Marked survival prolongation of mice bearing a transplantable colon adenocarcinoma by treatment with radioactive platinum-[125I]histamine complex. Preliminary report.

BACKGROUND Recently, a new PtCl2-histamine complex, and its radioactive analogues labelled with I-131 and I-125 have been synthesised and investigated both in vitro and in vivo. In this preliminary report the survival rate of radioactive platinum-[125I] histamine therapy in tumour-bearing mice is demonstrated. MATERIAL AND METHODS A murine model of transplantable colon adenocarcinoma (C38) in C57BL/6 mice (15 days postimplantation) was used for the experiment. Three groups of animals were treated every 2-3 days with five intraperitoneal injections of the following preparations: PtCl2Hist (total dose of Pt--125 micromol/kg), PtCl2[125I]Hist (total dose of I-125--4.2 MBq; Pt--13 micromol/kg), and "Active/Cold"--PtCl2[125I]Hist/PtCl2Hist (I-125--4.2 MBq; Pt--125 micromol/kg). A solution of 15% dimethylformamide in saline was applied to the control group. A survival analysis with the Kaplan-Meier estimation of survival curves and a statistical comparison by a log-rank test was applied to evaluate the anticancer activity of the tested preparations. RESULTS Treatment of the animals with platinum-histamine preparations resulted in a significant prolongation of survivals, especially if the radioactive complex with carrier-added PtCl2Hist (p < 0.005) was applied. The highest, almost a 60% prolongation of survival was observed in the Active/Cold group (MStr/MScon ratio = 1.58, 95% CI 1.22-1.93). For this group there was the lowest risk of death (hazard ratio HR = 0.29), whereas HR = 0.45 and 0.47 were found in the animals treated with unattended PtCl2Hist and 125I-labelled complex, respectively. CONCLUSION The significant enhancement of in vivo anti-cancer activity by a concomitant combination of the therapeutic factors, i.e. cytotoxic/cytostatic activity of the platinum(II)-histamine and the Auger electrons effects generated by the attached I-125 radionuclide, was found on the murine model of transplantable colon adenocarcinoma.