%0 Journal Article
%T Evaluation of Acute Locoregional Toxicity in Patients with Breast Cancer Treated with Adjuvant Radiotherapy in Combination with Pazopanib
%A Sharad Goyal
%A Sneha Shah
%A Atif J. Khan
%A Hasan Danish
%A Bruce G. Haffty
%J ISRN Oncology
%D 2012
%R 10.5402/2012/896202
%X Purpose. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent pazopanib and RT. Materials and Methods. Patients with breast cancer who received pazopanib in combination with radiation were identified and matched (2£¿:£¿1) to patients with breast cancer who did not receive pazopanib by use of chemotherapy, radiation field design, and radiation dose. Toxicity was scored by the Common Terminology Criteria for Adverse Events and statistical analysis was performed. Results. Grade 1 or 2 radiation dermatitis was seen in 100% and 84% of pazopanib and RT patients and matched controls respectively (P = NS). None of the patients receiving pazopanib and RT experienced ¡Ý grade 3 toxicity within the irradiated volume; three (16%) matched patients experienced a grade 3 skin reaction (P = 0.05). Interestingly, grade 1 or 2 hyperpigmentation was seen in 17% of pazopanib and RT patients and 60% of matched controls (P = 0.005). Conclusion. The addition of concurrent pazopanib and RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated. 1. Introduction The response of a tumor to ionizing radiation is dependent on several factors both intrinsic and extrinsic to the cancer cells. Intrinsic mechanisms of radioresistance include alteration of gene and protein expression resulting in selection of resistant variants [1]. The extrinsic tumor microenvironment varies anisotropically within a mass and is characterized by oxygen depletion, acidosis, glucose deprivation, and high lactate levels [2, 3]. Hypoxic cells are known to be resistant to the effects of radiation as oxygen is required to fix damage conferred by free radicals created by the ionizing radiation. Severely hypoxic cells can have an oxygen enhancement ratio of 2-3; this means they require 2-3 times the radiation dose of well-oxygenated cells for the same level of killing. The tumor microenvironment is shaped by both the metabolic activity of cancer cells and circulation. For growth and survival, tumor cells and stroma secrete proangiogenic factors including FGF, PDGF, and the predominant factor VEGF, which result in endothelial cell migration and proliferation. This helps create new vessels often which are poorly functional with sluggish blood flow since VEGF causes vessel leakage and is expressed out of proportion to other angiogenic factors. This may result in persistent areas of hypoxia [1]. Therapies targeted at VEGF and other angiogenic factors are an active area of
%U http://www.hindawi.com/journals/isrn.oncology/2012/896202/