Efficacy and safety of HpD-PDT for Extramammary Paget's Disease refractory to conventional therapy: A prospective, open-label and single arm pilot study.

BACKGROUND: Extramammary Paget's Disease (EMPD) is an intraepithelial cancer that is prone to recurrence and sometimes refractory to therapy. A few EMPD cases have been treated with Photodynamic therapy (PDT), which reported high complete remission (CR) rates and low recurrence with hematoporphyrin derivatives (HpD) The aim of this study was to further explore the efficacy and safety of HpD-PDT for EMPD patients. METHODS: Open-label, single arm, pilot study was designed to investigate the role of HpD-PDT in EMPD. The HpD sensitizer was given intravenously at a dose of 3 or 5 mg/kg 48 h before light irradiation with a laser 630 nm red light at a dose level of 150-200 J/cm2. Clinical parameters involving gender, age, disease course, previous treatment, tumor thickness, long diameter of lesion, TNM staging, EMPD staging, HpD dosage, Visual Analogue Scale (VAS) score, 1st month visit result, subsequent treatment, follow up period and endpoint outcomes were collected to evaluate efficacy and safety of the intervention. RESULTS: Eleven patients with pathologic confirmed EMPD were treated with HpD-PDT. The thickness of skin lesions which were located in vulva, penis, scrotum, and perianal area is 0.8∼6.7 mm (mean thickness 2.9 mm). All patients were followed up for an average of 17.4 months (12∼27 months). Complete remission (CR) rate and partial remission (PR) rate at the 1st month were 90.1% (10/11) and 9.1% (1/11) respectively. At the end of follow-up, 72.7% of the subjects (8/11) showed CR. Pain, infection, photosensitivity and uroschesis are recorded as adverse events (AEs) in this population, and no event of hepatic impairment was reported. After treatment, all the eleven patients showed different degrees of scar in the treatment site, but none of them had any structural or functional abnormalities. CONCLUSIONS: According to our study, HpD-PDT in EMPD is able to offer acceptable disease outcomes including relatively high CR rate, with good cosmetic and functional outcomes, and could be considered a potential recommended therapy for patients with EMPD. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR-1900024965).

Efficacy and safety of photodynamic therapy with temoporfin in curative treatment of recurrent carcinoma of the oral cavity and oropharynx.

Therapeutic options for recurrent carcinoma of the upper aérodigestive tract (UADT) are limited. The prognosis of these tumours remains poor with significant rate of recurrence and a lower median survival time. Photodynamic therapy (PDT) is a relatively new therapeutic alternative which combines the use of a photosensitising agent and light to induce a cytotoxic effect on the tissues. This is a retrospective single-centre study carried out in patients with a recurrence of an oral cavity or oropharyngeal carcinoma or a second appearance of tumour in a previously irradiated area. There were no metastases in lymph nodes or other organs. Laser treatment was carried out 96 h after temoporfin (Foscan(®)) injection. In our series we had 14 cases with a complete response, 1 partial response. Overall survival at 1 year was 72 % and 36 % at 5 years. Disease-specific survival at 1 year was 82 % and 45 % at 5 years. Recurrence-free survival at 1 year was 52 % and 34 % at 5 years. Side effects mainly described are pain in the area of illumination, well controlled. PDT with Foscan(®) gives useful results in terms of survival and improvement in quality of life with few adverse events or severe complications. The fact that it has low toxicity and that treatment sessions can be repeated mean it should be considered in the therapeutic armamentarium for recurrent carcinoma of the UADT.

Efficacy and safety of hemoporfin in photodynamic therapy for port-wine stain: a multicenter and open-labeled phase IIa study.

