Photofrin Research Articles

Treatment for Barrett's oesophagus.

Treatments for Barrett's oesophagus, the precursor lesion of adenocarcinoma, are available but whether these therapies effectively prevent the development of adenocarcinoma, and in some cases eradicate the Barrett's oesophagus segment, remains unclear. To summarise, quantify and compare the efficacy of pharmacological, surgical and endoscopic treatments for the eradication of dysplastic and non-dysplastic Barrett's oesophagus and prevention of these states from progression to adenocarcinoma. We searched CENTRAL (The Cochrane Library 2004, issue 4), MEDLINE (1966 to June 2008) and EMBASE (1980 to June 2008). Randomised controlled trials (RCTs) comparing medical, endoscopic or non-resectional surgical treatments for Barrett's oesophagus. The primary outcome measures were complete eradication of Barrett's and dysplasia at 12 months, and reduction in the number of patients progressing to cancer at five years or latest time point. Three authors independently extracted data and assessed the quality of the trials included in the analysis. Sixteen studies, including 1074 patients, were included. The mean number of participants in the studies was small (n = 49; range 8 to 208). Most studies did not report on the primary outcomes. Medical and surgical interventions to reduce symptoms and sequelae of gastro-oesophageal reflux disease (GORD) did not induce significant eradication of Barrett's oesophagus or dysplasia. Endoscopic therapies (photodynamic therapy (PDT with aminolevulinic acid or porfimer sodium), argon plasma coagulation (APC) and radiofrequency ablation (RFA)) all induced regression of Barrett's oesophagus and dysplasia. The data for photodynamic therapy were heterogeneous with a mean eradication rate of 51% for Barrett's oesophagus and between 56% and 100% for dysplasia, depending on the treatment regimens. The variation in photodynamic therapy eradication rates for dysplasia was dependent on the drug, source and dose of light. Radiofrequency ablation resulted in eradication rates of 82% and 94% for Barrett's oesophagus and dysplasia respectively, compared to a sham treatment. Endoscopic treatments were generally well tolerated, however all were associated with some buried glands, particularly following argon plasma coagulation and photodynamic therapy, as well as photosensitivity and strictures induced by porfimer sodium based photodynamic therapy in particular. Despite their failure to eradicate Barrett's oesophagus, the role of medical and surgical interventions to reduce the troubling symptoms and sequelae of GORD is not questioned. Whether therapies for GORD reduce the cancer risk is not yet known. Ablative therapies have an increasing role in the management of dysplasia within Barrett's and current data would favour the use of radiofrequency ablation compared with photodynamic therapy. Radiofrequency ablation has been shown to yield significantly fewer complications than photodynamic therapy and is very efficacious at eradicating both dysplasia and Barrett's itself. However, long-term follow-up data are still needed before radiofrequency ablation can be used in routine clinical care without the need for very careful post-treatment surveillance. More clinical trial data and in particular randomised controlled trials are required to assess whether or not the cancer risk is reduced in routine clinical practice.

PHOTOFRIN‐mediated photodynamic therapy for treatment of early stage (Tis‐T2N0M0) SqCCa of oral cavity and oropharynx

To evaluate the efficacy of dihematoporphyrin ether (PHOTOFRIN)-mediated photodynamic therapy (PDT) for the treatment of diffuse field cancerization and Tis-T2N0M0 squamous cell carcinoma (SqCCA) of the oral cavity and oropharynx in patients not amenable to or that have failed conventional head and neck cancer treatment. This is a retrospective study of 30 patients with Tis-T2N0M0 SqCCA of the oral cavity/oropharynx treated with PDT. Intravenous PHOTOFRIN (porfimer sodium) (dose 2.0 mg/kg) was administered outpatient, followed 48-60 hours later by intraoperative photoactivation at 630 nm via fiberoptic microlens surface delivery (light dose 50-100 J/cm(2)) or interstitial implantation via cylindrical diffuser fiberoptic delivery (light dose 50-100 J/cm). Twenty-four of 30 patients (80%) have demonstrated complete remission (follow-up 3-144 months). There were six patients who had partial remission with recurrence observed at 3, 3, 5, 9, 23, and 26 months subsequently retreated with conventional therapy. Eleven of 24 patients were cancer disease free at 2 years following PDT. PDT provides a surgical oncologic modality for potentially curative treatment of early stage oral cavity and oropharyngeal malignancies either as a primary modality or for treatment in patients that have previously failed surgery and/or radiation therapy.

