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Intraperitoneal Photodynamic Therapy of Human Epithelial Ovarian Carcinomatosis in a Xenograft Murine Model¹

Wellman Laboratories of Photomedicine [K. L. M., D. K., M. R. H., M. B., T. H.], WLM 222B and Vincent Gynecologic Oncology Service [K. L. M., D. K.], VBK-1, Massachusetts General Hospital, Boston, Massachusetts 02114, and Ontario Cancer Institute/Princess Margaret Hospital, Department of Clinical Physics, 610 University Ave., Toronto, Ontario, M5G 2M6, Canada [L. L.]

The objective of this investigation was to determine the efficacy of i.p. photodynamic therapy (PDT) against solid, multifocal ovarian carcinoma using a newly described NIH:OVCAR-5 induced murine model. PDT was initiated when diffuse microscopic disease and small multifocal tumor nodules were present, similar to the extent of residual carcinoma that may persist clinically after laparotomy and tumor debulking. The photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), was administered in a dose of 0.25 mg/kg body weight i.p. 90 min prior to light exposure. An argon-pumped dye laser was used to deliver low intensity light (20 J) i.p. through a cylindrically diffusing fiberoptic tip. Treatment regimens consisted of a series of three to five treatments at 3-7-day intervals, with the extent of macroscopic disease or death from disease being the evaluable outcome parameters for tumoricidal and survival studies, respectively. The mean tumor burden at necropsy for treated animals was 0.034 ± 0.014 g compared to 0.379 ± 0.065 g in untreated controls (P < 0.001). Survival studies were initiated in two groups at day 7 and day 14 following cell inoculation. The first group received either three or five treatments at 5-day intervals, and both had a significant increase in median survival compared to untreated controls (57 and 53 days, respectively, compared to 43 days, P < 0.05). The second group was treated every 7 days until death and also had a significant survival advantage over controls (57 days compared to 47 days, P < 0.05). These studies suggest that benzoporphyrin derivative mono acid ring A-mediated PDT is a feasible, well-tolerated, experimental treatment approach that elicits a tumoricidal response against diffuse, solid i.p. disease in tumor-bearing mice, with concomitant prolongation of survival and needs careful optimization.

¹ This work was supported by NIH Grant R01 AR40352, Office of Naval Research Contract N 00014-94-1-0927, the Massachusetts General Hospital Laser Center (partial fellowship to D. K.).

² To whom requests for reprints should be addressed.

Received 9/ 8/95. Accepted 1/ 2/96.

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