Original Article

Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 5, pp 1183-1190

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

  • Rachel M. LaymanAffiliated withDivision of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University Comprehensive Cancer Center Email author 
  • , Amy S. RuppertAffiliated withCenter for Biostatistics, The Ohio State University Comprehensive Cancer Center
  • , Melinda LynnAffiliated withDepartment of Hematology/Oncology, Nationwide Children’s Hospital
  • , Ewa MrozekAffiliated withDivision of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University Comprehensive Cancer Center
  • , Bhuvaneswari RamaswamyAffiliated withDivision of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University Comprehensive Cancer Center
  • , Maryam B. LustbergAffiliated withDivision of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University Comprehensive Cancer Center
  • , Robert WesolowskiAffiliated withDivision of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University Comprehensive Cancer Center
  • , Susan OttmanAffiliated withComprehensive Cancer Center Clinical Trials Office, The Ohio State University Comprehensive Cancer Center
  • , Sarah CarothersAffiliated withComprehensive Cancer Center Clinical Trials Office, The Ohio State University Comprehensive Cancer Center
    • , Anissa BingmanAffiliated withDivision of Hematology, The Ohio State University Comprehensive Cancer Center
    • , Raquel ReinboltAffiliated withDepartment of Internal Medicine, The Ohio State University Comprehensive Cancer Center
    • , Eric H. KrautAffiliated withDivision of Hematology, The Ohio State University Comprehensive Cancer Center
    • , Charles L. ShapiroAffiliated withDivision of Medical Oncology, Stefanie Spielman Comprehensive Breast Center, The Ohio State University Comprehensive Cancer Center

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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.

Keywords

Bendamustine Erlotinib Lymphopenia Triple negative breast cancer Metastatic breast cancer