The Role of Photodynamic Therapy in the Esophagus

Photodynamic therapy (PDT) is a drug and device therapy using photosensitizer drugs activated by laser light for mucosal ablation. Porfimer sodium PDT has been used extensively with proven long-term efficacy and durability for the ablation of Barrett esophagus and high-grade dysplasia. and early esophageal adenocarcinoma. However, continued use is hampered by an associated stricture risk and prolonged photosensitivity (4-6 weeks). Promising single-center European studies using other forms of PDT, such as aminolevulinic acid PDT, have not been replicated elsewhere, limiting the widespread use of other forms of PDT. Future use of PDT in esophageal disease depends on the development of improved dosimetry and patient selection to optimize treatment outcomes, while minimizing adverse events and complications.

Potentiating Effect of .BETA.-Glucans on Photodynamic Therapy of Implanted Cancer Cells in Mice

Photodynamic therapy (PDT) combines a drug or photosensitizer with a specific type of light to kill cancer cells. The cellular damage induced by PDT leads to activation of the DNA damage repair, which is an important factor for modulating tumor sensitivity to this treatment. beta-Glucans are natural polysaccharides that bind complement receptor 3 on the effector cells, thereby activating them to kill tumor cells during PDT. The hypothesis of the present study was that adjuvant therapy with beta-glucans would increase the efficacy of PDT. C57BL/6 female mice were subcutaneously implanted with Lewis lung carcinoma cells. Ten days after implantation, the mice were administered intravenously sodium porfimer (10 mg/kg) 24 h prior to laser irradiation, with or without oral administration of beta-glucan (400 microg/d/mouse, 5 days) from either barley, baker's yeast, or marine brown algae that contains the storage glucan, laminarin. Tumor volume and necrotic area in excised tumors were measured. The expression of proliferating cell nuclear antigen (PCNA) was determined as an indicator of the activity of the DNA damage repair system. PDT in combination with each beta-glucan significantly reduced tumor growth (P < 0.05, n = 10) and expression of PCNA (P < 0.001, n = 9), and increased necrosis in tumor tissues (P < 0.001, n = 9). Furthermore, each structurally different <beta-glucan exerted similar potentiating effects on PDT. The present findings show that beta-glucans enhance the tumor response to PDT, resulting in pronounced necrosis of PDT-treated tumors and suppression of the DNA damage repair system.

Theoretical study of the linear and nonlinear optical properties of the Photosensibilizer molecules: Photofrin and foscan in gas phase

A theoretical study on the static linear () and nonlinear ( and ) optical properties in gas phase of Photofrin and Foscan molecules is reported. These compounds are known as porphyrin derivatives w...

