Combination of letrozole, metronomic cyclophosphamide and sorafenib is well-tolerated and shows activity in patients with primary breast cancer

L. Bazzola, C. Foroni, D. Andreis, V. Zanoni, M. R. Cappelletti, G. Allevi, S. Aguggini, C. Strina, M. Milani, S. Venturini, F. Ferrozzi, R. Giardini, R. Bertoni, H. Turley, K. Gatter, P. G. Petronini, S. B. Fox, A. L. Harris, M. Martinotti, A. BerrutiA. Bottini, A. R. Reynolds, D. Generali

Research output: Contribution to journalArticle

Abstract

Purpose: To assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC). Methods: Thirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers. Results: Adequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by 18FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalBritish Journal of Cancer
Volume112
Issue number1
DOIs
Publication statusPublished - Jan 6 2015

Keywords

  • breast cancer
  • endocrine resistance
  • letrozole
  • neoadjuvant
  • primary hormone therapy
  • sorafenib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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    Bazzola, L., Foroni, C., Andreis, D., Zanoni, V., Cappelletti, M. R., Allevi, G., Aguggini, S., Strina, C., Milani, M., Venturini, S., Ferrozzi, F., Giardini, R., Bertoni, R., Turley, H., Gatter, K., Petronini, P. G., Fox, S. B., Harris, A. L., Martinotti, M., ... Generali, D. (2015). Combination of letrozole, metronomic cyclophosphamide and sorafenib is well-tolerated and shows activity in patients with primary breast cancer. British Journal of Cancer, 112(1), 52-60. https://doi.org/10.1038/bjc.2014.563