Hematoporphyrin Derivative Photochemotherapy of Experimental Bladder Tumors

Abstract

Recent studies have shown that disruption of tumor blood flow is a major consequence of hematoporphyrin derivative [HpD] photochemotherapy. A series of experiments was undertaken on the transplantable N-(4-(5-nitro-2-furyl)-2-thiazolyl)-formamide induced urothelial tumor in Fischer 344 rats to determine a dose response for both HpD and light. Tumor blood flow was used as the biologic criteria of response. HpD doses of 10 .mu.g/g body wt or above were necessary to cause a significant decrease in tumor blood flow when the tumors were illuminated with 360 J/cm2 of noncoherent red light (> 590 nm). With a constant HpD dose of 20 .mu.g/g body wt, significantly lower tumor blood flows were observed with 240 J/cm2 and above. To correlate dose response to tumor regression, experiments were done in which tumor dry wt were determined 3 wk after completion of photochemotherapy (360 J/cm2). HpD doses of 10 .mu.g/g body wt or above were necessary to induce tumor regression. These studies support the hypothesis that disruption of tumor blood flow is a tumoricidal mechanism of HpD photochemotherapy.