Effect of dihydroxyanthraquinone on the response of a rat solid tumor to radiation therapy

Dihydroxyanthraquinone (DHAQ, NSC 279836, a new cancer chemotherapeutic agent presently in clinical trials) was tested, alone and in combination with radiation, for therapeutic effectiveness in a rat solid tumor model. The Walker 256 fibrosarcoma was implanted subcutaneously in the leg via trochar so as to yield palpable tumors within 7-11 days. When tumor diameters reached 1 cm, the animals were treated as follows: as controls; with DHAQ (3.0 mg/kg, i.p.); with 300 KVP x-rays (15 Gy to the tumor-burdened leg); or with a combination of DHAQ and radiation. Tumor diameters were measured three times a week to monitor the response to therapy. DHAQ alone had no effect on tumor growth rate. Radiation alone produced a delay in tumor growth. The combination of DHAQ and radiation resulted in a consistently better therapeutic response than did radiation only, but at only a marginal level of statistical significance (0.05 less than p less than 0.10). However, there were 3/10 long-term survivors (greater than 80 days post treatment) without evidence of tumor in the combination therapy group; whereas all animals in the radiation group died or were sacrificed because of progressive tumor growth by day 71. These results suggest that even though DHAQ is only minimally effective against this rat solid tumor when used alone, there may still be some added therapeutic benefit derived from a combination of DHAQ and radiation therapy.