ANTITUMOR EFFECTIVENESS OF ELECTROCHEMOTHERAPY WITH CIS-DIAMMINEDICHLOROPLATINUM(II) IN MICE

One of the ways to increase drug delivery into cells and tissues is by a local application of short, intense electric pulses, Le., electrope rmeabilization. This approach is used in electrochemotherapy to potent iate antitumor effectiveness of chemotherapeutic drugs. To determine w hether electropermeabilization can potentiate antitumor effectiveness of cis-diamminedichloroplatinum(II) (CDDP), electrochemotherapy with C DDP was tested in vitro and in vivo on s.c. SA-I, EAT, and melanoma B1 6 tumors in mice. Electric pubes were applied to the tumors by percuta neously placed electrodes after i.v. injection of CDDP. Severalfold po tentiation of CDDP antitumor effectiveness with electric pulses was ob tained, inducing partial or complete responses in tumor growth. Electr ochemotherapy was CDDP dose dependent, as wed as dependent upon the am plitude of electric pulses. Also important was the sequencing and the interval of CDDP administration, relative to application of electric p ulses. Specifically, a good antitumor effect without side effects was obtained with eight electric pulses (electric pulse amplitude, 1040 V; repetition frequency, 1 Hz; pulse width, 100 mu s; electrode distance , 8 mm; 1300 V/cm) applied 3 min after i.v. injection of 4 mg/kg CDDP. With a higher CDDP dose (8 mg/kg), some long-term complete responses were obtained (14%) on melanoma B16 tumors. Thus, electrochemotherapy with CDDP offers an approach to making chemotherapy with CDDP more eff ective.