Improved regional selectivity of hepatic arterial bcnu with degradable microspheres

Abstract

Starch microspheres 40 μm in diameter, which are rapidly degraded by serum amylase, have been administered through hepatic arterial catheters to five patients with primary and metastatic liver cancer to determine whether (1) arterial blood flow through the liver could be temporarily blocked, and (2) such occlusion at the level of the arteriolar capillary bed would enhance regional uptake and catabolism and decrease systemic exposure to simultaneously administered hepatic arterial bischlorethylnitrosourea (BCNU). It was possible with 10 ml of microspheres (9 × 106 microspheres/ml) injected into the hepatic artery to transiently (for 15‐30 minutes) reduce hepatic flow by 80‐100% in the five patients. When BCNU (50 mg/m2 in one minute) was given with microspheres there was a 30‐90% reduction in systemic nitrosourea exposure and in peak levels. No myelosuppression was noted and hepatic toxicity consisted of acute pain due to BCNU and 1.5‐2.0 fold transient enzyme elevations. One patient with cholangiocarcinoma showed a partial response lasting three months; three patients had stable disease and one patient with colon carcinoma had progressive disease. Thus, this pilot study suggests that concurrent intra‐arterial microspheres and BCNU may have the potential to improve selective regional drug effect with marked diminution in systemic toxicity.

A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial

“…The duration of occlusion in the hepatic arteries by DSM is limited to 80 min [22]. Several studies of metastatic liver tumors indicate that intra-arterial therapy with DSM and an anticancer agent improves the therapeutic effects compared with therapy using an anticancer agent alone [22][23][24]. However, few studies have evaluated TAI using DSM in HCC patients [25][26][27].…”

Degradable Starch Microspheres versus Ethiodol and Doxorubicin in Transarterial Chemoembolization of Hepatocellular Carcinoma

“…With a half-life of approximately 40 minutes, the duration of arterial occlusion by DSMs is limited to a maximum of 80 minutes (8,9). After that, microspheres are degraded by serum α-amylase that is mainly produced by pancreatic acinous cells (10)(11)(12)(13). The reduced or halted blood flow increases in situ time and the tumor exposure, and thereby the efficacy of any coadministered drug (13,14).…”

Arteriovenous shunting in patients with colorectal liver metastases

“…There are two mechanisms of value. Firstly, cytotoxic drugs have been co-administered with biodegradable microspheres which temporarily slow hepatic arterial blood-flow in the tumourbearing liver and increase uptake of drug by the cells (Dakhil et al, 1982;Thom et al, 1989). Secondly, anti-cancer agents, including Adriamycin, mitomycin C, 5 fluorouracil, cis-platin and cytocidal radio-nuclides have been loaded into particles which act as controlled release vehicles in the target tissue Fujimoto et al, 1985;Okamoto et al, 1986;Herba et al, 1988).…”