Photodynamic Therapy for Head and Neck Dysplasia and Cancer

To determine the response of dysplasia, carcinoma in situ (CIS), and T1 carcinoma of the oral cavity and larynx to photodynamic therapy with porfimer sodium. Prospective trial. A National Cancer Institute-designated cancer institute. Patients with primary or recurrent moderate to severe oral or laryngeal dysplasia, CIS, or T1N0 carcinoma. Porfimer sodium, 2 mg/kg of body weight, was injected intravenously 48 hours before treatment. Light at 630 nm for photosensitizer activation was delivered from an argon laser or diode laser using lens or cylindrical diffuser fibers. The light dose was 50 J/cm(2) for dysplasia and CIS and 75 J/cm(2) for carcinoma. Response was evaluated at 1 week and at 1 month and then at 3-month intervals thereafter. Response options were complete (CR), partial (PR), and no (NR) response. Posttreatment biopsies were performed in all patients with persistent and recurrent visible lesions. Thirty patients were enrolled, and 26 were evaluable. Mean follow-up was 15 months (range, 7-52 months). Twenty-four patients had a CR, 1 had a PR, and 1 had NR. Three patients with oral dysplasia with an initial CR experienced recurrence in the treatment field. All the patients with NR, a PR, or recurrence after an initial CR underwent salvage treatment. Temporary morbidities included edema, pain, hoarseness, and skin phototoxicity. Photodynamic therapy with porfimer sodium is an effective treatment alternative, with no permanent sequelae, for oral and laryngeal dysplasia and early carcinoma. clinicaltrials.gov Identifier: NCT00530088.

Photodynamic Therapy (PDT) for Barrett's Esophagus with Dysplasia: Long-Term Follow-Up of Gastroesophageal Junction Area Is Recommended

Introduction: PDT is an effective endoscopic treatment for eliminating high grade dysplasia (HGD) in Barrett's esophagus (BE). However after clearance of Barrett's esophagus and dysplasia, HGD and cancer have been reported within the 2 cm area proximal to the gastroesophageal junction on long term follow-up. This study reviews long term histologic outcomes following PDT elimination of BE and dysplasia within the distal 2 cm of the esophagus, arbitrarily labeled the “hot zone”. Methods: Charts of 365 consecutive porfimer sodium PDT patients treated between December 1993 and September 2002 were reviewed. 135 patients were followed for a minimum of 4 years (maximum of 12 years, mean 6.8 years). 65 patients remained clear of their Barrett's esophagus for the first four years after PDT. The histologic findings in the “hot zone” in those 65 patients were analyzed for 4-12 years after PDT. Pre-PDT histology consisted of HGD in 44 cases, 6 early cancers (CA), 14 low grade dysplasias (LGD) and 1 intestinal metaplasia (IM). Four quadrant large particle biopsies at 2 levels over the distal 2 cm of the initial BE length performed during each follow-up were reviewed. Results: Analyzing the worst-case histology during the 4-12 years follow-up, cancer occurred in the distal 2 cm of the esophagus in 4 patients (6.1%), HGD in 1 (1.5%), LGD in 3 (4.6%), indefinite for dysplasia in 1 (1.5%), and intestinal metaplasia in 23 patients (35.3%). 33 patients (50.8%) were completely clear of their Barrett's mucosa during the follow-up period. All patients continued to receive endoscopic ablation as needed for recurrent BE. Reviewing the last available follow-up biopsy results, 3 patients (4.6%) had cancer, 1 patient (1.5%) had LGD, 1 patient (1.5%) had indefinite for dysplasia and 12 patients (18.5%) had intestinal metaplasia. 48 patients (74%) were completely clear of BE on last follow-up visit. Conclusion: Long term endoscopic biopsy follow-up after PDT ablation and clearing of dysplasia in BE is recommended to detect recurrent BE, dysplasia or cancer within the distal 2 cm (“hot zone”) of the esophagus.

Endoscopic Resection for Solitary Nodular Lesions After Ablation of Esophageal Dysplasia and Carcinoma

