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

Abstract

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, 2.1and 20.1months; gastrointestinal cancers,1.8 and11.1months; 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 photosensitizeruptake, and the heterogeneity in tissue optical properties may account for the lack of efficacy observed.

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates

“…Therefore, in the clinic, these agents are photoactivated intraoperatively or endoscopically. Early clinical trials demonstrated feasibility and efficacy for photodynamic therapy of peritoneal metastases (27) with the major challenge being bowel perforations resulting from a lack of tumor selectivity (38). taPIT overcomes this poor tumor selectivity and bowel toxicity.…”

“…Because photodynamic agents are mechanistically distinct from traditional treatment modalities (13,14), are effective against radioresistant and chemoresistant cells (19,20,26), and can also resensitize resistant cells to chemotherapy (20,23), the development of PIT is of importance for overcoming drug resistance. In fact, photodynamic therapy has been used in the treatment of disseminated peritoneal disease with some success intraoperatively (27) and endoscopically in the lung, bladder, and esophagus (SI Text, Note S1).…”

In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring

“…This inherent capability to integrate imaging and PDT treatment, which makes PS imaging particularly conducive to online monitoring of therapy response, was not used in the studies referenced above. It is also worth noting that the application of PDT to the treatment of OvCa has shown promise in clinical trials (Sindelar et al, 1991;Hendren et al, 2001;Hahn et al, 2006), although further studies are warranted to establish optimal conditions for light and PS delivery in the clinic.…”

Robotic applications in abdominal surgery: their limitations and future developments

“…There is early evidence that photosensitizing agents are taken up by peritoneal metastatic nodules, implying that PDT here is feasible, although a clinical benefit has not yet been shown (28). It is suggested that a more selective photosensitizing agent is required to improve the results, but also a better light delivery mechanism.…”