Management of metastatic colorectal cancer defining the role of capecitabine

Colorectal cancer (CRC), one of the most common cancers, is associated with significant morbidity, mortality, and medical costs. Treatment options in metastatic CRC are largely palliative, and aim to provide symptom relief, improve health-related quality of life, and prolong survival. Chemotherapy is the mainstay of treatment for metastatic disease. Fluorouracil/leucovorin with or without oxaliplatin or irinotecan is the most widely used regimen. These agents are administered intravenously (by bolus or infusion), thereby causing significant inconvenience to patients. Capecitabine (Xeloda (R)), an oral fluoropyrimidine, is currently recommended as single-agent first-line treatment in patients with metastatic CRC in whom fluoropyrimidine monotherapy is the preferred option. As first-line monotherapy, capecitabine is as least as clinically effective as bolus fluorouracil/leucovorin in terms of time to disease progression, time to treatment failure, and overall survival, but achieves significantly higher response rates and has the added advantage of oral administration. In addition, capecitabine has improved tolerability with a significantly lower incidence of diarrhea, stomatitis, nausea, and alopecia than fluorouracil/leucovorin. The lower incidence of grade 3 or 4 neutropenia with capecitabine results in significantly less neutropenic fever/sepsis and, consequently, fewer hospitalizations. The significantly higher incidence of hand-and-foot syndrome with capecitabine rarely necessitates hospitalization. Measures of resource utilization found patients treated with capecitabine had fewer hospital visits for drug administration, fewer days in hospital for management of treatment-related adverse events, and required less expensive drug therapy for the management of adverse events than fluorouracil/leucovorin recipients. In cost-minimization studies in various countries, these benefits translated into cost savings with capecitabine relative to fluorouracil/leucovorin. Clinical trials have shown combination therapy with capecitabine and either irinotecan or oxaliplatin to be effective and well tolerated. Capecitabine appears to be an acceptable alternative to fluorouracil/leucovorin in combination therapy. Moreover, one economic analysis predicted that capecitabine plus oxaliplatin will result in cost savings compared with fluorouracil/leucovorin plus oxaliplatin. In conclusion, oral capecitabine offers an effective, but more convenient, alternative to bolus fluorouracil/leucovorin in the first-line treatment of patients with metastatic CRC. The improved tolerability and cost savings of capecitabine relative to fluorouracil/leucovorin support the use of capecitabine when treatment with fluoropyrimidine therapy alone is the preferred option. Results of further phase III trials of capectabine plus either irinotecan or oxaliplatin are eagerly awaited to determine if replacing fluorouracil/leucovorin with capecitabine in combination therapy will result in further improvements in convenience, tolerability, and, ultimately, cost savings for patients and payors in the metastatic CRC setting.