Purpose: Nodular lesions in Barrett's esophagus [BE] are suspicious for harboring invasive carcinoma. Endoscopic resection [ER] is of diagnostic and therapeutic importance for the removal and histologic staging of these lesions. There are few data available, however, regarding the safety and utility of ER for nodular lesions detected at surveillance endoscopy after ablation therapy. Methods: After IRB approval, patients with solitary nodular lesions detected after ablation therapy were identified. Medical records were abstracted for demographics, pre-ablation histology and endoscopic ultrasound [EUS] findings, ablation technique and ER procedure details including complications and disease recurrence. Results: Twelve patients with solitary nodular lesions were identified between 2001-08 after previous endoscopic ablation using porfimer sodium photodynamic therapy (PsPDT) or radiofrequency ablation (RFA) (10 were men; mean age 72 years [range: 43-82]). PsPDT was performed for Barrett's high grade dysplasia (7 pts); esophageal adenocarcinoma (1 pt) and squamous cell carcinoma (1 pt), both T1N0MX by EUS staging. RFA was performed for Barrett's high grade dysplasia in 3 pts. At follow up endoscopy, (median 335 days after endoscopic ablation; range: 105-1843 days) nodular mucosa suspicious for disease recurrence was detected. EUS findings were T1sm1 or less in each case and pts were referred for ER that was successful in 11/12 patients using either Wilson Cook Duette or Olympus cap technique with no complications. ER was unsuccessful in one patient (no lift sign). ER specimen histopathology found BE-HGD (3 pts), T1m adenocarcinoma (3 pt) and benign, hypertrophic glandular mucosa (5 pts). ER findings prompted further therapy (repeat endoscopic ablation in 3 pts, esophageal resection surgery in 1 pt, and failed esophageal resection in 1 pt due to adhesions from a previous surgery). Mean follow up after successful ER and negative adenocarcinoma in need of surgical resection was 303 days (27-676 days) with no further complications or disease recurrence. The patient who had an attempted but unsuccessful EMR due to lack of lift sign was later found to have adenocarcinoma and underwent esophagectomy as repeat PsPDT followed by liquid nitrogen cryotherapy treatment was unsuccessful. Conclusion: In our series of patients with nodular lesions detected at surveillance endoscopy after endoscopic therapy for esophageal dysplasia or carcinoma, ER was safely performed in most patients (11/12) and detected dysplasia or carcinoma in 6/11 patients leading to further ablation therapy and surgery.

Endoscopic Therapy for Barrett's Esophagus

Recent retrospective cohort data and a prospective randomized sham controlled trial have clearly documented the impact of endoscopic ablation therapy on dysplasia and Barrett's esophagus (BE). The clinical indications for ablation of BE includes high-grade dysplasia and intramucosal adenocarcinoma. The techniques of resection of mucosal irregularities and of ablation are reviewed, primarily thermal and photodynamic ablation. Ablation of BE with neoplasia has appropriately entered the clinical arena.

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

Photodynamic therapy (PDT) is used to treat Barrett's esophagus with high-grade dysplasia and mucosal carcinoma. Outcomes are variable with some patients having persistent disease, whereas others develop strictures. The aims of this study were (a) to compare porfimer sodium tissue uptake, light dose, and esophageal thickness with clinical outcomes and (b) to determine the selectivity of porfimer sodium uptake in diseased and normal epithelium. Forty-eight hours after porfimer sodium infusion, patients underwent mucosal biopsy for quantification of the porfimer sodium. Laser light was delivered at 48 hours and again 24 or 48 hours later. Porfimer sodium was extracted from the biopsy samples and quantified using fluorescence spectroscopy. The enhanced photodynamic dose was determined as [porfimer sodium content * light dose/esophageal thickness]. PDT efficacy was determined 6 to 8 weeks later based on persistence or complete ablation of dysplasia or carcinoma. Mean porfimer sodium content of 6.2 mg/kg (range, 2.6-11.2 mg/kg) and mean total light dose of 278 J/cm (range, 225-360 J/cm) resulted in a complete treatment. Mean porfimer sodium tissue content of 3.9 mg/kg (range, 2.1-8.1 mg/kg) and mean total light dose of 268 J/cm (range, 250-350 J/cm) resulted in an incomplete treatment. The total esophageal thickness (range, 1.7-6.0 mm) and enhanced photodynamic dose were correlated with treatment outcome. Esophageal thickness is the strongest predictor of treatment outcome. The porfimer sodium content of Barrett's and normal tissue is not significantly different. "Photodynamic dose" for esophageal PDT should incorporate the esophageal thickness.

