A Phase II Trial of Intraperitoneal Photodynamic Therapy for Patients with Peritoneal Carcinomatosis and Sarcomatosis

Purpose: A previous phase I trial of i.p. photodynamic therapy established the maximally tolerated dose of Photofrin (Axcan Pharma, Birmingham, AL)-mediated photodynamic therapy and showed encouraging efficacy. The primary objectives of this phase II study were to determine the efficacy and toxicities of i.p. photodynamic therapy in patients with peritoneal carcinomatosis and sarcomatosis. Experimental Design: Patients received Photofrin 2.5 mg/kg i.v. 48 hours before debulking surgery. Intraoperative laser light was delivered to the peritoneal surfaces of the abdomen and pelvis. The outcomes of interest were ( a ) complete response, ( b ) failure-free survival time, and ( c ) overall survival time. Photosensitizer levels in tumor and normal tissues were measured. Results: One hundred patients were enrolled into one of three strata (33 ovarian, 37 gastrointestinal, and 30 sarcoma). Twenty-nine patients did not receive light treatment. All 100 patients had progressed by the time of statistical analysis. The median failure-free survival and overall survival by strata were ovarian, 2.1 and 20.1 months; gastrointestinal cancers, 1.8 and 11.1 months; sarcoma, 3.7 and 21.9 months. Substantial fluid shifts were observed postoperatively, and the major toxicities were related to volume overload. Two patients died in the immediate postoperative period from bleeding, sepsis, adult respiratory distress syndrome, and cardiac ischemia. Conclusions: Intraperitoneal Photofrin-mediated photodynamic therapy is feasible but does not lead to significant objective complete responses or long-term tumor control. Heterogeneity in photosensitizer uptake and tumor oxygenation, lack of tumor specificity for photosensitizer uptake, and the heterogeneity in tissue optical properties may account for the lack of efficacy observed.