Evaluation of the Use of Capecitabine for the Treatment and Prevention of Actinic Keratoses, Squamous Cell Carcinoma, and Basal Cell Carcinoma: A Systematic Review

Key PointsQuestionWhat evidence exists for the use of capecitabine for the treatment and prevention of precancerous and cancerous skin lesions? FindingsIn this systematic review of 16 publications, patients receiving capecitabine chemotherapy for breast and colorectal cancer experienced inflammation of preexisting actinic keratoses. Low-dose capecitabine was associated with a reduced incidence of squamous cell carcinomas in high-risk patients, including solid organ transplant recipients; however, adverse effects may limit its use. MeaningThe findings suggest that capecitabine chemoprevention may be considered in high-risk patients, such as solid organ transplant recipients, particularly those with a history of multiple squamous cell carcinomas, although additional study is warranted to determine optimal patient selection and dosing as well as long-term safety and efficacy. ImportanceCertain patient groups, such as solid organ transplant recipients (SOTRs), have a significantly increased risk of developing skin cancers. The chemotherapeutic drug capecitabine has been used off label as a chemopreventive modality to suppress the development of precancerous skin lesions and squamous cell carcinomas (SCCs). ObjectiveTo systematically review published studies on the use of capecitabine for the treatment and prevention of precancerous and cancerous skin lesions, with a focus on cutaneous SCC. Evidence ReviewFor this systematic review, a literature search was performed using the PubMed and Embase databases in December 2019 for all articles published between January 1, 1998, and December 31, 2019, using the search term capecitabine paired with each of the following terms: actinic keratosis, actinic keratoses, squamous cell carcinoma, and basal cell carcinoma. Articles on the use of capecitabine for the treatment and prevention of actinic keratoses (AKs), SCCs, and basal cell carcinomas (BCCs) were selected for inclusion. FindingsSixteen publications met the criteria for inclusion, with 8 case reports describing the inflammation of AKs in patients with solid organ cancer treated with capecitabine (2 patients with breast cancer and 6 patients with colorectal cancer). One case report and 1 case series of 4 patients investigated the use of capecitabine for the treatment of advanced or widespread cutaneous SCCs. A total of 6 publications (3 case reports and 3 case series) described the use of capecitabine to prevent development of SCCs in SOTRs. Of these case series, 2 studies found a significant reduction in SCC incidence rate during treatment with capecitabine compared with before treatment. Adverse effects, such as fatigue, nausea, vomiting, diarrhea, elevated creatinine level, hand-foot syndrome, hyperuricemia, weight loss, anemia, and cardiomyopathy, limited the duration of chemoprevention in several patients. Conclusions and RelevanceCapecitabine treatment may be associated with a decrease in the incidence of SCCs in SOTRs. Capecitabine treatment may also be associated with a decrease in AK and BCC incidence. However, practitioners must weigh this benefit against the risk of adverse effects for each patient individually. Further investigation with a prospective clinical trial is warranted. This systematic review examines the evidence of the use of capecitabine for the treatment and prevention of precancerous and cancerous skin lesions.