Aromatase Inhibition and Capecitabine Combination as 1^stor 2^ndLine Treatment for Metastatic Breast Cancer - a Retrospective Analysis

Abstract

Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and capecitabine in estrogen receptor (ER)-positive cell lines enhance antitumor efficacy. This retrospective analysis of a group of patients with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined AI with capecitabine. Materials and Methods: Patients with hormone receptor-positive metastatic breast cancer treated between 1st January 2005 and 31st December 2010 with a combination of capecitabine and AI were evaluated and outcomes were compared with those of women treated with capecitabine in conventional dose or AI as a monotherapy. Results: Of 72 patients evaluated, 31 received the combination treatment, 22 AI and 19 capecitabine. The combination was used in 20 patients as first-line and 11 as second-line treatment. Mean age was 46.2 years with a range of 28-72 years. At the time of progression, 97% had a performance status of <2 and 55% had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow up was 38 months with a range of 16-66 months. The median PFS of first-line treatment was significantly better for the combination (PFS 21 months vs 8.0 months for capecitabine and 15.0 months for AI). For second-line treatment, the PFS was longer in the combination compared with capecitabine and Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year and 5 year survival did not show any significant differences among combination and monotherapy groups. The most common adverse events for the combination group were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) and grade 1 diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported. Conclusions: Combination treatment with capecitabine and AI used as a first line or second line treatment was safe with much lowered toxicity. Prospective randomized clinical trials should evaluate the use of combination therapy in advanced breast cancer to confirm these findings.

Capecitabine Plus Aromatase Inhibitor as First Line Therapy for Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer

“…Capecitabine is a cytotoxic oral drug with an adequate safety profile and strong evidence of effectiveness in MCh studies [27]. It was proven to be effective in combination with AI, showing favorable outcomes in several clinical trials [28][29][30][31][32][33]. In 2015, Shankar et al reported median progression free survival (mPFS) of 21 months for chemoendocrine therapy, 15 months for AI, and 8 months for capecitabine alone [28].…”

“…It was proven to be effective in combination with AI, showing favorable outcomes in several clinical trials [28][29][30][31][32][33]. In 2015, Shankar et al reported median progression free survival (mPFS) of 21 months for chemoendocrine therapy, 15 months for AI, and 8 months for capecitabine alone [28]. Moreover, a recent phase II clinical trial showed that metronomic capecitabine combined with AIs had good efficacy, minimal toxicity, and good tolerance [31].…”

Association of Cytidine Deaminase Polymorphism with Capecitabine Effectiveness in Breast Cancer Patients

“…Capecitabine was specifically designed for oral administration, to deliver 5-fluorouracil (5-FU) to the tumor site and to avoid systemic 5-FU exposure. Oral capecitabine is highly effective for the management of breast and colorectal cancer (Kaklamani and Gradishar, 2003;Shankar et al, 2015). By using a three-step enzymatic cascade, the innovative oral fluoropyrimidine carbamate capecitabine (Xeloda) preferentially produces 5-FU in tumor tissue.…”