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Bevacizumab reduces VEGF expression in patients with relapsed and refractory acute myeloid leukemia without clinical antileukemic activity

Leukemia volume 21, pages 1310–1312 (2007)Cite this article

Angiogenesis is an absolute requirement for tumor growth and metastasis, and is an attractive target for biologically based cancer therapies. Vascular endothelial growth factor (VEGF, VEGF-A) is one of the most potent promoters of angiogenesis whose functions are mainly mediated through the tyrosine kinase receptor VEGFR-2 (also known as KDR or Flk-1). Comparable to solid tumors, there is growing evidence that the VEGF/VEGFR2 signaling pathway plays an important role in leukemic cell growth.1, 2, 3, 4 Clinical trials with VEGF inhibition in a variety of malignancies are ongoing. The best-studied and most advanced approach to VEGF inhibition is the recombinant humanized monoclonal antibody bevacizumab (BV). We have treated patients with relapsed or refractory acute myeloid leukemia (AML), not qualifying for further intensive cytotoxic chemotherapy, in order to investigate single agent BV in AML. Nine patients were treated between May 2005 and May 2006. All patients signed informed consent before enrollment.

A summary of baseline patient characteristics is shown in Table 1. Patients were between 46 and 81 years old (median: 63 years), not medically fit to endure further conventional chemotherapy. Refractory AML was defined as primary resistance against at least two induction therapy regimens or relapsed patients who were refractory against at least one reinduction protocol. Seven patients suffered from refractory AML (three primary induction failure, four refractory to ⩾2 induction regimens, or to reinduction after first relapse). Two patients had AML in first relapse (median duration of first complete remission (CR) 7 months; range 7–9 months) of whom one patient had secondary AML evolved from chronic myelomonocytic leukemia. Cytogenetics was abnormal in seven patients, including trisomy 8 and complex cytogenetics (Table 1). All patients had received dose-intensive infusional ara-C and/or high-dose bolus ara-C in combination with anthracycline or mitoxantrone as induction and/or consolidation regimens. BV (Avastin, Roche Pharma) at a dose of 10 mg/kg body weight was administered as a single i.v. infusion over 60–90 min on days 1, 14 and 35 (cycle 1–3). Acetaminophen and antihistamines (clemastin, ranitidin) were administered before infusion to reduce the risk of allergic reactions.

Table 1 Baseline patient characteristics
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Authors and Affiliations

  1. Department of Medicine/Haematology and Oncology, University of Muenster, Muenster, Germany

    L Zahiragic, C Schliemann, R Bieker, N H Thoennissen, K Burow, C Kramer, M Zühlsdorf, W E Berdel & R M Mesters

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  1. L Zahiragic
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  2. C Schliemann
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  3. R Bieker
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  4. N H Thoennissen
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Correspondence to R M Mesters.

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Zahiragic, L., Schliemann, C., Bieker, R. et al. Bevacizumab reduces VEGF expression in patients with relapsed and refractory acute myeloid leukemia without clinical antileukemic activity. Leukemia 21, 1310–1312 (2007). https://doi.org/10.1038/sj.leu.2404632

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