Increased survival of CD1 mice bearing dimethylhydrazine induced primary colon and anal cancers by difluoromethylornithine with concomitant increase in angiosarcoma incidence.

Sixty CDl mice received dimethylhydrazine 20 mg/kg s.c. once weekly for 26 weeks to induce colorectal cancer. At this time the animals harbored frank colorectal cancer and early epidermoid cancer. The animals were divided into six groups that were subjected to the following treatments: none, MTP immunotherapy (MTP) alone, radiotherapy (R) alone, difluoromethylornithine (DFMO) chemotherapy alone and combinations of R+DFMO and R+DFMO+MTP. Criteria of evaluation of treatment efficacy were: number of colorectal tumor lesion and their staging at death, the incidence and size of anal cancer at death and survival time. Radiotherapy alone was marginally effective and MTP treatment was moderately effective in preventing anal cancer and reducing the number of colorectal tumors as well as their size. DFMO was exceptional in preventing anal cancer in a majority of animals and increasing animal survival; the latter effect was due to its preventive action against pyelonephritis, the major cause for animal death. However, in DFMO treated animals, the incidence of angiosarcoma increased from 10-16% (in the absence of DFMO) to 35-50% (in the presence of DFMO). The most effective treatment of the colorectal tumor was the triple combination of R + DFMO + MTP.