Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 5, pp 1183–1190 | Cite as

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

  • Rachel M. Layman
  • Amy S. Ruppert
  • Melinda Lynn
  • Ewa Mrozek
  • Bhuvaneswari Ramaswamy
  • Maryam B. Lustberg
  • Robert Wesolowski
  • Susan Ottman
  • Sarah Carothers
  • Anissa Bingman
  • Raquel Reinbolt
  • Eric H. Kraut
  • Charles L. Shapiro
Original Article



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.


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.


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.


Bendamustine Erlotinib Lymphopenia Triple negative breast cancer Metastatic breast cancer 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Rachel M. Layman
    • 1
  • Amy S. Ruppert
    • 2
  • Melinda Lynn
    • 6
  • Ewa Mrozek
    • 1
  • Bhuvaneswari Ramaswamy
    • 1
  • Maryam B. Lustberg
    • 1
  • Robert Wesolowski
    • 1
  • Susan Ottman
    • 3
  • Sarah Carothers
    • 3
  • Anissa Bingman
    • 4
  • Raquel Reinbolt
    • 5
  • Eric H. Kraut
    • 4
  • Charles L. Shapiro
    • 1
  1. 1.Division of Medical Oncology, Stefanie Spielman Comprehensive Breast CenterThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  2. 2.Center for BiostatisticsThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  3. 3.Comprehensive Cancer Center Clinical Trials OfficeThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  4. 4.Division of HematologyThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  5. 5.Department of Internal MedicineThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  6. 6.Department of Hematology/OncologyNationwide Children’s HospitalColumbusUSA

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