Capecitabine

Additional information

Capecitabine is an orally administered precursor of the cytotoxic 5-fluorouracil. It is indicated for the treatment of metastatic colorectal cancer, advanced gastric cancer, advanced breast cancer, and as an adjuvant therapy for patients undergoing surgery for stage III colon cancer [1].

Pharmacokinetics and dosing

A pharmacokinetic study (16 men, 9 women) showed sex differences in effect only for AUC and Cmax of intact drug and for Cmax of one of its metabolites (FBAL), which were higher in women than in men. However, this effect has no clinical significance as both intact drug and FBAL lack intrinsic antiproliferative activity [2]. Furthermore, a population analysis of pooled data from two large controlled studies in patients with metastatic colorectal cancer treated with capecitabine (303 men, 202 women) indicated that patient’s sex and race have no influence on the pharmacokinetics of capecitabine and its metabolites (5’­DFUR, 5-FU and FBAL) [1]. No difference in dosing between men and women is recommended by the pharmaceutical company [1].

Effects

Sex differences on in-vitro colonic motility after chemo- and radiotherapy have been seen. In an in-vitro study, segments of sigmoid colon were obtained from controls operated on colorectal resection for rectal cancer (8 men, 7 women), and patients with colorectal resection for rectal cancer who also received treatment with capecitabine and radiotherapy (7 men, 7 women) [3]. The samples were exposed to increasing carbachol or histamine concentrations to obtain concentration-response curves. In male samples, carbachol and histamine caused concentration-dependent contractions in the control and treated group. However, in female samples, the response to both carbachol and histamine was not different between the two groups and the maximal responses to carbachol were greater in the samples from the control group than from the treated group. Electrically evoked contractions were more pronounced in male samples, especially in the treated group [3]. 

Adverse effects

The results of a meta-analysis of 14 clinical trials with data from over 4700 patients treated with capecitabine showed that female sex was associated with an increased risk of developing hand-food syndrome and diarrhea, and a decreased risk of developing neutropenia [1].

A retrospective study of colorectal cancer patients (163 men, 136 women) showed that women experience a higher dose-limiting toxicity (DLT) incidence than men (67.7% vs. 52.2%) when given adjuvant capecitabine dosed according to body surface area [4]. The most commonly reported DLT were palmar-plantar erythrodysesthesia (44.9% in women vs. 35.2% in men) and diarrhea (30.1% in women vs. 17.9% in men). Subsequently, women required more dose reductions than men. However, a similar number of men and women required discontinuation of therapy [4].

Another study showed that both female sex and pretreatment anemia were associated with hematological toxicities in colorectal cancer patients treated with capecitabine [5].

Reproductive health issues

Capecitabine can cause fetal harm and is therefore contraindicated during pregnancy. It is recommended that women of childbearing potential (and/or their partner) treated with capecitabine use effective contraception during and for six months after the treatment. For men, effective contraception is recommended during and for three months after the treatment [1]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects(in Swedish, Janusmed fosterpåverkan).