BACKGROUND/PURPOSE: This phase IIa study aimed to study the efficacy and safety of hemoporfin in photodynamic therapy (PDT) with a 532 nm continuous laser for port-wine stain (PWS). METHODS: In this 8-week open-labeled study in three centers, three different laser exposure times (532 nm continuous laser for 20, 30 and 40 min) were used in stage I, group A, stage II, group B and stage III, group C, respectively. Primary efficacy assessment was performed by an independent group of experts, who reviewed the standardized photos. Secondary efficacy assessment consisted of the subjective grading of the PWS fading by the investigators and the patients. Treatment reactions and adverse events (AE) were recorded separately. RESULTS: Forty patients were initially enrolled in the study, but stage III had to be cancelled eventually for the safety of the patients. Patients in groups A and B showed similar satisfactory results in efficacy assessments, the total 'response' rate being 80.0% and 94.7% in groups A and B, respectively. The AE rates were also similar in the two groups. Self-limiting photosensitive dermatitis and hyperpigmentation were the most frequently observed AE. CONCLUSION: Hemoporfin-PDT is effective and safe for patients with PWS aged 16-50.

Drug-induced photosensitivity.

(1) Photosensitivity reactions are cutaneous disorders due to exposure to ultraviolet (UV) radiation of natural or artificial origin. They occur or are more prevalent on unprotected skin. The main clinical manifestations are burns, eczema-like rash, urticaria, pigmentation, or onycholysis; (2) Many drugs increase cutaneous sensitivity to UV, sometimes for therapeutic purposes, but it is generally an unwanted effect.

The attenuation effect of 3,4-dihydroxy-phenyl lactic acid and salvianolic acid B on venular thrombosis induced in rat mesentery by photochemical reaction.

3,4-dihydroxy-phenyl lactic acid (DLA) and salvianolic acid B (SAB) are two major water-soluble components of Salvia miltiorrhiza (SM). Previous works have revealed the ability of DLA and SAB to scavenge oxygen free radicals, inhibiting the expression of adhesion molecules CD11b/CD18 in neutrophil. Cardiotonic pills (CP), which is a traditional Chinese medicine compound preparation containing DLA and SAB, was found to inhibit venular thrombosis induced by photochemical reaction (PR) in rat mesentery. The present study addressed the effect of DLA and SAB on PR-induced thrombosis in rat mesentery by utilizing a microcirculation dynamic viewing system. The result demonstrated that both DLA and SAB delayed thrombus-initiation time, while DLA also prolonged thrombus half-size time. The experiments explored the mechanism underlying that the dihydrorhodamine 123 (DHR) fluorescence in the mesenteric venular walls after PR challenge was diminished by pretreatment with either DLA or SAB, the expression of CD18 in neutrophils elicited by PR was depressed by administration of DLA, while mast cell degranulation in rat mesentery induced by PR was damped by SAB. The antioxidant potential of the two substances is likely to be responsible for their most beneficial effects on thrombosis, through either directly scavenging the peroxides produced and/or indirectly depressing the expression of adhesion molecules in neutrophil.

Optimization of light dosimetry for photodynamic therapy of Barrett's esophagus: efficacy vs. incidence of stricture after treatment.

BACKGROUND: Photodynamic therapy (PDT) may be used to ablate high-grade dysplasia/early stage cancer (HGD/T1) in patients with Barrett's esophagus. PDT may result in esophageal stricture. This nonrandomized, unblinded, dose de-escalation study in consecutive patients was designed to determine the lowest light dose effective for ablation of HGD/T1 while reducing the incidence of stricture. METHODS: A total of 113 patients received an injection of porfimer sodium (2 mg/kg). Three days later, 630 nm light was delivered by using a 20-mm-diameter PDT balloon at doses of 115 J/cm (n=59), 105 J/cm (n=18), 95 J/cm (n=17), or 85 J/cm (n=19). Treatment efficacy was determined by obtaining biopsy specimens of the treated area 3 months later. The incidence of stricture was determined by the need for esophageal dilation to treat dysphagia. A stricture was considered severe if 6 or more dilations were required. RESULTS: The incidence of severe stricture was related to the light dose. At 115 J/cm, 15.3% of patients developed severe strictures compared with 5.3% to 5.6% of those treated with the lower doses. At a light dose of 115 J/cm, 17.0% of patients had residual HGD/T1. Light doses of 105 J/cm, 95 J/cm, and 85 J/cm resulted in residual HGD/T1 in 33.3%, 29.4%, and 31.6% of patients, respectively. None of the observations were statistically significant. CONCLUSIONS: Decreasing the light dose below 115 J/cm appeared to result in a reduced incidence rate of severe stricture but higher relative frequencies of residual HGD/T1 in Barrett's esophagus.

