Temporary chemoembolization of colorectal liver metastases with degradable starch microspheres

Increasing drug delivery to the tumor should induce improved tumor response. To study this the effect of degradable starch microspheres (DSM) and mitomycin was evaluated in 11 patients with chemoembolization of colorectal liver metastases (CRLM) and previous floxuridine (FUDR) treatment. In 10 patients access to the hepatic artery was obtained either by infusaid pump or infusion chambers. Indications for chemoembolization were: Failure of continuous FUDR treatment (n = 7), biliary sclerosis (n = 2), incomplete liver perfusion (n = 2), extensive disease (n = 2). Preliminary observations showed a wide range of required DSM dose. Therefore each individual dose was determined by the use of digital subtraction angiography (DSA). Seventy-five percent of the DSM dosage, which induced reversed flow in the common hepatic artery, was selected for treatment. DSM was then administered four times every 2 hours/day/monthly. The last DSM doses were mixed with 10 mg mitomycin C. Observed response rates, controlled by chemotherapy (CT) and tumor markers, were: complete response 1/11; partial response 3/11; stable disease 2/11; progression 5/11. The median duration of response was 6.5 (range 3-21) months. DSM application induced redistribution of arterial flow towards previously unperfused portions of the liver. The required DSM doses decreased about 20-30% from the first to the last chemoembolization cycle. Although there was no systemic toxicity, embolization was associated with several local side effects. Moderate to heavy pain in spite of morphia and neuroleptics was experienced in 55% of all treatments. Some patients demonstrated an elevation in body temperature of up to 39 degrees C. Postembolization liver biopsies revealed more intense tumor necrosis associated with more severe hepato-toxicity than was seen with continuous FUDR treatment. It is concluded that the optimal sequence and dosage of mitomycin and DSM has to be further evaluated in prospective trials before clinical application.