S-1-associated hand-foot syndrome as a prognostic factor in patients with metastatic breast cancer

Abstract

Purpose: S-1, an orally administered fluorinated pyrimidine (FP), is reported to be effective for the treatment of metastatic breast cancer (MBC). Although capecitabine, another oral FP, is widely accepted as the third-line chemotherapy for MBC, many patients treated with capecitabine suffer from hand-foot syndrome (HFS). HFS also affects survival in patients with metastatic colorectal and breast cancer. We retrospectively evaluated the potential association of HFS and survival in patients with MBC receiving S-1.
Methods: Forty-four patients with MBC treated with S-1 between 2005 and 2012 were analyzed. S-1 was administered at a standard dose of 50 mg/body twice daily for 4 weeks, followed by a 2-week interval. Partly, the drug was administered for 2 weeks, followed by a one-week interval. Trastuzumab (2 mg/kg/week) was added to the regimen for HER2-positive patients.
Results: The median follow-up period was 25.8 months and 12 patients (27.3%) developed HFS. Grade (G) 1 HFS was observed in 9 patients (20.5%) and G2 in 3 patients (6.8%). No G3/4 HFS was observed. Baseline demographic characteristics were comparable between the HFS and non-HFS patient groups. The HFS group showed a superior response rate (50.0% vs. 9.4%; P=0.0046), and improved median PFS (9.8 vs. 4.7 months; log-rank P=0.0446) and OS (51.5 vs. 17.5 months; logrank P=0.0196). In multivariate analysis, HFS is the only and independent prognostic factor (HR 2.93; 95% CI, 1.12 to 9.27; P=0.0269) of OS.
Conclusion: HFS observed in patients with S-1 not only correlates with an antitumor effect, but is also an independent prognostic factor.