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Severe and prolonged lymphopenia observed in patients treated with bendamustine and erlotinib for metastatic triple negative breast cancer

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Triple negative breast cancers (TNBC) frequently have high epidermal growth factor receptor (EGFR) expression and are sensitive to DNA-damaging agents. Improved therapies are needed for this aggressive malignancy.

Patients and methods

We performed a phase I trial of bendamustine and erlotinib, an EGFR tyrosine kinase inhibitor, in patients with metastatic TNBC, ECOG performance status ≤2, and ≤1 prior chemotherapy for metastatic disease. Each 28-day cycle included intravenous bendamustine on days 1, 2 and oral erlotinib on days 5–21 with dose escalation according to a 3 + 3 phase I study design. Dose-limiting toxicity (DLT) was determined by toxicities related to study therapy observed during cycle 1.

Results

Eleven patients were treated, 5 on dose level 1 and 6 on dose level 2. One patient had DLT on dose level 2. However, cumulative toxicities were observed, including grade 3/4 lymphopenia in 91 % (95 % CI 0.59–0.998) with progressively decreased CD4 counts and grade ≥3 infections in 36 % (95 % CI 0.11–0.69) of patients.

Conclusions

Combination therapy with bendamustine and erlotinib causes excessive toxicity with severe, prolonged lymphopenia, depressed CD4 counts, and opportunistic infections and should not be pursued further. Future trials of bendamustine combinations in TNBC patients should account for potential cumulative lymphocyte toxicity necessitating patient monitoring during and after treatment.

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Acknowledgments

This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Cephalon, Inc. Study supply of bendamustine was supplied by Cephalon, Inc. Study supply of erlotinib was provided by Genentech/OSI Pharmaceuticals.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The clinical trial described in this manuscript complies with the current laws of the country in which it was performed (USA).

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University Comprehensive Cancer Center, B411 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH, 43210, USA

    Rachel M. Layman, Ewa Mrozek, Bhuvaneswari Ramaswamy, Maryam B. Lustberg, Robert Wesolowski & Charles L. Shapiro

  2. Center for Biostatistics, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Amy S. Ruppert

  3. Comprehensive Cancer Center Clinical Trials Office, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Susan Ottman & Sarah Carothers

  4. Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Anissa Bingman & Eric H. Kraut

  5. Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Raquel Reinbolt

  6. Department of Hematology/Oncology, Nationwide Children’s Hospital, Columbus, OH, USA

    Melinda Lynn

Authors
  1. Rachel M. Layman
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  2. Amy S. Ruppert
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  3. Melinda Lynn
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  4. Ewa Mrozek
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  5. Bhuvaneswari Ramaswamy
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  6. Maryam B. Lustberg
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  7. Robert Wesolowski
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  8. Susan Ottman
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  9. Sarah Carothers
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  10. Anissa Bingman
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  11. Raquel Reinbolt
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  12. Eric H. Kraut
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  13. Charles L. Shapiro
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Corresponding author

Correspondence to Rachel M. Layman.

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Layman, R.M., Ruppert, A.S., Lynn, M. et al. Severe and prolonged lymphopenia observed in patients treated with bendamustine and erlotinib for metastatic triple negative breast cancer. Cancer Chemother Pharmacol 71, 1183–1190 (2013). https://doi.org/10.1007/s00280-013-2112-2

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  • DOI: https://doi.org/10.1007/s00280-013-2112-2

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