SEQUENTIAL BIOCHEMOTHERAPY FOR METASTATIC COLORECTAL-CANCER USING, FLUOROURACIL, FOLINIC ACID, THYMOPENTIN AND INTERLEUKIN-2 - CLINICAL ANDIMMUNOLOGICAL EFFECTS

Background: A phase II study was performed to evaluate the clinical an d immunological effects of a regimen of fluorouracil (5-FU) and folini c acid (FA) combined with thymopentin (TP-5) and interleukin-2 (IL-2) in the treatment of patients with metastatic colorectal cancer. Patien ts and methods: Forty-five evaluable patients with measurable colorect al cancer and no prior therapy for metastatic disease were treated wit h 5-FU 400 mg/m(2)/d and FA 200 mg/m(2)/d i.v. on days 1-5, TP-5 50 mg s.c. on days 8-11, and IL-2 9 MLT/m(2) s.c. twice daily on days 12-16 . Cycles were repeated at 4-week intervals if toxicity had resolved. I mmunological changes were evaluated in 13 patients and compared with a well matched series of 13 patients treated with the same regimen with out TP-5. Results: Two complete responses and 17 partial responses wer e seen (42%; 95% confidence interval, 28% to 56%). Fifteen patients (3 3%) had stable disease. The median time to progression was 8.5 months and the median survival 13 months. Treatment was reasonably well toler ated, and there was no overlapping toxicity or interference between ch emotherapy and biotherapy. Hematological and immunological changes dur ing treatment were qualitatively similar to those expected with IL-2+/ -chemotherapy. Quantitatively, significant changes (higher levels of I L-2, CD25 and IFN-gamma, and lower levels of sIL-2R) were observed in patients given TP-5. Conclusion. The combination of 5-FU + FA and TP-5 + IL-2 is effective in advanced colorectal cancer with accept able to xicity. Immunological data suggest that TP-5 may modulate the action o f IL-2 in the clinical setting. However, improved treatment approaches are needed, and the interactions between thymic hormones and cytokine s should be further explored.