First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous5-fluorouracil/leucovorin

Abstract

Capecitabine is at least as effective, better tolerated and more convenient than i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer. Analysis of data from two large phase III trials demonstrates that efficacy is not compromised in patients requiring a dose reduction for adverse events. The phase III data and an additional pharmacokinetic study support a lower starting dose in patients with moderate renal impairment at baseline (calculated creatinine clearance 30-50 ml/min) and a contra-indication in patients with severely impaired creatinine clearance at baseline (<30 ml/min). For patients with normal or mildly impaired renal function at baseline, the standard starting dose is well tolerated. The incidence and severity of adverse events in patients with moderate renal impairment at baseline who were treated with 5-FU/leucovorin was more pronounced, indicating that capecitabine provides a better-tolerated alternative.

Therapeutic drug monitoring of 5-fluorouracil

“…Over the past 10 years, there has been an increasing use of capecitabine monotherapy and capecitabine-based combination regimens in the treatment of mCRC, which has been due, in large part, to the convenience and increased patient preferences for oral chemotherapy [50–54]. Randomized studies have shown that capecitabine-based treatments are associated with equal clinical efficacy and reduced toxicities when compared to infusional 5-FU regimens [50–54].…”

“…Randomized studies have shown that capecitabine-based treatments are associated with equal clinical efficacy and reduced toxicities when compared to infusional 5-FU regimens [50–54]. Finally, several pharmacoeconomic studies have demonstrated that capecitabine-based chemotherapy is associated with significant cost savings when compared to infusional 5-FU chemotherapy, and these economic benefits are seen for the adjuvant therapy setting as well as for the treatment of metastatic disease [55–59].…”

Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

“…This likely reflects the variable metabolism of capecitabine-dose adjustment may functionally adjust exposure to biologically appropriate doses. Standard recommendations in the capecitabine package insert [20] are identical to those in the aforementioned trial and will be followed; these are recapitulated in table 4. Table 5 provides suggestion on dosereductions for specific toxicities.…”

“…The tablets are supplied as biconvex, oblong film-coated tablets. Each tablet is light peach colored tablet contains 150mg of capecitabine and each peach-colored tablet contains 500mg [20].…”

“…6.4 Slurry preparation of capectabine Capecitabine tablets are supplied as immediate-release, film-coated tablets and are water soluble [20]. AUC of whole-pill and crushed capecitabine has been found to be bio-equivalent by AUC0-6 [22].…”