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A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer

Investigational New Drugs volume 32, pages 549–554 (2014)Cite this article

Summary

Background Pralatrexate (FotolynTM; Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). Patients and methods This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m2 biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m2 weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Results Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Conclusions Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.

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Acknowledgments

This investigator-initiated trial was supported by a grant from the National Comprehensive Cancer Network (NCCN) and Allos Therapeutics Inc.

Conflict of interest

The authors declare that they have no conflict of interest.

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Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), 300 E 66th Street, New York, NY, 10065, USA

    Alan L. Ho, Brynna L. Lipson, Eric J. Sherman, Matthew G. Fury, Roberta Sales, Lisa Cox & David G. Pfister

  2. Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Alan L. Ho, Eric J. Sherman, Matthew G. Fury & David G. Pfister

  3. Department of Medicine, MSKCC Regional Network Site, Basking Ridge, NJ, USA

    Han Xiao

  4. Department of Medicine, MSKCC Regional Network Site, Rockville Center, New York, NY, USA

    Arlyn Apollo

  5. Department of Medicine, New York University Cancer (NYU) Institute/NYU Medical Center/Bellevue Hospital Center, New York, NY, USA

    Nagashree Seetharamu

  6. Department of Epidemiology and Biostatistics, MSKCC, New York, NY, USA

    Camelia S. Sima

  7. Department of Radiology, MSKCC, New York, NY, USA

    Sofia Haque & John K. Lyo

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  1. Alan L. Ho
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  2. Brynna L. Lipson
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  3. Eric J. Sherman
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  4. Han Xiao
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  5. Matthew G. Fury
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  6. Arlyn Apollo
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  7. Nagashree Seetharamu
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  8. Camelia S. Sima
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  9. Sofia Haque
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  10. John K. Lyo
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  11. Roberta Sales
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  12. Lisa Cox
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  13. David G. Pfister
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Correspondence to Alan L. Ho.

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Ho, A.L., Lipson, B.L., Sherman, E.J. et al. A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer. Invest New Drugs 32, 549–554 (2014). https://doi.org/10.1007/s10637-014-0073-x

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  • DOI: https://doi.org/10.1007/s10637-014-0073-x

Keywords

  • Head and neck cancer
  • Pralatrexate
  • Antifolate
  • HNSCC