Photodynamic therapy for cholangiocarcinoma.

The prognosis of perihilar cholangiocarcinoma (CC) is limited by tumor spread along the biliary tree leading to refractory obstructive cholestasis, cholangitis, and liver failure. Palliation with biliary endoprostheses yields median survival times between 4 and 6 months for nonresectable CC. Tumor ablation with photodynamic therapy (PDT) combined with biliary stenting reduces cholestasis and significantly improves median survival time to 11.5 to 16.2 months. PDT with porfimer and laser light of 630 nm provides tumoricidal tissue penetration to a depth of only 4 to 4.5 mm that does not eradicate most tumors. Time to progression lasts approximately 6 months; in other words, PDT is required twice annually. PDT costs less and enhances quality of life and survival time as compared with chemotherapy for metastatic colon cancer. These data suggest that PDT should be offered as part of the palliative treatment of CC in hepatobiliary referral centers.

Phase II trial of pleural photodynamic therapy and surgery for patients with non-small-cell lung cancer with pleural spread.

PURPOSE: Non-small-cell lung cancer (NSCLC) with pleural spread is incurable, with median survival rates ranging from 6 to 9 months. Surgery alone fails to locally control this disease or extend survival beyond the accepted treatment, palliative chemotherapy. METHODS: We conducted a phase II trial to evaluate the effects on local control and survival of combining surgery with intraoperative photodynamic therapy (PDT), a light-based cancer treatment, in patients with NSCLC with pleural spread. Patients received porfimer sodium (2 mg/kg), 24 hours before surgery, at which time all gross tumor was resected and followed by illumination of the hemithorax with 630 nm light to a measured dose of 30 J/cm(2). Photosensitizer levels in tumor and surrounding normal tissue were measured. RESULTS: Twenty-two patients with NSCLC were enrolled; 17 underwent complete debulking and PDT, three underwent partial debulking/PDT, and two patients were unresectable. Local control of pleural disease at 6 months was achieved in 11 of 15 (73.3%; 95% CI, 44.9% to 92.2%) assessable patients. Median overall survival for all 22 patients was 21.7 months (95% CI, 17.7 to 25.8 months). Measured levels of porfimer sodium in tumor were greater than those measured in normal tissues, with ratios ranging from 1.19 to 22.42. CONCLUSION: Our results indicate surgery and PDT can be performed safely with very good local control. The median survival of 21.7 months, calculated from the time of surgery and PDT is encouraging. Further evaluation of this therapy is warranted.

A phase I study of Foscan-mediated photodynamic therapy and surgery in patients with mesothelioma.

BACKGROUND: Photodynamic therapy (PDT) is a light-based cancer treatment that, in the correct setting, can be delivered intraoperatively as an adjuvant therapy. A phase I clinical trial combining surgical debulking with Foscan-mediated PDT was performed in patients with malignant pleural mesothelioma. The purpose of the study was to define the toxicities and to determine the maximally tolerated dose (MTD) of Foscan-mediated PDT. METHODS: A total of 26 patients completed treatment. Tumor debulking was accomplished with either an extrapleural pneumonectomy (7 patients) or a lung-sparing pleurectomy-decortication (19 patients). Patients were injected with Foscan before surgery, and 652 nm light was delivered intraoperatively after completion of surgical debulking. Four light sensors were placed in the chest, allowing delivery of light to a uniform measured dose throughout the hemithorax. RESULTS: Four dose levels were explored. The MTD was 0.1 mg/kg of Foscan injected 6 days before surgery in combination with 10 J x cm(-2) 652 nm light. Dose limiting toxicity at the next higher dose was a systemic capillary leak syndrome leading to death in 2 of 3 patients treated at that dose. Other PDT-related toxicities included wound burns and skin photosensitivity. In all, 14 patients were treated at the MTD without significant complications. CONCLUSIONS: Foscan-mediated PDT can be safely combined with surgery at the established MTD. Unlike most other surgery-based multimodal treatments for mesothelioma, Foscan-mediated PDT affords the option, in selected patients, of accomplishing tumor debulking with a lung-sparing procedure rather than an extrapleural pneumonectomy. A phase II study is warranted.

Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors.

BACKGROUND AND OBJECTIVE: The primary goal was to determine the maximal tolerable light dose that can be administered to patients undergoing multifiber interstitial photodynamic therapy (PDT) of malignant brain tumors at a fixed dose of photosensitizer. STUDY DESIGN/MATERIALS AND METHODS: Eighteen patients (12 glioblastomas, 5 anaplastic astrocytoma, and 1 malignant ependymoma) were included in this study. The total light dose delivered to the tumor was divided into three groups of six patients each: 1,500-3,700 J, 3,700-4,400 J, and 4,400-5,900 J. RESULTS: Five patients (all glioblastomas) demonstrated postoperative permanent neurologic deficits. None of the patients in 1,500-3,700 J, two patients in 3,700-4,400 J, and three patients in 4,400-5,900 J had neurologic deficits. Glioblastomas recurred more often than anaplastic astrocytomas. Increasing the light dose did not make a difference in local/regional control of glioblastomas. Patients with anaplastic astrocytomas survived (mean, 493 days) longer than patients with glioblastomas (mean, 116.5 days) after PDT. Four patients had prolonged survival (more than a year) after PDT. CONCLUSIONS: Increasing the total light dose delivered to the tumor increases the odds of having a permanent neurologic deficit but does not increase survival or time to tumor progression. There was no difference in local or marginal recurrence with increasing light dose. Recurrent anaplastic astrocytomas tend to do better than recurrent glioblastomas with PDT.

Photodynamic therapy for treatment of malignant dysphagia.

Photodynamic therapy (PDT) was recently approved by the Food and Drug Administration for palliating obstructing esophageal cancer. This report reviews our initial experience using PDT to treat malignant dysphagia. Patients with inoperable, obstructing esophageal cancer were considered for PDT. Photofrin was injected 48 hours before endoscopic laser activation. Dysphagia score was assessed. Thirty patients underwent 53 PDT courses. Improvement in dysphagia occurred in 83%. Mean dysphagia score decreased from 2.8 to 1.8 (p < 0.05). Complications included esophageal stricture (9.4%), candida esophagitis (5.7%), symptomatic pleural effusion (5.7%), contained esophageal perforation (1.9%), aspiration pneumonia (1.9%), and sunburn (13.2%). Seventeen patients (57%) required more than one PDT treatment, and in 10 an expandable metal stent was used as an adjunct. The 30-day mortality rate was 7%. PDT is effective in palliating patients with malignant dysphagia. The ideal patient for PDT has an obstructing, primarily endoluminal esophageal tumor with minimal extrinsic compression.

Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long-term experience.

INTRODUCTION AND OBJECTIVE: Photodynamic therapy (PDT) combines a photosensitizer such as Photofrin with red laser light (630 nm) to destroy cancer cells. Investigators have reported effectiveness of PDT in the management of patients with recurrent superficial bladder cancer. We retrospectively reviewed our experience in 58 patients to assess the long-term role of PDT in the management of resistant superficial transitional cell carcinoma (TCC) including Ta, T1, and refractory carcinoma in situ (CIS) of the urinary bladder. MATERIALS AND METHODS: All 58 patients had failed at least one course of standard intravesical therapy or had contraindication for intravesical chemo- or immunotherapy. Patients with malignancy present (Ta-T1/Grade I-III, CIS) were accepted for ablative PDT. Patients undergoing prophylactic PDT after complete resection were confirmed to be tumor-free by cystoscopy and bladder was cytology before PDT. Post-PDT evaluations included weekly telephone contact to assess acute adverse reactions and assessment of efficacy and bladder toxicity at three months and quarterly thereafter. RESULTS: These 58 patients underwent a single PDT treatment with 2.0 or 1.5 mg/kg of Photofrin and 10-60 J/cm2 light (630 nm). At three months, complete response rates were 84% and 75% for residual resistant papillary TCC and refractory CIS respectively; and 90% of patients treated prophylactically had not had recurrences. At a median followup of 50 months (range 9-110), 59% (34/58) of the responders are alive, with 31/34 still disease-free. CONCLUSION: PDT using 1.5 mg/kg of Photofrin and 15 J/cm2 of light (630 nm) should be considered a safe and effective treatment for refractory CIS or recurrent papillary TCC.

