BIOMODULATION WITH SEQUENTIAL INTRAVENOUS IFN-ALPHA-2B AND 5-FLUOROURACIL AS 2ND-LINE TREATMENT IN PATIENTS WITH ADVANCED COLORECTAL-CANCER

A phase II trial was carried out by the Grupo Oncologico Cooperative d el Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interfe ron (IFN)-alpha 2b in patients with advanced colorectal carcinoma refr actory to previous therapy with 5-FU modulated by methotrexate (MTX) o r leucovorin (LV) or both. Between January 1993 and October 1995, 34 p atients were entered on the study. The treatment was IFN-alpha 2b 5 x 10(6)/m(2) IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m(2) i.v. bolus injection. Courses were repeated weekly until obse rvation of progressive disease or severe toxicity. One patient could n ot be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%), No patient achieve d a complete response. Two patients had partial responses (6%), No cha nge was recorded in 14 patients (41%), and progressive disease occurre d in 17 (52%), The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limit s. The main side effects were mucositis and diarrhea, Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The m ost frequent toxic effects attributable to IFN-alpha 2b were mild fati gue and fever. In conclusion, second-line therapy with i.v. IFN-alpha 2b preceding 5-FU has shown an interesting profile of activity in a pa tient population with clearly unfavorable characteristics. From this p erspective, further appropriately designed studies are needed to ident ify the greatest potential of IFN-alpha 2b as a modulator of 5-FU.