A retrospective study evaluating a fixed low dose capecitabine monotherapy in women with HER-2 negative metastatic breast cancer

Abstract

To determine if a low fixed dosing strategy of capecitabine would produce comparable clinical activity with less adverse toxicities compared to published data with higher doses in the setting of metastatic breast cancer (mBC). We retrospectively analyzed patients treated with a low fixed dose of capecitabine (CAPE-L) at 1,000 mg twice daily for 14 days every 21 days. Outcomes included clinical benefit rate (CBR), overall response rates (ORR), time to progression (TTP), and overall survival (OS). A historical comparison group of mBC patients treated on 12 prior trials at the package-insert dose of capecitabine (n = 1,949) was utilized. Eighty-six patients were analyzed in our cohort. Positive hormone receptor status (79.1 vs. 50.6 %), and capecitabine as first-line chemotherapy (44.2 vs. 16.5 %) were more frequent in our cohort relative to the historical comparison. The median starting dose in our cohort was 633.5 mg/m(2). The CBR was similar between the CAPE-L and the standard dose cohorts (55.8 vs. 49.5 %), as was ORR (24.3 vs. 24 %), and median TTP (7 mo, 95 % CI 5.5-8.5 vs. 5.1 mo, 95 % CI 4.5-5.7). Median OS was longer in our cohort (24 mo, 95 % CI 16.8-31.2) than the historic standard dose cohort (12.1 mo, 95 % CI 9.6-14.4), a difference that was likely explained by the higher proportion of patients in the CAPE-L cohort who received capecitabine as first-line chemotherapy and who had hormone receptor positive disease. As expected, adverse events were less frequent with CAPE-L. We found that CAPE-L, which translates into a dose of 600-650 mg/m(2), appeared to have good clinical efficacy and acceptable toxicity.

A comparison of toxicity profiles between the lower and standard dose capecitabine in breast cancer: a systematic review and meta-analysis

“…Ambros and colleagues commonly prescribe capecitabine in their MBC population at a fixed dose of 1000mg bid for 14 of every 21 days within their single large breast-specific oncology group [47]. Given the lack of published data on this dose, they retrospectively analyzed data from 86 patients treated with this regimen (CAPE-L) regardless of the number of prior therapy lines.…”

Comparison of the Therapeutic Efficacy of the Early and the Delayed Use of Vinorelbine-Based Regimens for Patients with Advanced Breast Cancer

“…Due to the ease of administration and comparable efficacy and tolerability compared to other agents, it is commonly used in the first-line metastatic setting [30]. Compared to many other agents used in the treatment of MBC, capecitabine has a greater degree of CNS penetration and can be used in the setting of liver dysfunction [31]. Recent data suggest that capecitabine may be more active in patients with HR-positive MBC.…”

Gemcitabine and Capecitabine Combination Chemotherapy in Patients with Metastatic Breast Cancer Pretreated with Anthracyclines and/or Taxanes

“…There are additional benefits to using capecitabine in the treatment of MBC patients, such as convenience of an oral formulation, ease of dose modification, less gastrointestinal toxicity, and lack of cumulative toxicity over prolonged administration [20]. In addition, capecitabine has shown synergistic effects as well as tolerable toxicity when used in combination with other cytotoxic agents, such as docetaxel, vinorelbine, and gemcitabine [20,21,22]. The synergistic effect of capecitabine plus gemcitabine is likely caused by the inhibition of ribonucleotide reductase and the potentiated binding of 5-monophosphate to thymidylate synthase.…”