Monte Carlo Model of Stricture Formation in Photodynamic Therapy of Normal Pig Esophagus

Photodynamic therapy (PDT) is FDA-approved for use in patients with Barrett's esophagus using porfimer sodium (2 mg per kg) and a recommended light dose of 130 J cm(-1) for high grade dysplasia. Despite uniform drug and light doses, the clinical outcome of PDT is variable. A significant number of PDT cases result in esophageal strictures, a side effect related to excessive energy absorption. The purpose of this project was to model esophageal stricture formation with a Monte Carlo simulation. An original multilayer Monte Carlo computer simulation was developed for esophageal PDT. Optical absorption and scattering coefficients were derived for mucosal and muscle layers of normal porcine esophagus. Porfimer sodium was added to each layer by increasing the absorption coefficient by the appropriate amount. A threshold-absorbed light dose was assumed to be required for stricture formation and ablation. The simulation predicted irreversible damage to the mucosa with a 160 J cm(-1) light dose and damage to the muscle layer with an additional 160 J cm(-1) light dose for a tissue porfimer sodium content of 3.5 mg kg(-1). The simulation accurately modeled photodynamic stricture formation in normal pig in vivo esophageal tissue. This preliminary work suggests that the absorbed light threshold for stricture formation may be between 2 and 4 J per gram of tissue.

耳鼻咽喉科・頭頸部外科領域に対する光線力学的治療

Photodynamic therapy (PDT) is recognized as one of the treatment options for early stage cancers. This treatment is a first-line treatment for carcinoma based on a photochemical reaction in which a photosensitizer is excited by laser irradiation, causing selective death of tumor tissue. PDT greatly differs from other cancer treatments particularly because the function of organs and tissues can be preserved. We have applied the PDT using porfimer sodium activated with an excimer dye laser for head and neck cancer since 1988 and have reported the results. Since 2003, PDT using NPe6 which was synthesized from the extract from chlorophyll and activated with a diode laser, has been applied in head and neck cancer patients. Furthermore, we proved the remaining NPe6 concentration in tumor tissue was about 2 to 5 times higher than that in normal tissue in human subjects. Having already treated 100 or more cases of the head and neck cancer, we consider early stage cancer of the larynx, the tongue, mouth and oropharynx as good target indications for PDT. According to the latest treatment results of laryngeal cancer, rate of the complete remission (CR) and recurrence rates were 100% and 9.1%, respectively, and as for tongue, mouth and oropharynx cancer, the CR and recurrence rates were 100% and 8.0%, respectively, which are almost comparable with conventional treatments. No adverse experience/event was seen in terms of critical photosensitivity and blood biochemical toxicity. The pain associated with medical treatment was also slight and controllable by internal use of NSAIDs only, the healing process was also good and ingestion was possible from the first post-treatment day. PDT is a cancer treatment method which could be associated with same-day surgery, or a short-term hospital stay. Moreover, PDT has relevance for head and neck cancer patients not only as one of the treatment options for early stage cancer patients but also as a potential application to improve patients’ QOL, by decreasing the tumor size, in those patients whose tumors are inoperable, or in cases treated using combination therapy with radiation and surgery.

Photodynamic therapy for Barrett’s esophagus: does light still have a role?

Photodynamic therapy was the first treatment to have been shown to significantly decrease high-grade dysplasia and cancer in patients with Barrett's esophagus. However, its use has been limited, primarily because of the side effects, which include esophageal strictures, cutaneous photosensitivity, chest pain, and nausea and vomiting. The tolerability aspects of photodynamic therapy, as well as the dosimetry, though, can be improved with existing technologies to further develop this therapy into truly a widely applicable therapy. Studies have recently been done to help identify patients more likely to suffer stricture after photodynamic therapy. In addition there has been evidence to suggest that the efficacy of photodynamic therapy also can be limited by genetic abnormalities in the mucosa. By combining knowledge of tissue biology, optical properties of the tissue, and dosimetry issues with ablation, photodynamic therapy can still have a potentially bright future.

