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  • Title: Adjuvant chemotherapy for localised colon cancer. Fluorouracil + folinic acid for node-positive, non-metastatic disease.
    Journal: Prescrire Int; 2011 Feb; 20(113):46-9. PubMed ID: 21488594.
    Abstract:
    The standard treatment for colon cancer is surgical excision. Adjuvant chemotherapy is intended to reduce the risk of relapse, which is responsible for the death of nearly half of all patients treated surgically for localised disease. After surgery for stage III disease (node involvement without metastases), the 5-year survival rate is about 63% with adjuvant chemotherapy combining fluorouracil and folinic acid, versus 51% with placebo, a statistically significant difference. After surgery for stage II disease (tumour spread beyond the intestinal wall but no node involvement), a meta-analysis updated in 2008 showed no impact of adjuvant chemotherapy on the overall survival rate. Fluorouracil + folinic acid administration according to the de Gramont protocol is the standard adjuvant treatment. The addition of regional fluorouracil chemotherapy did not further improve outcome in a trial in 1501 patients with stage II or stage III disease. The fluorouracil precursors, capecitabine and tegafur, provide no advantages in terms of efficacy or tolerability. These oral drugs have not been compared with the de Gramont protocol. A trial comparing raltitrexed versus fluorouracil + folinic acid was stopped because of an excess of deaths in the raltitrexed arm. In two large trials, each including more than 2000 patients, the addition of oxaliplatin to the fluorouracil + folinic acid combination (Folfox 4 protocol) in patients with stage III disease appeared to slightly improve overall survival in patients under 65 years of age, but severe neuropathy, diarrhoea, nausea and vomiting were more frequent. In three trials in a total of more than 3000 patients with stage III disease, the addition of irinotecan did not improve the efficacy of the fluorouracil + folinic acid combination, while serious adverse effects were more frequent. No new drugs intended for the treatment of colon cancer have been introduced since 2006, but better evaluation of existing drugs means that patients with stage III colorectal cancer can now be offered a choice between standard intravenous fluorouracil and oral capecitabine or tegafur. Oxaliplatin adjunction is another option for patients under 65. The adverse effect profile is an important factor in the choice of treatment.
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