Photofrin Uptake in the Tumor and Normal Tissues of Patients Receiving Intraperitoneal Photodynamic Therapy

Abstract

Purpose: A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. Experimental Design: Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. Results: Photofrin concentration was measured in 301samples collected from 58 of100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P < 0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P = 0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (V2.31). Conclusions: Some selectivity is found in Photofrin uptake between tumor and normal tissues of the peritoneal cavity, but absolute differences in drug uptake relative to toxicity-limiting normal tissues (intestine) are small. This narrow differential in drug selectivity likely contributes to a narrow window in therapeutic application, which has been previously reported.

Pilot Study on Light Dosimetry Variables for Photodynamic Therapy of Barrett's Esophagus with High-Grade Dysplasia

“…The present study, which used an extraction method to quantify the porfimer sodium in mucosal biopsy samples, reports a 10-fold variability in esophageal uptake of porfimer sodium. A similar wide variability among patients in porfimer sodium concentration has been reported in previous studies of other tissues (17,21). Perhaps related to the limited number of patients in this study, this variation in the porfimer sodium tissue content in itself was not shown to be predictive of treatment outcome.…”

“…Holmer et al (15) measured the optical properties of normal, Barrett's, and cancer tissue for modeling of light flux and absorption throughout the esophagus during PDT. Improved tissue characterization and more accurate determination of optical properties are critically important for mathematical modeling and Monte Carlo simulations of optimal PDT dosimetry for PDT light dosimetry planning (16,17).…”

Photodynamic Therapy: A Light in the Darkness?

“…Technical issues and normal tissue toxicities currently preclude the broader applicability of PDT for the treatment of invasive malignancies (4,11,12). The use of PDT in these settings has been associated with a narrow therapeutic index and recurrent disease is common.…”

Effects of photodynamic therapy for superficial esophageal squamous cell carcinoma in vivo and in vitro

“…It involves administration of a photosensitizing drug followed by the application of a specific wavelength of light, leading to intracellular photoexcitation and injury (11). Theoretically, PDT can cure gastrointestinal neoplasms contained within the submucosal layer (10,12,13). It is a highly effective, painless, and usually well-tolerated procedure that is simple to perform (10,13).…”