CIS Platin By Continuous Infusion with Concurrent Radiation in Malignant Tumors (A Phase I-II Study)

Abstract

Cis-Diamminedichloroplatinum II (Cis-DDP or Cisplatin) the first of the group of platinum coordination complexes used effectively against some human malignancies, was found, since 1974, to potentiate irradiation effects on experimental tumors (1). Since 1977 Douple and Richmond (2–4) have concluded, based on a number of experimental studies on E coli bacterium (5), V-79 Chinese hamster cells, mouse mammary adenocarcinoma, etc. that cisplatin sensitizes hypoxic cells to radiation, increases DNA susceptability to radiation damage and at the same time inhibits the radiation induced repair of potentially lethally damaged DNA. A convincing experimental demonstration of the radiosensitizing effect of cisplatin was obtained by Kyriazis et al (6) on a human bladder carcinoma implanted in nude mice. The mice receiving both modalities of treatment had a statistical significantly longer response and survival than those receiving radiation alone. Other experimental data suggested that the Cisplatin-Radiation interaction was enhanced when radiation was administered in multiple fractions (7) and that cisplatin could be possibly more effective when administered by continuous infusion because even so it is a phase cycle nonspecific drug, DDP acts preferentially on the G₁ phase (8). On clinical grounds preliminary studies (9–11) of cisplatin-radiation combination have used only bolus i.v. administration of the drug. While indicating a favorable trend they have been inconclusive in proving its radiosensitizing effect.