Hematoporphyrin derivative photochemotherapy of experimental bladder tumors

Recent studies have shown that disruption of tumor blood flow is a major consequence of hematoporphyrin derivative 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 hematoporphyrin derivative and light. Tumor blood flow was used as the biologic criteria of response. Hematoporphyrin derivative doses of 10 micrograms./gm. body weight or above were necessary to cause a significant decrease in tumor blood flow when the tumors were illuminated with 360 joules/cm.2 of noncoherent red light (greater than 590 nm.). With a constant hematoporphyrin derivative dose of 20 micrograms./gm. body weight, significantly lower tumor blood flows were observed with fluences of 240 joules/cm.2 and above. In order to correlate dose response to tumor regression, experiments were done in which tumor dry weights were determined 3 weeks after completion of photochemotherapy (360 joules/cm.2). Hematoporphyrin derivative doses of 10 micrograms./gm. body weight or above were necessary to induce tumor regression. These studies support the hypothesis that disruption of tumor blood flow is a tumoricidal mechanism of hematoporphyrin derivative photochemotherapy.