A. Falcone et al., SURAMIN IN PATIENTS WITH METASTATIC COLORECTAL-CANCER PRETREATED WITHFLUOROPYRIMIDINE-BASED CHEMOTHERAPY - A PHASE-II STUDY, Cancer, 75(2), 1995, pp. 440-443
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.