Optimal conditions for successful ablation of high-grade dysplasia in Barrett’s oesophagus using aminolaevulinic acid photodynamic therapy

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA-PDT) is an attractive alternative to PDT with porfimer sodium for the treatment of high-grade dysplasia (HGD) in Barrett's oesophagus (BO) because of the shorter duration of light photosensitivity and low risk of oesophageal stricture formation. Published results, however, show marked variation in its efficacy, and optimum treatment parameters have not been defined. This study investigated how the dose of ALA and the colour of the illuminating light influenced the biological effect. Twenty-seven patients were enrolled into a randomised controlled trial of red versus green (635 nm or 512 nm) laser light activation for the eradication of HGD with ALA-PDT in Barrett's oesophagus. A further 21 patients were subsequently treated with the most effective regimen. Regular endoscopic follow-up with quadrantic biopsies every 2 cm was performed. The primary outcome measure was eradication of HGD. Patient's receiving ALA at 30 mg/kg relapsed to HGD more than those receiving 60 mg/kg (P = 0.03). Additionally, for those treated with ALA 60 mg/kg, red laser light was more effective than green laser light (P = 0.008). Kaplan-Meier analysis of the 21 patients who were subsequently treated with this optimal regimen demonstrated an eradication rate of 89% for HGD and a cancer-free proportion of 96% at 36 months' follow-up. Using an ALA dose of 60 mg/kg activated by 1,000 J/cm red laser light, we found that ALA-PDT was a highly effective treatment for high-grade dysplasia in Barrett's oesophagus.

Patient predictors of histopathologic response after photodynamic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma

Photodynamic therapy (PDT) has been used extensively for endoscopic ablation of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal carcinoma. To identify patient variables that influence the likelihood of response to PDT. A retrospective cohort study. Tertiary-referral center. A total of 116 patients with Barrett's esophagus and with HGD, intramucosal carcinoma, or T1 cancer. PDT with porfimer sodium. (1) Ablation of HGD and/or intramucosal carcinoma and (2) eradication of all Barrett's epithelium. Of the patients, 51% underwent treatment for HGD and 49% of patients had intramucosal carcinoma or T1 cancer. At 12-month follow-up, ablation of HGD and/or cancer was observed in 70% of patients, and ablation of all Barrett's epithelium was observed in 39%. In multivariate analysis, the pretreatment length of Barrett's esophagus was inversely correlated with successful ablation of all Barrett's epithelium. Patients with Barrett's esophagus length more than 3 cm were less likely to experience complete ablation compared with patients with Barrett's esophagus length 3 cm or less (odds ratio [OR] 0.15 [95% CI, 0.04-0.50]). Patients with intramucosal carcinoma were not significantly less likely to experience elimination of HGD and/or cancer (OR 0.77 [95% CI, 0.30-2.00]) or ablation of all Barrett's epithelium (OR 0.82 [95% CI, 0.32-2.07]) compared with patients with HGD alone. Retrospective study, limited sample size without a control group for comparison. PDT of Barrett's esophagus with HGD, intramucosal carcinoma, or T1 cancer can result in ablation of dysplasia and/or eradication of all Barrett's epithelium. Factors associated with the likelihood of response include length of Barrett's esophagus. The presence of intramucosal carcinoma or T1 cancer was not associated with higher likelihood of treatment failure.

Squamous Overgrowth Is Not a Safety Concern for Photodynamic Therapy for Barrett's Esophagus With High-Grade Dysplasia

Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.

Photoinduced Cytotoxicity and Biodistribution of Prostate Cancer Cell-Targeted Porphyrins

