Evaluation of a new lipophilic prodrug 3', 5'-dioctanoyl-5-bromodeoxyuridine (BrdU-C8) suspended in Lipiodol as a radiosensitizer for the treatment of AH136B tumor.

The effect of anti-cancer treatment on the AH136B tumor was studied using external beam irradiation in combination with a new oil-soluble agent, 3', 5'-dioctanoyl-5-bromodeoxyuridine (BrdU-C8), a lipophilic prodrug of BrdU. BrdU-C8 was dissolved in an oily lymphographic agent, Lipiodol (BrdU-C8/Lipiodol). BrdU-C8/Lipiodol is selectively accumulated in the neovasculature of the tumor and gradually releases BrdU. The AH136B tumor cell, a transplantable rat ascites hepatoma cell line, was implanted in the dorsal foot of rats. In vivo labeling index (L.I.) of the tumor cells after the intraarterial infusion of BrdU-C8/Lipiodol was significantly increased compared to the L.I. observed after intraarterial or intravenous infusion of BrdU. In addition, X-ray irradiation in combination with intraarterial infusion of BrdU-C8/Lipiodol significantly inhibited the tumor growth, indicating the increased radiosensitizing effect.

A new approach to chemoembolization for unresectable hepatocellular carcinoma using aclarubicin microspheres in combination with cisplatin suspended in iodized oil.

Sixty-six consecutive patients with unresectable hepatocellular carcinoma (HCC) were treated with transcatheter arterial chemoembolization (TACE) using aclarubicin microspheres (ACRms) in combination with cisplatin suspended in iodized oil (Lipiodol, Laboratoire Guerbert, Paris, France) (CSL). The stages of the disease were as follows: Stage I (n = 1), Stage II (n = 10), Stage III (n = 26), and Stage IV (n = 29). The effectiveness of TACE was assessed by comparing ACRms with CSL with ACRms without CSL. Of 66 patients treated with ACRms and CSL, 62 (93.9%) could be examined for response. According to response criteria, there were 31 (50.0%) partial responses and 17 (27.4%) minor responses. In 13 cases (21.0%) there was no change and in 1 case (1.6%) there was progressive disease. The cumulative survival rate was 80.7% at 1 year, 64.2% at 2 years, and 50.6% at 3 years. The rates were significantly higher than those of the group treated with ACRms. Eleven patients in the ACRms and CSL group experienced clinical complications: cholecystitis (4.5%), pancreatitis (3.0%), liver abscess (3.0%), hepatic failure (3.0%), gastrointestinal bleeding (1.5%), and renal failure (1.5%). No lethal side effects related to the therapy were observed. TACE using ACRms in combination with CSL prolongs the survival of patients with unresectable HCC.