Adjuvant therapy in colorectal cancer – studies of the FOGT group

The FOGT (Study Group for GI-Oncology) was formed among clinicians and scientists with the aim of testing innovative scientific concepts in gastrointestinal tumors, especially colorectal cancers, within controlled clinical studies. In the FOGT-1 trial (n=813stage III or II(T4N0) colon cancer patients) the effect on recurrence-free and overall survivalwas tested by an adjuvant chemotherapy protocol with double-modulation of 5-fluorouracil (5-FU) and levamisole (LEV) with either folinic acid (FA) or interferon-alpha (IFNa) in a three arm randomized trial within 60 German cancer centers. In parallel, in the FOGT-2 trial stage II or III rectal cancer patients (n = 796 pts.) were treated with additional postoperative radiochemotherapy (50,4 Gy). The most effective arm of these trials was tested as control arm versus a 5-FU/FA/ irinotecan (FOLFIRI) protocol in the two-arm FOGT-4 trial (n = 281stage III or II(T4N0) colon cancer pts.) for adjuvant therapy in colon cancer. In the FOGT-1 trial, we found a 11% overall survival (OAS) benefit in patients who were treated for one year adjuvantly with 5-FU plus FA (77% OAS), compared to treatment with either 5-FU or 5-FU plus interferonalpha (each 66% OAS). This effect was statistically significant for colon cancer patients (FOGT-1), but not for rectal cancer patients (FOGT-2). In rectal cancer, the 5-FU plus FA arm showed this effect with a 12% survival benefit only in the stage II subgroup. The FA modulation of 5-FU was safe and cost-effective. The modulation with IFNa was less effective and caused more toxicity, mainly diarrhea in rectal cancer patients. When the 5FU/FA protocol was slightly modulated (treatment for 6 months, no LEV) and compared to the FOLFIRI protocol (FOGT-4), survival and toxicity in the 5FU/FA arm was similar to the toxicity observed in the earlier studies, and the FOLFIRI arm was significantly more toxic (40% vs. 14% grade III/IV toxicity) without any benefit in recurrence rates (25% vs. 23% local/systemic recurrence) or survival. The FOGT-4 study confirms three other studies that – in contrast to palliative treatment protocols – did not find any benefit for the role of irinotecan in the adjuvant treatment of colon cancer. In conclusion, by conducting the three FOGT-studies with more than 1800 patients, we identified a safe and effective treatment protocol for adjuvant therapy in colon cancer, consisting of infusional 5-fluorouracil and folinic acid, given for at least six months, and well combinable with additional postoperative radiotherapy. This protocol was not improved by addition of irinotecan in colon cancer patients.