Effect of increased body mass index (BMI) on time to tumour progression (TTP) in unresectable metastatic colorectal cancer (mCRC) patients treated with bevacizumab-based therapy

N Faruk Aykan,Rian Disci,Burak Sakar,Rumeysa Ciftci,Leyla Kilic,Serkan Keskin,Fatma Sen,Senem Karabulut,Ibrahim Yildiz

doi:10.1007/s12032-013-0679-4

Abstract

High BMI is a well-known risk factor for the development and recurrence of several solid tumours, including CRC. Obesity is associated with increased levels of vascular endothelial growth factor (VEGF). Bevacizumab is the main targeted therapy for inhibiting tumour angiogenesis by blocking the VEGF/VEGF receptor pathway. Elevated VEGF in obese patients might provoke resistance to anti-VEGF therapy. We evaluated the efficacy of bevacizumab on TTP among mCRC patients through stratifying them according to their BMI. Patients with mCRC who had been treated with fluoropyrimidine-based combination chemotherapy with bevacizumab were included in the study. Patients were assigned according to their BMI before initiation of therapy (group A: BMI < 25 kg/m2, group B: BMI ≥ 25 kg/m2). Multivariate analysis was performed to evaluate the risk of tumour progression. Between April 2007 and June 2011, 80 patients were treated with chemotherapy and bevacizumab as first-line therapy (n = 37 for group A, n = 43 for group B). Tumours in 56.3 % of the patients in group A (n = 21) and 76.3 % of the patients in group B (n = 33) progressed during a median 10-months (3–57 months) follow-up. The median TTP was 11.7 months in the group A and 6 months in the group B (p = 0.004). In a multivariate analysis, high BMI (≥25 kg/m2) was associated with significantly shorter TTP (p = 0.01; HR: 4.37). High BMI among mCRC patients treated with bevacizumab is associated with shorter TTP. Further study in larger databases is warranted for confirming the negative prognostic effect of obesity during treatment with anti-VEGF agents.

Highlights

High BMI is a well-known risk factor for the development and recurrence of several solid tumours, including CRC
We evaluated the efficacy of bevacizumab on time to progression (TTP) among mCRC patients through stratifying them according to their BMI
The clinical and demographic data of 54 metastatic CRC patients who had disease progression during chemotherapy with bevacizumab were summarised in Table 1 and 2

Summary

Introduction

High BMI is a well-known risk factor for the development and recurrence of several solid tumours, including CRC. Obesity is associated with increased levels of vascular endothelial growth factor (VEGF). BMI among mCRC patients treated with bevacizumab is associated with shorter TTP. Increasing epidemiological evidence has demonstrated that obesity is associated with an increased risk of cancer, especially colon cancer [2,3,4] Several factors, such as insulin resistance, increased levels of leptin, plasminogen activator inhibitor-1, endogenous sex steroids, decreased levels of adiponectin, and chronic inflammation, are involved in carcinogenesis and cancer progression [5]. Guiu et al [15] reported that high visceral fat area (VFA) measured by computed tomography independently predicted poorer outcome in a retrospective series of patients given first-line bevacizumab-based therapy for metastatic colon cancer

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Conclusion