New aspects in the palliative treatment of metastatic colorectal carcinoma

Background: Despite a decrease in both the incidence of colorectal carcinoma and the mortality due to this disease, it is still the second most common cause of death in the Western world. Refined surgery and adjuvant chemotherapy have not been able to prevent the frequent recurrence of colorectal cancer, often in a nonresectable state. In this palliative situation, which may already occur during initial presentation, the following treatment is indicated: best Supportive care and a differential and stepwise chemotherapy. Palliative chemotherapy retards the progression of cancer disease and improves Survival (from 6-9 months to 15-18 months). Chemotherapy Should already be started in asymptomatic patients, if cancer disease is progressive. Chemotherapy: 5-fluorouracil (5-FU) remains the key drug for palliative chemotherapy. Drug effects and side effects critically depend oil the mode of application and oil biomodulation (e.g. by folinic acid [leucovorin, LV]). Compared with the traditional bolus therapy of 5-FU/LV, we prefer infusional therapy for 24 hours because of its higher effectivity and fewer side effects. Further drugs that may be given in addition to or as ail alternative to 5-FU, are sodium folinate, raltitrexed and oral fluoropyrimidines (so-called prodrugs, e.g., capecitabine and tegafur-uracil [UFT]). These drugs are still under clinical investigation. Capecitabine, ill particular, appears to be a useful alternative for intravenous 5-FU therapy. When compared with the traditional 5-FU bolus therapy (Mayo regimen), capecitabine is at least equally effective, but has fewer side effects. Furthermore, it call be given orally. If treatment failure occurs under 5-FU, the application of oxaliplatin or irinotecan may be useful for second- and third-line therapy (partial remission rates of 10% or 13-15%). First-Line Therapie: Four randomized Phase-III studies demonstrate the effectiveness of additional therapy with oxaliplatin and irinotecan in combination with 5-FU for first-line chemotherapy of colorectal cancer. Triple therapy improves remission rates, quality of life and (shown only for irinotecan/ 5-FU/LV) survival rate, but causes more side effects and costs.