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Evaluation of low-dose fractionated radiation therapy as a chemopotentiator of gemcitabine in advanced pancreatic cancer: results from an international multi-institutional phase II trial

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Purpose

Potentiation of systemic dosing of gemcitabine using very low-dose fractionated radiotherapy may improve its effect in advanced pancreatic cancer without additional toxicity as suggested by the results of our multi-institutional phase II study. Future regimens combining low-dose fractionated radiotherapy (RT) with systemic chemotherapy should be assessed for improving the chemotherapeutic benefit.

Objective

Until recently, gemcitabine was considered the standard treatment for advanced pancreatic cancer despite low response rates. Efforts to improve response rates by combination therapies have had limited success and have involved using sub-systemic dosing of gemcitabine as a sensitizer for radiation. A novel paradigm, utilizing low-dose fractionated radiotherapy (LDFRT) as a potentiator of full-dose gemcitabine instead, was explored to assess safety and efficacy in treating advanced pancreatic cancer.

Methods

Patients with locally advanced and metastatic pancreatic cancer were treated with 4 cycles of gemcitabine and LDFRT in a multi-institutional phase II study. Gemcitabine (1250 mg/m2 over 2 h) was administered on days 1 and 8 of a 21-day cycle. LDFRT fields included the upper abdomen from the diaphragm to the iliac crest and were administered at 60 cGy per fraction twice daily on days 1, 2, 8, and 9, with the morning fraction being delivered prior to gemcitabine infusion on days 1 and 8. Primary endpoint was objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST).

Results

Thirty-eight patients were enrolled in the trial, of which 23 had metastatic disease at time of enrollment. Objective response rate (CR + PR) was 8 %, and 61 % had at least stable disease. Overall median survival was 13 months and 1-year survival was 37 %. Patients with non-metastatic disease had a 1-year survival of 60 %. The most significant toxicity was hematologic, and only 3 patients were withdrawn from protocol due to toxicity. There was no reported febrile neutropenia.

Conclusion

The use of LDFRT with systemic gemcitabine is safe, tolerable, and potentially effective. In advanced pancreatic cancer, where response rates with single-agent gemcitabine have been low, this chemopotentiation paradigm may improve survival among a poor prognostic patient cohort.

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Funding information

This study was funded by Eli Lilly and Company, 555 12th St. NW, Washington, DC.

Conflict of interest

The authors declare that they have no competing interests.

Statement of ethical standards

All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

This research was performed on a protocol approved by the institutional review board of each of the participating institutions and as per the guidelines for ethical research at each participating institution.

Statement of informed consent

All persons gave their informed consent prior to their inclusion in the study.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Maryland, 22 S. Greene Street, Gudelsky Basement, Baltimore, MD, 21201, USA

    Navesh K. Sharma, Nancy L. Kennedy & William F. Regine

  2. Department of Medicine, University of Maryland, Baltimore, MD, 21201, USA

    Naimish B. Pandya

  3. Department of Oncology, McMaster University, Hamilton, ON, Canada

    Raimond K. Wong & Pierre P. Major

  4. Department of Radiation Oncology, Johns Hopkins University, Baltimore, MD, USA

    Joseph M. Herman

  5. Department of Surgery, University of Maryland, Baltimore, MD, USA

    Nader N. Hanna & H. Richard Alexander

  6. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Daniel A. Laheru

Authors
  1. Navesh K. Sharma
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  2. Naimish B. Pandya
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  3. Raimond K. Wong
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  7. Pierre P. Major
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  8. H. Richard Alexander
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  9. Nancy L. Kennedy
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  10. William F. Regine
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Correspondence to Navesh K. Sharma.

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Participating institutions

University of Maryland, University of Kentucky, Johns Hopkins University, McMaster University.

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Sharma, N.K., Pandya, N.B., Wong, R.K. et al. Evaluation of low-dose fractionated radiation therapy as a chemopotentiator of gemcitabine in advanced pancreatic cancer: results from an international multi-institutional phase II trial. J Radiat Oncol 4, 401–409 (2015). https://doi.org/10.1007/s13566-015-0213-8

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  • DOI: https://doi.org/10.1007/s13566-015-0213-8

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