SURAMIN IN PATIENTS WITH METASTATIC COLORECTAL-CANCER PRETREATED WITHFLUOROPYRIMIDINE-BASED CHEMOTHERAPY - A PHASE-II STUDY

Background. The results of conventional chemotherapy in metastatic col orectal cancer are discouraging, making it a logical target for new tr eatment approaches a necessary consideration. Suramin is a polysulfona ted naphthylurea that binds to several cellular growth factors and has in vitro activity against human colorectal cancer cells. Therefore, t his Phase II study of patients with metastatic colorectal cancer was c onducted to evaluate its clinical activity. Methods. Suramin was admin istered as a 6-day continuous infusion every week for 8 consecutive we eks by using a computer-assisted dosing of Bayesan pharmacokinetics to maintain suramin plasma concentrations of 200-250 mu g/ml. Twenty pat ients with metastatic colorectal cancer who were not responsive or in progression within 6 months after completing fluoropyrimidine-based ch emotherapy entered the study. Results. Toxicities included mostly Grad e 1 and 2 fatigue, nausea and vomiting, peripheral neurotoxicity, crea tinine elevation, and proteinuria. No objective responses were observe d, but three of three patients who received 5-fluorouracil plus folini c acid after suramin achieved a partial response. Conclusions. These r esults indicate that suramin is inactive in patients with metastatic c olorectal cancer pretreated with fluoropyrimidines. Pretreatment with suramin may have changed the biology of the tumor, sensitizing it to f luoropyrimidines. Studies to investigate this possibility are in progr ess.