Damage to tumour and brain by interstitial photodynamic therapy in the 9L rat tumour model comparing intravenous and intratumoral administration of the photosensitiser.

In the 9L rat brain tumour model the damage to tumour and normal brain by photodynamic therapy after intratumoural photosensitizer administration (intratumoural PDT) was studied. Twenty four rats received an intratumoural injection of 4 or 40 mm3 haematoporphyrin derivative (HpD, 5 mg ml-1), followed by interstitial irradiation with 20 Joule (J) (630 nm) 5 h later. For comparison, seven rats were treated with 20 Joule 24 h after an intravenous injection of 10 mg kg-1 HpD (intravenous PDT). With the chosen PDT parameters there was no important difference between the damaged areas produced by intratumoural PDT or intravenous PDT. No selective tumour kill was observed. Even though normal brain tissue was heavily damaged, vital tumour parts were still present. Intravenous PDT caused extensive diffuse damage to small blood vessels in tumour and surrounding normal brain. Intratumoural PDT was characterised by an infiltration of polymorphonuclear cells into damaged tissue, dilatation of larger blood vessels and gross haemorrhage. These results suggest an immediate vascular shutdown in the intravenous approach, while in the intratumoural approach the vasculature remained patent initially. Because of the severe side effects observed, the use of HpD seems not advisable for intratumoural PDT of brain tumours.

Mono-L-aspartyl chlorin e6 (NPe6) and hematoporphyrin derivative (HpD) in photodynamic therapy administered to a human cholangiocarcinoma model.

BACKGROUND: Despite their relatively localized nature, the therapy for surgically unresectable cholangiocarcinomas has been largely unsuccessful. Photodynamic therapy is a promising technique for both curative and palliative treatment of this malignancy. The effectiveness of a potential new photosensitizer, mono-l-aspartyl chlorin e6 (NPe6), was compared with that of a traditional drug, hematoporphyrin derivative (HpD), in photodynamic therapy administered to a human cholangiocarcinoma model. METHODS: An established cholangiocarcinoma cell line was inoculated subcutaneously in the left back of male nude mice age 8 weeks. After a predetermined tumor size was reached, the mice were randomly assigned to either a control group or an experimental group. Experimental tumor-bearing mice received either HpD (5 mg/kg or 10 mg/kg) or NPe6 (2 mg/kg, 5 mg/kg, or 8 mg/kg) followed by photoradiation. HpD and NPe6 were administered intraperitoneally at 24 and 2 hours, respectively, prior to light exposure. Photoradiation was conducted using a xenon-mercury arc lamp with a 405-650 nm filter at a light flux of 80 J/cm2. Tumor response was assessed by serial tumor volume measurements. RESULTS: Control mice showed an estimated mean tumor volume doubling rate of 9.0 days. Triaxial tumor measurements correlated well with autopsy measurements (correlation coefficient = 0.9). Overall differences in tumor volume reduction were detected (P < 0.001) among the three groups: HpD, NPe6, and controls (photoradiation only, HpD only, or NPe6 only). The degree of tumor volume reduction was superior for dosages of NPe6 compared with all dosages of HpD (P < 0.05). Although a dose effect was detected (P < 0.05) for HpD and separately for NPe6, a consistent dose-response relationship was not observed for either. Inhibition of tumor regrowth was better for NPe6 compared with HpD. The depth of tissue injury was significantly increased (P < 0.05), by 67%, for 5-8 mg/kg of NPe6 compared with 5-10 mg/kg of HpD. The duration of cutaneous photosensitization was also decreased for NPe6 compared with HpD. CONCLUSION: Photodynamic therapy with HpD or NPe6 was effective inducing tumor regression in the cholangiocarcinoma model in this study. At the dosages studied, NPe6 appeared to induce greater tumor regression than HpD, with decreased tumor regrowth and duration of cutaneous photosensitization.

