Which endpoints should we use in evaluating the use of novel fluoropyrimidine regimens in colorectal cancer?

• Published in: British journal of cancer 2002-06, Vol.86 (11), p.1670-1676
• Main Authors: Twelves, C J, Cassidy, J
• Format: Article
• Language: English
• Subjects: Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Capecitabine; Chemotherapy; Clinical Trials, Phase III as Topic; Colorectal cancer; Colorectal Neoplasms - drug therapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Drug Resistance; Epidemiology; Fluorouracil - analogs & derivatives; Humans; Medical research; Medical sciences; Metastasis; Molecular Medicine; Oncology; Pharmacology. Drug treatments; Pyrimidines - administration & dosage; Pyrimidines - therapeutic use; Research Design; Response rates; Review; Safety; Schedules
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600341

Although significant advances have been made in the treatment of advanced/metastatic colorectal cancer, 5-fluorouracil (5-FU) still forms the basis of chemotherapy. Recently, new 5-FU schedules and novel fluoropyrimidines have been developed, but there are no trials directly comparing these regimens. The current review describes the mechanisms of action, pre-clinical and phase I/II studies of two oral fluoropyrimidine therapies, capecitabine and uracil with tegafur plus leucovorin. It also compares the phase III studies of these agents with those of the two most popular infusional 5-FU-based regimens: de Gramont and German AIO (The Association of Medical Oncology (AIO) of the German Cancer Society). Both oral and infusional regimens demonstrated similar survival to the Mayo Clinic regimen, a standard treatment for colorectal cancer. Therefore, other endpoints must be examined to decide optimum therapy, including response rates, time to disease progression, tolerability and patients' convenience. All four new therapies demonstrated superior safety profiles compared with the Mayo Clinic regimen. However the uracil with tegafur plus leucovorin regimen was associated with severe diarrhoea and capecitabine with hand–foot syndrome. Patients will not sacrifice efficacy for the convenience of oral therapy alone, therefore the fact that capecitabine achieved superior response rates and equivalent time to disease progression compared with the Mayo Clinic regimen, while uracil with tegafur plus leucovorin produced lower response rates and significantly inferior time to disease progression, is highly relevant in choosing treatment.