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Management of Metastatic Colorectal Cancer

Defining the Role of Capecitabine

  • Drugs in Disease Management
  • Published:
Disease Management & Health Outcomes

Abstract

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®), 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.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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  1. Adis International Inc., 770 Township Line Road, Suite 300, Yardley, Pennsylvania, PA 19067, USA

    Lynda R. Wiseman & Katherine A. Lyseng-Williamson

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Correspondence to Katherine A. Lyseng-Williamson.

Additional information

Various sections of the manuscript reviewed by: M.M. Borner, Institute of Medical Oncology, Inselspital, Bern, Switzerland; K. Bujko, Department of Radiotherapy, The Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland; T. Conroy, Department of Medical Oncology, Centre Alexis Vautrin, Nancy, France; A.F. Grothey, Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA; F.G.A. Jansman, Department of Clinical Pharmacy, Isala Klinieken, Zwolle, The Netherlands; M. Malet-Martino, Groupe de RMN Biomedicale, Laboratoire des IMRCP, Universite Paul Sabatier, Toulouse, France; J.J. McKendrick, Department of Hematology and Medical Oncology, Box Hill Hospital, Melbourne, Australia; W. Scheithauer, Department of Internal Medicine, University Medical School, Vienna, Austria; P. Schöffski, Department of Clinical Oncology, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.

Data Selection

Sources: Medical literature published in any language since 1980 on drug-name, identified using Medline, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: Medline search terms were ‘colorectal cancer’ or ‘colorectal neoplasms’ and (‘guidelines’ or ‘decision-making’ or ‘health-policy’ or ‘managed-care-programmes’ or ‘epidemiology’ or ‘outcome-assessment-health-care’ or ‘clinical-protocols’ or ‘guideline in pt’ or ‘polic* in ti’ or ‘expert panel’ or ‘utilization review’ or ‘algorithms’ or ‘disease management’ or ‘quality of life’), or ‘capecitabine’ and ‘review in pt’. AdisBase search terms were ‘colorectal cancer’ and (‘guideline’ or ‘guideline-utilisation’ or ‘practice-guideline’ or ‘disease-management-programmes’ or ‘treatment-algorithms’ or ‘reviews-on-treatment’ or ‘drug-evaluations’ or ‘epidemiology’ or ‘cost-of-illness’ or ‘pathogenesis’), or ‘capecitabine’ and (‘review’ or ‘clinical-study’). Searches were last updated 2005 February 14.

Selection: Studies in patients with colorectal cancer who received capecitabine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic, pharmacoeconomic and epidemiological data are also included.

Index terms: Capecitabine, colorectal cancer, disease management, review on treatment.

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Wiseman, L.R., Lyseng-Williamson, K.A. Management of Metastatic Colorectal Cancer. Dis-Manage-Health-Outcomes 13, 137–149 (2005). https://doi.org/10.2165/00115677-200513020-00007

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