Photodynamic therapy for early stage squamous cell carcinoma of the lung.

OBJECTIVE: To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung. MATERIAL AND METHODS: A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT. RESULTS: A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116). CONCLUSION: On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.

Photodynamic therapy in Barrett's esophagus.

OBJECTIVES: This report presents clinical results using photodynamic therapy for dysplasia and superficial esophageal cancer in Barrett's esophagus. METHODS: Forty-five (45) patients with Barrett's esophagus and dysplasia were treated with photodynamic therapy using sodium porfimer 2.0 mg/kg as the photosensitizing drug. Fifteen patients also had 16 superficial esophageal cancers (0-1.5 cm; Tis-T2, N-0, M-0). Red light (630 nm) was delivered to the esophageal mucosa by a diffuser inserted through the endoscope or via a windowed esophageal centering balloon designed to improve targeted delivery of light during photodynamic therapy. Patients were maintained on omeprazole and were followed for 6-62 months following photodynamic therapy. RESULTS: Photodynamic therapy produced mucosal damage in treated areas. Ablation of dysplastic or malignant mucosa was followed by healing and conversion of approximately 75-80% of treated Barrett's mucosa to normal squamous epithelium in all patients. Complete elimination of Barrett's epithelium was found in 16 patients. Areas of dysplasia were eliminated in 35 of the 45 patients. All 16 malignancies were ablated. No cancer recurrence was found in follow-up. Healing was associated with esophageal strictures in 58%, which were treated successfully by esophageal dilation in all patients. CONCLUSION: Photodynamic therapy combined with long-term acid inhibition provides an effective endoscopic therapy to (1) eliminate Barrett's mucosal dysplasia and superficial esophageal cancer and (2) reduce the amount of and, in some cases, eliminate Barrett's mucosa.

A preliminary pharmacokinetic study of intravenous Photofrin in patients.

Photofrin is a light-activated compound used for photodynamic therapy (PDT) of malignant tumors. Although PDT with this drug has been approved for clinical use in the United States, Canada, Japan, and the Netherlands there are few published reports on the biodistribution of Photofrin in humans. In this study we report measurable amounts of Photofrin in human serum up to approximately 1 year following injection of two different Photofrin doses. Concentration-time data were collected from 3, 12, 19, and 10 patients after 0.75, 0.875, 1, and 2 mg Photofrin/kg body weight. Patients who received 2 mg Photofrin/kg were scheduled to undergo intraoperative PDT for the treatment of mesothelioma or carcinoma of the lung. Patients receiving 0.75, 0.875, or 1 mg Photofrin/kg were treated for basal cell carcinoma; 1 mg Photofrin/kg is now a standard dose for PDT of cutaneous malignancies at this institute. For the 1 mg Photofrin/kg dose, a triexponential 3-compartment pharmacokinetic model was fitted to 30 data points pooled from the 19 patients, as if we had one "superpatient." The alpha, beta, and gamma halflives were approximately 16 h, 7.53 days, and 155.56 days, respectively. The mean (+/- SEM) serum concentrations 48 after injection (when most tumors are exposed to drug-activating light) of 0.875, 1, or 2 mg Photofrin/kg were 2.70 +/- 0.47, 4.00 +/- 0.66, and 3.47 +/- 0.97 micrograms Photofrin/ml, respectively. No porphyrin fluorescence could be detected in serum collected from patients 560 to 1335 days after Photofrin injection.

Bronchoesophagopleural fistula after photodynamic therapy for malignant mesothelioma.

A 66-year-old woman presented with a bronchoesophagopleural fistula 10 weeks after thoracic photodynamic therapy for malignant mesothelioma. This is the third reported case of an esophagopleural fistula developing subsequent to photodynamic therapy for mesothelioma. We review the literature on this topic and report our successful management of this complication.

Chemical modification of normal tissue damage induced by photodynamic therapy.

One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses.