Metronomic chemotherapy combined with bevacizumab and erlotinib in patients with metastatic HER2-negative breast cancer: clinical and biological activity.

Abstract

UNLABELLED:

The aim of this study was to determine the safety and efficacy of metronomic chemotherapy combined with targeted drugs in patients with metastatic breast cancer (MBC). We included 26 untreated patients with HER2-negative (HER-) MBC and poor hormone receptor expression. The analysis of the results suggests that the metronomic chemotherapy combined with bevacizumab and erlotinib is effective and well tolerated.

BACKGROUND:

The object of this study was to evaluate the safety and efficacy of metronomic chemotherapy in combination with bevacizumab and erlotinib in patients with HER2-negative (HER2(-)) metastatic breast cancer (MBC) and poor hormone receptor expression.

PATIENTS AND METHODS:

Patients with untreated MBC were candidates to receive metronomic oral capecitabine (500 mg thrice daily) and cyclophosphamide (50 mg daily) plus bevacizumab (15 mg/kg every 3 weeks) and erlotinib (100 mg daily).

RESULTS:

Of 24 patients assessable for response, we observed 1 complete response (CR, 4%), 14 partial responses (58%), 5 patients with stable disease greater than 9 weeks' duration (SD, 21%), and 1 patient (4%) with early progression of disease. The overall clinical benefit (CB) (CR + partial response + SD > 24 weeks) was 75% (95% confidence interval [CI], 53%-90%). Median time to progression was 43 weeks (95% CI, 21-69). Patients with low levels of circulating endothelial progenitors (CEPs) at baseline had a significantly improved progression-free survival (PFS). Toxicity was generally mild. Grade 3 toxicity included diarrhea (n = 1), thrombosis (n = 1), and hypertension (n = 2). Grade 2 adverse events included diarrhea (n = 5), hand-foot syndrome (n = 13), and hypertension (n = 4).

CONCLUSION:

Treatment with metronomic chemotherapy in combination with bevacizumab and erlotinib was effective in HER2(-), estrogen receptor (ER)- and progesterone receptor (PR)-poor advanced breast cancer.

• Authors: Emilia Montagna, Giuseppe Cancello, Vincenzo Bagnardi, Davide Pastrello, Silvia Dellapasqua, Gino Perri, Giuseppe Viale, Paolo Veronesi, Alberto Luini, Mattia Intra, Angelica Calleri, Cristiano Rampinelli, Aron Goldhirsch, Francesco Bertolini, Marco Colleoni
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 12 Issue 3 Pg. 207-14 (Jun 2012) ISSN: 1938-0666 [Electronic] United States
• PMID: 22520733 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers, Pharmacological
• Quinazolines
• Deoxycytidine
• Bevacizumab
• Capecitabine
• Cyclophosphamide
• Erlotinib Hydrochloride
• ERBB2 protein, human
• Receptor, ErbB-2
• Vascular Endothelial Growth Factor Receptor-2
• Fluorouracil

Topics

• Administration, Metronomic
• Adult
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Bevacizumab
• Biomarkers, Pharmacological (analysis, blood, metabolism)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Capecitabine
• Carcinoma (drug therapy, genetics, pathology)
• Cyclophosphamide (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Erlotinib Hydrochloride
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Humans
• Middle Aged
• Neoplasm Metastasis
• Neoplastic Stem Cells (pathology)
• Quinazolines (administration & dosage)
• Receptor, ErbB-2 (genetics)
• Vascular Endothelial Growth Factor Receptor-2 (analysis, metabolism)