rituximab has not been investigated to our knowledge.

Methods

Safety and therapeutic effectiveness of trofosfamide given orally at a dose of 50 mg twice daily alone, or in combination with standard-dose rituximab, was investigated in a cohort of elderly and/or highly comorbid patients with histologically confirmed primary or secondary DLBCL.

Results

Treatment with trofosfamide in this combination setting was generally well tolerated with no treatment-related deaths and manageable side effects, most of which were WHO class I–II; the most clinically relevant toxicity was cytopenia. 19 of 21 examined patients responded to therapy with 11 of 21 (52.4%) achieving a complete remission (CR). Median overall and progression-free survival (OS and PFS) in the CR-group was 14 and 9 months, respectively. In the subgroup with trofosfamide-based first-line therapy, 7 of 10 (70%) achieved CR and median PFS was not reached.

Conclusions

Immunochemotherapy with rituximab and trofosfamide (RT) is safe and effective in elderly and poor-performance patients with DLBCL. Response rates are comparable to most commonly used primary and salvage treatment protocols. The potential value of TR regimen in both first-line and relapsed/refractory DLCBL merits further investigation and is probably underestimated.

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Acknowledgements

The authors would like to thank Svenja Kopelke and Rudina Marx for their administrative support.

Funding

The authors declare no funding source for this study.

Author information

Author notes

  1. Harald Biersack and Niklas Gebauer contributed equally to this study.

Authors and Affiliations

  1. Department of Haematology and Oncology, University Hospital of Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538, Lübeck, Germany

    Hanno M. Witte, Tobias Bartscht, Harald Biersack & Niklas Gebauer

  2. Department of Haematology and Oncology, German Armed Forces Hospital Ulm, Oberer Eselsberg 40, 89081, Ulm, Germany

    Hanno M. Witte, Armin Riecke & Thomas Mayer

  3. Department of Radiation Oncology, University Hospital of Schleswig-Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Dirk Rades

  4. Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Hendrik Lehnert

  5. Reference Center for Lymph Node Pathology and Haematopathology, Lübeck, Germany

    Hartmut Merz

  6. Department of Haematology and Oncology, Sana Hospitals, Lübeck, Germany

    Sebastian Fetscher

Authors
  1. Hanno M. Witte
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  2. Armin Riecke
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  3. Thomas Mayer
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  4. Tobias Bartscht
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  7. Hartmut Merz
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  8. Sebastian Fetscher
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  9. Harald Biersack
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  10. Niklas Gebauer
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Contributions

Study design and drafting of manuscript: NG, HW, HB and DR. Data collection and analysis, revision of manuscript: HW, NG, HL, HM and SF. Revision and final approval of manuscript: all authors.

Corresponding author

Correspondence to Hanno M. Witte.

Ethics declarations

Ethical approval

This study was approved by the ethics committee of the University of Luebeck (Reference no: 17-266) and was conducted in accordance with the Declaration of Helsinki and internationally accepted ethical guidelines.

Informed consent

Upon hospital admission, all participants gave their written informed consent for the storage of personal data and the use of data for research purposes.

Availability of data and materials

Data supporting the conclusions of this article are included in the article.

Conflict of interest

The authors declare that they have no conflict of interest.

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Witte, H.M., Riecke, A., Mayer, T. et al. Trofosfamide in the treatment of elderly or frail patients with diffuse large B-cell lymphoma. J Cancer Res Clin Oncol 145, 129–136 (2019). https://doi.org/10.1007/s00432-018-2772-8

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  • DOI: https://doi.org/10.1007/s00432-018-2772-8

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