Sequence and Time Interval in Combination of Irradiation and Cis-Diamminedichloroplatinum in C3H Mouse Fibrosarcoma

Ha, Sung When; Choi, Eun Kyung; Park, Charn Il

Abstract

Experiments have been carried out with C3H mouse fibrosarcoma (FSa II) to determine the effect of different sequence and time intervals between irradiation and administration of cis-diamminedichloroplatinum(cia-DDP) with gross tumors (6 mm in diameter), microscopic tumors (3 days after transplantation of 103 cells) and cells in culture. The drug was administered either 24, 12, 8, 4, 2, 1, 0.5 hour before irradiation, immediately before irradiation, or 0.5, 1, 2, 4, 8, 12, 24 hours after irradiation. In case of in vivo studies, tumor growth delay was used as an end point. Clonogenic cell surviving fraction was used for in vivo studies. Tumor growth delay for gross tumor after 10 Gy radiation plus 10 mg/kg cis-DDP ranged from 0.3 to 10.66 days and the enhancement ratio ranged from 1.37 to 2.23. The most effective combination was whets cis-DDP was given 4 hours before irradiation. Tumor growth delay for microscopic tumor after 5 Gy of radiation and 5 mg/kg of cia-DDP ranged from 3.55 to 11.98 days with enhancement ratio from 2.05 to 6.92. Microscopic tumors showed response significantly greater than additive in every time interval and the most effective treatments were when cis-DDP was given 2 and 1 hour before irradiation. In in vitro experiment, the surviving fraction after 6 Gy of radiation and 1 hour exposure to 4 mu cia-DDP fluctuated as a function of time between treatments, but the difference between maximum and minimum surviving fractions was very small. According to the above results the sequence and time interval between irradiation and chemotherapy is very critical especially for the management of microscopic tumors as in the case of postoperative adiuvant treatment.