SUBCUTANEOUS LOW-DOSE INTERLEUKIN-2 AND INTRAVENOUS 5-FLUOROURACIL PLUS HIGH-DOSE LEVOFOLINIC ACID AS SALVAGE TREATMENT FOR METASTATIC COLORECTAL-CARCINOMA

Thirty-three consecutive patients with recurrent and/or metastatic col orectal carcinoma (CRC) refractory to previous chemotherapy have been treated with levofolinic acid (I-FA) 100 mg/m(2) i.v. over 1 h infusio n followed by 5-fluorouracil (5-FU) 600 mg/m(2) i.v. bolus every week for 6 weeks followed by a 2 week interval. Patients also received rIL- 2 s.c. at 3 MU daily from day 1 to day 5 of each week for at least fou r consecutive weeks per cycle, Enrolled patients were divided in two g roups: (i) group 1 including patients with progressive tumor refractor y to chemotherapy with 1-FA+5-FU given for metastatic disease and (ii) group 2 consisting of patients with diagnosis of metastatic disease w ithin 3 months from the completion of adjuvant chemotherapy with 5-FUlevamisole (LEV) after primary surgery. No objective response was obse rved in the group of 11 patients with CRC resistant to previous I-FA 5-FU, thus no further patient with progressive disease after 1-FA + 5 -FU was included in the trial, In the group of patients pretreated wit h 5-FU + LEV, four patients experienced a PR with a mean duration of 7 .3 months (range greater than or equal to 4.0-8.6) for an overall resp onse rate of 18% (95% CI 12-26%), A stabilization of disease was obser ved in five cases (23%) with a mean duration of greater than or equal to 5.6 months (range greater than or equal to 2.0-7.0), The remaining 13 patients progressed, No complete responses were achieved, The mean overall survival was greater than or equal to 9.5 months (range greate r than or equal to 2.0-14.0). Toxicity was generally mild. This study demonstrates that the combination of s.c. rIL-2 and intravenous 5-FU I-FA on a weekly schedule may be safely given to patients with metast atic CRC on an outpatients basis. The addition of low-dose rIL-2 does not modify the toxicity profile of 5-FU + 1-FA, even if IL-2-related s ide-effects such as systemic symptoms or cardiac abnormalities are to be expected. The clinical activity of the combination is not good, at least in terms of response rate, even if the duration of partial respo nses may suggest to test rIL-2 in a prospective study with response du ration and overall survival as the final endpoints.