A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer

Abstract

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m2 daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller–Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer.

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients

“…Meanwhile, TSTA3 was shown to participate in the biosynthesis of GDP-L-fucose, and the expression level of TSTA3 was correlated with poor prognosis for patients with esophageal squamous cell carcinoma (44). TYMP has been reported to be associated with the conversion of capecitabine to 5-FU (45). Previous study has also indicated that the expression level of TYMP was associated with capecitabine response (46).…”

Evaluation of the clinical benefits of adjuvant capecitabine monotherapy in elderly women with breast cancer: A retrospective study

“…Arowolo et al reported that capecitabine monotherapy achieved good overall response rates with manageable toxicity when administered as neoadjuvant chemotherapy to 16 patients with locally advanced breast cancer (16). In a phase II study by Tolaney et al, 3 patients exhibited a complete clinical response after 4 cycles of capecitabine monotherapy and 8 patients exhibited a partial clinical response among 24 women with operable hormone receptor-positive breast cancer (17). Li et al reviewed the randomized controlled trials that included capecitabine in the neoadjuvant chemotherapy for breast cancer and concluded that adding capecitabine to neoadjuvant chemotherapy was unlikely to improve the outcomes in breast cancer patients without distant metastases (18).…”