Significant association between hand-foot syndrome and efficacy of capecitabine in patients with metastatic breast cancer.

Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is a promising treatment for colorectal, breast and gastric cancers, but often causes hand-foot syndrome (HFS), the most common dose-limiting toxicity. The current study was conducted to investigate the relationship between HFS and efficacy of capecitabine in 98 patients with metastatic breast cancer. Possible associations between HFS and efficacy endpoints, including time-to-treatment failure (TTF), tumor response in metastatic lesions and changes in tumor markers, were investigated retrospectively using electronic medical records. The TTF of group with HFS of grade 1 and ≥2 was significantly longer than that of group with no HFS, respectively (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.18-0.87 for group with grade 1; HR, 0.42, 95% CI, 0.19-0.90 for group with grade ≥2). Significantly higher disease control rates for the liver metastasis were observed in patients with HFS (grade 1 and greater) than in those without HFS (92.9 vs. 42.9%, p=0.009). Furthermore, prevention of increases in tumor marker levels (carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3) and National Cancer Center-Stomach-439 (NCC-ST439)) was evident in patients with HFS. This study clearly showed a significant correlation between HFS and some efficacy markers of capecitabine therapy in patients with metastatic breast cancer, and suggests that early dose adjustment based on severity of HFS might improve efficacy. Studies are needed to explore predictive biomarkers for HFS/efficacy, so that capecitabine therapy can be further tailored to patient response.
AuthorsYuichiro Azuma, Kojiro Hata, Kimie Sai, Ryoko Udagawa, Akihiro Hirakawa, Masahiro Tohkin, Yasuaki Ryushima, Yoshinori Makino, Nobuaki Yokote, Norifumi Morikawa, Yasuhiro Fujiwara, Yoshiro Saito, Hiroshi Yamamoto
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 35 Issue 5 Pg. 717-24 ( 2012) ISSN: 1347-5215 [Electronic] Japan
PMID22687407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Prodrugs
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil
  • Aged
  • Antimetabolites, Antineoplastic (adverse effects, therapeutic use)
  • Biomarkers, Tumor (blood)
  • Breast Neoplasms (blood, drug therapy, pathology)
  • Capecitabine
  • Confidence Intervals
  • Deoxycytidine (adverse effects, analogs & derivatives, therapeutic use)
  • Female
  • Fluorouracil (adverse effects, analogs & derivatives, therapeutic use)
  • Hand-Foot Syndrome (etiology)
  • Humans
  • Liver Neoplasms (blood, drug therapy, secondary)
  • Middle Aged
  • Prodrugs (adverse effects, therapeutic use)
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Outcome

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