A basic study superselective transcatheter arterial chemotherapy and chemoembolization (III) – a new drug carrier: liposome -CDDP- *
Purpose The purpose of this sludy was to clarify the usefulness of liposome-CDDP emulsion in canccr treatment when administered with or without imipenem cilastatin sodium suspension (IPM/CS) by the superselectivc transcatheter arterial chemotherapy method. Materials and Methods VX2 tumors about of 20 mm in diameter, which had been inoculated into rabbit auricles 14 days earlier were used in this experiment. The platinum concentration was adjusted to 0.25 mg/kg with a saline solution and the solution was mingled with liposome until it becamc a CDDP-liposomc emulsion. Then the emulsion was injected into an auricular artery of the tumor bearing rabbit by the superselective transcathctcr arterial chemotherapy method (STAC/Lip) or the chemomicroembolization method (STACME/Lip). In the latter case, the emulsion was injected secondary to the initial injection of IPM/CS. In several tissues, such as tumor and kidney tissues and blood platinum concentrations were assayed by atomic absorption spectroscopy at 0, 5, and 15 min after the injection of platinum. The anti-tumor effect of STAC/Lip and STACME/Lip was compared by measuring the growth rate of the tumors of about 10 mm in diameter in three rabbits on the fifth day of the treatment. The rabbits were sacrificed thereafter to measure platinum concentration in the tissues and blood platinum concentrations. Results Regarding the elapsed time after CDDP administration, the platinum concentration of the tumors in the STACME/Lip group showed a statistically significant difference when compared with that of the STAC/Lip group assayed at 5 min. but the difference was not significant between the groups when assayed at 0 and 15 min. Comparison of the platinum concentrations in a previously reported study7) (expressed as STAC/Cis and STACME/Cis, hereafter) with those in present study showed a statistically significant difference. In short, there was a higher tumor platinum concentration in the STACME/Lip group at 15 min. than in STAC/Cis and STACME/ Cis groups after the same length of time. The growth rates of the tumors of the STAC/Lip and STACME/Lip groups measured at the fifth days after the treatment were 88.0 ± 23.8% and 22.9 ±8.8%, respectively, and the difference between the two groups was statistically significant (p<0.05). A comparison of the growth rates of the tumors in STAC/Lip and STACME/Lip groups with that in STAC/Cis and non-therapy control groups indicated that tumor growth was more strongly suppressed in the former than in the latter, and the difference was statistically significant. The platinum concentrations of the tumors in the STAC/Lip and STACME/Lip groups measured at the fifth days after treatment were 0.99 ± 0.22 μg/g and 1.27 ± 0.14 μg/g, respective-ly. These levels were significantly higher than those in the STAC/Cis and STACME/Cis groups measured on Fifth day. Conclusion Liposome-CDDP emulsion administered with or without IPM/CS was proved to be valuable in attaining high tissue platinum concentration levels and a suppression effect on tumor growth. (Accepted on October 26, 1999) Kawasaki Igakkaishi 25(4) : 287-295, 1999
