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Capecitabine in the management of colorectal cancer

By Bradford R Hirsch and S Yousuf Zafar


5-Fluorouracil has been a mainstay in the treatment of colorectal cancer for nearly five decades; however, the use of oral formulations of the medication has been gaining increasing traction since capecitabine was approved for use in adjuvant settings by the US Food and Drug Administration in 2005. The use of capecitabine has since spread to a number of off-label indications, including the treatment of advanced or metastatic colorectal cancer and the neoadjuvant treatment of rectal cancer. In light of increasing utilization, it is critical that clinicians have a firm understanding of the literature supporting capecitabine across various settings as well as the attributes of the drug, such as its dosing recommendations, side-effect profile, and use in the elderly. The purpose of this review is to synthesize the literature in a fashion that can be used to help guide decisions. In a setting of increasing focus on cost, the pharmacoeconomic literature is also briefly reviewed

Topics: Review
Publisher: Dove Medical Press
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Provided by: PubMed Central

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  1. (1999). A human capecitabine excretion balance and pharmacokinetic study after administration of a single oral dose of 14C-labelled drug. Invest New Drugs.
  2. A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.
  3. (2006). A randomised crossover trial comparing patient preference for oral capecitabine and 5-fluorouracil/leucovorin regimens in patients with advanced colorectal cancer. Ann Oncol.
  4. AIO Colorectal Study Group. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group.
  5. Biomodulation of 5-fluorouracil by interferonalpha in human renal carcinoma cells: relationship to the expression of thymidine phosphorylase.
  6. (2010). Cancer Network. The NCCN Clinical Practice Guidelines in Oncology: Colon Cancer (Version 2.2011). Available from: Accessed
  7. (2010). Cancer Network. The NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer (Version 2.2011). Available from: Accessed
  8. (2010). Cancer statistics,
  9. (2009). Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo-)adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): safety results of a randomized, phase III trial [abstract 4014]. J Clin Oncol.
  10. Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer.
  11. Capecitabine as adjuvant treatment for stage III colon cancer.
  12. Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an oncopaz cooperative group study.
  13. Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study.
  14. (2006). Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol.
  15. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study.
  16. (2010). Capecitabine-based chemotherapy for metastatic colorectal cancer. J Cancer Res Clin Oncol.
  17. (2001). Capecitabine: a novel agent for the treatment of solid tumors. Anticancer Drugs.
  18. Capecitabine: a review. Clin Ther.
  19. (2009). Capecitabine: have we got the dose right? Nat Clin Pract Oncol.
  20. Clinical pharmacokinetics of capecitabine.
  21. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study.
  22. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2.
  23. (2006). Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study.
  24. Cost-effectiveness analysis of XELOX for metastatic colorectal cancer based on the NO16966 and NO16967 trials.
  25. Costs associated with complications are lower with capecitabine than with 5-fluorouracil in patients with colorectal cancer.
  26. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue.
  27. (1998). Effect of food on the pharmacokinetics of capecitabine and its metabolites following oral administration in cancer patients. Clin Cancer Res.
  28. (2007). Efficacy and safety findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs infusional 5-FU/LV + O (FOLFOX-6) for metastatic colorectal cancer (MCRC) [abstract 4029]. J Clin Oncol.
  29. Efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-FU/LV for stage III colon cancer (NO16968): no impact of age on disease-free survival (DFS) [abstract 284].
  30. German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer.
  31. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts.
  32. Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5′-deoxy-5-fluorouridine by cyclophosphamide in mammary tumor models.
  33. (2008). Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol.
  34. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer.
  35. Neoadjuvant bevacizumab, capecitabine, and radiotherapy in locally advanced rectal cancer: interim results of a phase II CRAB trial [abstract e14006].
  36. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial.
  37. Patient preferences for oral versus intravenous palliative chemotherapy.
  38. Patients with locally advanced and metastatic colorectal cancer treated with capecitabine versus 5-fluorouracil as monotherapy or combination therapy with oxaliplatin: a cost comparison.
  39. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes’ C colon cancer: the X-ACT trial.
  40. (2003). Pharmacokinetics of capecitabine (Xeloda) in Japanese and Caucasian patients with breast cancer. Cancer Chemother Pharmacol.
  41. Phase I and pharmacologic study of intermittent twice-daily oral therapy with capecitabine in patients with advanced and/or metastatic cancer.
  42. Phase I–II trial of cetuximab, capecitabine, oxaliplatin, and radiotherapy as preoperative treatment in rectal cancer.
  43. (2007). Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer. Ann Oncol.
  44. Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer.
  45. Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer.
  46. Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study.
  47. Potential regional differences for the tolerability profiles of fluoropyrimidines.
  48. (2000). Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol.
  49. (1992). Preliminary evidence that incorporation of 5-fluorouracil into RNA correlates with antitumor response. Cancer Invest.
  50. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer.
  51. Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in locally advanced rectal cancer.
  52. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in firstline treatment of metastatic colorectal cancer: results from the BICC-C study.
  53. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study.
  54. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial.
  55. Severe sequence-specific toxicity when capecitabine is given after fluorouracil and leucovorin.
  56. The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer: how successful have we been? Ann Oncol.
  57. (2004). The X-Act Study Group. Safety of capecitabine (X) compared to fluorouracil/leucovorin (5-FU/LV) for the adjuvant treatment of elderly colon cancer patients (pts) [abstract 3737]. J Clin Oncol.
  58. (2010). Update 2010. Roche provides results on Avastin in adjuvant colon cancer. Available from: ir_update/inv-update-2010-09-18b.htm. Accessed
  59. (1981). Utilization of 5-fluoro-2′-deoxyuridine triphosphate and 5-fluoro-2′-deoxycytidine triphosphate in DNA synthesis by DNA polymerases alpha and beta from calf thymus. Cancer Res.
  60. (1999). X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res.
  61. Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study.