Porfimer Sodium

Safety and long term efficacy of porfimer sodium photodynamic therapy in locally advanced biliary tract carcinoma.[Pubmed:23200007]

Photodiagnosis Photodyn Ther. 2012 Dec;9(4):287-92.

BACKGROUND: In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with Porfimer Sodium promotes biliary drainage and may improve survival and quality of life. AIM: To prospectively evaluate the safety and efficacy of PDT in patients with locally advanced biliary tract carcinoma. METHODS: Eligible patients had unresectable, histologically confirmed disease, a Karnofsky performance status of >/=30% and life expectancy >12 weeks. Patients received 2mg/kg i.v. of Porfimer Sodium, followed by endobiliary laser activation and stent replacement 48 h later. Patients were assessed clinically and radiologically before treatment and on day 28, and followed up thereafter at three-monthly intervals until death. RESULTS: 36 patients were entered over an 18 months period: 14 males, 22 females, with a median age of 65 (30-79)yr and performance status of 80 (50-100). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. The median survival was 12 (1-84) months. CONCLUSIONS: Porfimer Sodium PDT can be delivered safely to patients with biliary tract cancer and is suitable for testing in phase III studies (UKCRN ID 1218).

Porfimer sodium photodynamic therapy in the treatment of early oesophageal carcinoma.[Pubmed:25047560]

Photodiagnosis Photodyn Ther. 2007 Dec;4(4):244-8.

BACKGROUND: The gold standard treatment of early oesophageal carcinoma is oesophagectomy but the elderly population affected are often medically unfit for this radical intervention and less invasive curative options are required. We describe our experience of Porfimer Sodium photodynamic therapy (PDT) as an alternative to surgery in such a patient group. METHODS: From 1999 to 2005 28 oesophageal cancer patients were found to have early stage disease based initially on endoscopy/CT and latterly on CT/endoscopic ultrasound (EUS) criteria. Although potentially suitable for major surgical resection these patients were judged to be medically unfit and were selected to have PDT. Patients were followed up endoscopically at 6-12-week intervals indefinitely with biopsy of the treated area. RESULTS: 18/28 patients had an initial complete response 8 weeks post procedure. One patient died before reassessment of unrelated disease. Nine patients were non-responders. 7/18 complete responders remained disease free for a mean follow up period of 1166 days (249-2019). 11/18 developed recurrent local disease treated with further PDT with a median survival of 770 days (254-2049). Fourteen patients had EUS staging which accurately predicted response: all T1N0 patients (9/14) had initial complete response to treatment although 5/9 have required further PDT. All remain disease free at a follow up of 1103 days (249-2019). No patients with T2/3N0 disease had complete response to treatment. The major complication of PDT encountered was stricture formation which occurred in 50% of cases and required a median of five dilations (range 1-31). CONCLUSIONS: Porfimer Sodium PDT is a potentially curative treatment in patients with early oesophageal carcinoma who may be unfit or unwilling to undergo major surgery.

Photosensitization reaction-induced acute electrophysiological cell response of rat myocardial cells in short loading periods of talaporfin sodium or porfimer sodium.[Pubmed:21114668]

Photochem Photobiol. 2011 Jan-Feb;87(1):199-207.

Electrophysiological responses of rat myocardial cells to exogenous photosensitization reactions for a short period of incubation with two photosensitizers, talaporfin sodium or Porfimer Sodium, were measured in a subsecond time scale. The loading period of the photosensitizer when the photosensitizer might not be taken up by the cells was selected as 15min, which was determined by the fluorescence microscopic observation. We measured the intracellular Ca(2+) concentration ([Ca(2+) ](in) ) by using a fluorescent Ca(2+) indicator, Fluo-4 AM, under a high-speed confocal laser microscope to evaluate the acute electrophysiological cell response to the photosensitization reaction. The measured temporal change in Fluo-4 fluorescence intensity indicated that the response to the photosensitization reaction might be divided into two phases in both photosensitizers. The first phase is acute response: disappearance of Ca(2+) oscillation when irradiation starts, which might be caused by ion channel dysfunction. The second phase is slow response: [Ca(2+) ](in) elevation indicating influx of Ca(2+) due to the concentration gradient. The continuous Ca(2+) influx followed by changes in cell morphology suggested micropore formation on the surface of the cell membrane, resulting in necrotic cell death.

Porfimer-sodium (Photofrin-II) in combination with ionizing radiation inhibits tumor-initiating cell proliferation and improves glioblastoma treatment efficacy.[Pubmed:23114641]

Cancer Biol Ther. 2013 Jan;14(1):64-74.

Tumor relapse and tumor cell repopulation has been explained partially by the drug-free break period between successive conventional treatments. Strategies to overcome tumor relapse have been proposed, such as the use of chemotherapeutic drugs or radiation in small, frequent fractionated doses without an extended break period between treatment intervals. Yet, tumors usually acquire resistance and eventually escape the therapy. Several mechanisms have been proposed to explain the resistance of tumors to therapy, one of which involves the cancer stem cell or tumor-initiating cell (TIC) concept. TICs are believed to resist many conventional therapies, in part due to their slow proliferation and self-renewal capacities. Therefore, emerging efforts to eradicate TICs are being undertaken. Here we show that treatment with Photofrin II, among the most frequently used photosensitizers, sensitized a TIC-enriched U-87MG human glioblastoma cell to radiation, and improve treatment outcome when used in combination with radiotherapy. A U-87MG tumor cell population enriched with radiation-resistant TICs becomes radio-sensitive, and an inhibition of cell proliferation and an increase in apoptosis are found in the presence of Photofrin II. Furthermore, U-87MG tumors implanted in mice treated with Photofrin II and radiation exhibit a significant reduction in angiogenesis and vasculogenesis, and an increased percentage of apoptotic TICs when compared with tumors grown in mice treated with radiation alone. Collectively, our results offer a new possible explanation for the therapeutic effects of radiosensitizing agents, and suggest that combinatorial treatment modalities can effectively prolong treatment outcome of glioblastoma tumors by inhibiting tumor growth mediated by TICs.