A MULTISTEP THERAPY WITH SUBCUTANEOUS LOW-DOSE RECOMBINANT INTERLEUKIN-2, 5-FLUOROURACIL AND LEUCOVORIN PROLONGS THE RESPONSE OF METASTATICCOLORECTAL-CANCER PATIENTS - A PILOT-STUDY

Data from 12 metastatic colorectal cancer patients who were submitted to a pilot study with a multistep subcutaneous (sc) low dose recombina nt interleukin-2 (rIL-2), 5-fluorouracil (5-FU) and leucovorin (LV) ad ministration were compared with those from 13 historical controls who were comparable for the major prognostic indices. All 12 patients in t he pilot study were subjected initially to six to eight courses of 5-F U-LV by endovenous (ev) bolus consistent with the Machover schedule al ternating with 6 weeks of rIL-2 cycles. At the progression of metastat ic disease, the patients were given 500 mg/m(2) per day of 5-FU by con tinuous infusion (ci) for 5 days every 4 weeks and in case of further progression, 2 600 mg/m(2) of 5-FU by 24-h ci once a week for 6 weeks. The control patients were treated with 5-FU-LV by the Machover schedu le until progression and then observed. As yet, two patients in the pi lot study and three control patients are currently alive. In the pilot study, the patients' response rate (CR + PR) and overall response rat e (CR + PR + SD) were much higher than in the controls (50 vs 23% and 92 vs 54%, respectively). Time duration of response and survival from primary surgery were more prolonged in the pilot study than in the his torical control, although not significantly (10.5 vs 6 and 41.5 vs 29 months, respectively). Time from starting therapy to progression and s urvival from relapse were significantly in favour of the pilot study ( 11.5 vs 4 and 31 vs 13.5 months; P < 0.01 and P < 0.05 unpaired t-test , respectively). Low dose sc rIL-2 cycles were well tolerated and no i nterruption occurred. In the pilot study sporadic grade 3 toxicity (di arrhoea or leucopenia) was responsible for the reduction of 5-FU doses to 80% of the previous infusion, but no treatment was postponed. In c onclusion, these preliminary data suggest the opportunity to Initiate large prospective randomized trials using a multistep therapy with rIL -2, 5-FU ci at conventional and at high dose in metastatic colorectal cancer. (C) 1998 Elsevier, Paris.