Increased mean corpuscular volume of red blood cells predicts response to metronomic capecitabine and cyclophosphamide in combination with bevacizumab

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Abstract

Background: There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer. Methods: During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response. Results: During the course of treatment 42 out of 69 patients (61%) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV≥100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95% CI, 0.22-0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p = 0.023). Conclusion: Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab.

Original languageEnglish
Pages (from-to)309-313
Number of pages5
JournalBreast
Volume21
Issue number3
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Erythrocyte Indices
Cyclophosphamide
Erythrocytes
Breast Neoplasms
Disease Progression
Therapeutics
Bevacizumab
Capecitabine
Thymidylate Synthase
Hemoglobins

Keywords

  • Angiogenesis
  • Bevacizumab
  • Macrocytosis
  • Metastatic breast cancer
  • Metronomic chemotherapy
  • Predictive factor

ASJC Scopus subject areas

  • Surgery

Cite this

@article{9bd4b57e77c44d5f90c91a93a8afc60f,
title = "Increased mean corpuscular volume of red blood cells predicts response to metronomic capecitabine and cyclophosphamide in combination with bevacizumab",
abstract = "Background: There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer. Methods: During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response. Results: During the course of treatment 42 out of 69 patients (61{\%}) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV≥100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95{\%} CI, 0.22-0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p = 0.023). Conclusion: Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab.",
keywords = "Angiogenesis, Bevacizumab, Macrocytosis, Metastatic breast cancer, Metronomic chemotherapy, Predictive factor",
author = "Silvia Dellapasqua and Vincenzo Bagnardi and Francesco Bertolini and Sandri, {Maria Teresa} and Davide Pastrello and Giuseppe Cancello and Emilia Montagna and Alessandra Balduzzi and Patrizia Mancuso and Alberto Luini and Aron Goldhirsch and Marco Colleoni",
year = "2012",
month = "6",
doi = "10.1016/j.breast.2012.01.015",
language = "English",
volume = "21",
pages = "309--313",
journal = "Breast",
issn = "0960-9776",
publisher = "Churchill Livingstone",
number = "3",

}

TY - JOUR

T1 - Increased mean corpuscular volume of red blood cells predicts response to metronomic capecitabine and cyclophosphamide in combination with bevacizumab

AU - Dellapasqua, Silvia

AU - Bagnardi, Vincenzo

AU - Bertolini, Francesco

AU - Sandri, Maria Teresa

AU - Pastrello, Davide

AU - Cancello, Giuseppe

AU - Montagna, Emilia

AU - Balduzzi, Alessandra

AU - Mancuso, Patrizia

AU - Luini, Alberto

AU - Goldhirsch, Aron

AU - Colleoni, Marco

PY - 2012/6

Y1 - 2012/6

N2 - Background: There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer. Methods: During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response. Results: During the course of treatment 42 out of 69 patients (61%) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV≥100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95% CI, 0.22-0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p = 0.023). Conclusion: Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab.

AB - Background: There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer. Methods: During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response. Results: During the course of treatment 42 out of 69 patients (61%) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV≥100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95% CI, 0.22-0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p = 0.023). Conclusion: Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab.

KW - Angiogenesis

KW - Bevacizumab

KW - Macrocytosis

KW - Metastatic breast cancer

KW - Metronomic chemotherapy

KW - Predictive factor

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U2 - 10.1016/j.breast.2012.01.015

DO - 10.1016/j.breast.2012.01.015

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