A series of five porphyrin-peptide conjugates bearing one or two sequences containing a cell penetrating peptide (CPP), a nuclear localization signal (NLS), or a bifunctional CPP-NLS or NLS-CPP sequences were synthesized and investigated in vitro using PC-3M human prostate cancer cells, in comparison with FDA-approved purified hematoporphyrin derivative (Porfimer Sodium) and mTHPC. The most promising porphyrin-HIV-1 Tat (48-60) conjugate 2 [lowest dark cytotoxicity (IC50 = 38.0 microM), highest phototoxicity (IC50 = 0.40 microM at 1 J/cm2)] was further evaluated in an in vivo biodistribution study using SCID mice bearing PC-3M tumors, in comparison with purified hematoporphyrin derivative. Porphyrin conjugate 2 was more tumor selective than the hematoporphyrin derivative and accumulated to a significantly greater extent in tumors. Our results show that effective photodynamic cytotoxicity can be induced in human prostate cancer cells with minimal dark toxicity and that selective accumulation in prostate tumors can be achieved in vivo with porphyrin-targeted photosensitizers.

Dosimetric concepts for PDT

Photodynamic therapy (PDT) is a well-known treatment regimen that involves the interaction of light with a photosensitizing agent and oxygen. The treatment proceeds through the light activation of a tissue localized photosensitizer achieving an excited state. The activated photosensitizer can then react with molecular oxygen in the cell to create the putative agent, singlet oxygen. It is presumed that the liberation of this moiety is the initial photochemical event that leads to tumor destruction [1]. Relatively selective retention of the drug by hyperproliferative tissue as well as, tumors and transforming tissues compared to normal tissue, and favorable photobleaching kinetics of the drug in normal tissues, can lead to an optimal therapeutic ratio and clinical outcome in most patients. This differential therapeutic effect depends on allowing time for the injected photosensitizer to clear form the normal tissues and the circulation. PDT has often been referred to as a form of photochemotherapy or light-activated chemotherapy. However PDT achieves a localized cytotoxicity and can be compared more to radiation therapy, in particular brachytherapy, and more to a surgical approach than chemotherapy and lacks any systemic toxicity. Further unlike particularly radiation therapy, repeated applications of the photosensitizers currently used in patients, with the respective light treatments for activation, can be performed perpetually. Photodynamic therapy using porfimer sodium (Photofrin®, Axcan Pharma Inc., Canada) has been applied to the treatment of tumors in the esophagus, bronchus, bladder and skin as well as other sites. These studies have demonstrated safety and efficacy in the eradication of high-

92 TREATMENT OF 216 PORT WINE STAINS WITH PULSED DYE LASER IN ALGERIA

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.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.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).Porfimer sodium PDT is a potentially curative treatment in patients with early oesophageal carcinoma who may be unfit or unwilling to undergo major surgery.

PDT for Tis-T2N0 Oral Cavity and Oropharyngeal Malignancies

Objective To evaluate the efficacy of PHOTOFRIN-mediated photodynamic therapy (PDT) for treatment of diffuse ‘field cancerization’ and Tis-T2N0M0 squamous cell carcinoma (SqCCa) of the oral cavity and oral pharynx in patients not amenable to or that failed conventional head and neck treatment. Methods This is nonrandomized prospective study of 28 patients with field cancerization and early stage Tis-T2N0M0 squamous cell carcinoma of the oral cavity/oropharynx treated with PHOTOFRIN-mediated PDT. Intravenous PHOTOFRIN (porfimer sodium)(dose 2.0 mg/kg) was administered outpatient, followed 48–60 hours later by intraoperative photoactivation at 630nm via fiberoptic microlens surface delivery (surgical light dose 50–100 J/cm2). Results 21 of 27 patients (77%) have demonstrated complete remission (follow-up 1 month to 12 years). There were 5 patients that had partial remission with recurrence observed at 3, 3, 8, 22, and 23 months subsequently retreated with conventional therapy. All locally disease-free individuals were followed up between 1 to 144 months. 14 of the 21 patients in complete remission were disease-free for a period greater than 1 year following photodynamic therapy. Conclusions PHOTOFRIN-mediated photodynamic therapy can be used as a primary modality to treat Tis-T2N0 tumors of the oral cavity and oropharynx or for treatment for those that have failed prior surgery and/or radiation therapy. PDT allows for preservation of function and structure with absence of systemic toxicity, and patients may have multiple drug administrations and laser light retreatments for local disease control.