talaporfin and Carcinoma--Squamous-Cell

Recently, in Japan, a novel photosensitizer, talaporfin sodium was developed for the photodynamic therapies of various diseases including malignant tumors. At the same time, a diode laser device, Panalas 6405, to be used for this therapy was developed. Talaporfin was first extracted and refined from plant chlorophyll and was found that the skin photosensitivity caused by drug disappeared faster than the existing photosensitizer. Clinically, in the patients with early lung cancer, the complete response was obtained in 85.7% of the lesions (36/42 lesions) by the administration of 40 mg/m2 followed by laser irradiation at 100 J/cm2 4-6 hours later. The sensitivity disappeared mostly within 2 weeks.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dihematoporphyrin Ether; Humans; Laser Therapy; Lung Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins

Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that exhibits chemical purity, absorption at 664 nm wavelength and may be useful in photodynamic therapy (PDT).. This open label phase I clinical trial at the University of California, Davis Medical Center examined the pharmacokinetic properties of Npe6 and clinical response to PDT with this photosensitizer. A single intravenous dose of Npe6 was administered to 14 cancer patients with superficial malignancies (basal cell carcinoma = 22 lesions, squamous cell cancer = 13 lesions, papillary carcinoma = 14 lesions). Patients received one of five ascending doses (0.5 mg/kg (n = 4), 1.0 mg/kg (n = 3), 1.65 mg/kg (n = 3), 2.5 mg/kg (n = 3), or 3.5 mg/kg (n = 1)) 4-8 h prior to light activation. The total light dose (range 25-200 J/cm2) depended on the tumor shape and size. Light was delivered using an argon-pumped tunable dye laser. Serum NPe6 concentrations were measured over a 28-day period. The toxicity and cutaneous clinical efficacy of NPe6 were observed.. Four weeks post-PDT, 20 of 22 basal cell carcinoma tumors (91%) showed a complete response. Eighteen of 27 other malignant cutaneous tumors showed a complete (n = 15/27, 56%) or partial (n = 3/27, 11%) response. Fewer non-responders were seen at an Npe6 dose level of 1.65 mg/kg or higher. Only 2 of 14 patients experienced an adverse event that was definitely related to NPe6 administration. Photosensitivity resolved within 1 week of NPe6 dosing in 12 of 14 patients. Analysis of serum levels of 11 individual patients indicated that a two-compartment model with a residual phase best fits the data. The mean alpha, beta, and terminal half-lives were 8.63+/-2.92, 105.90+/-37.59 and 168.11+/-53.40 h (+/-1 SD), respectively. The observed mean volume of distribution was 5.94+/-2.55 l, and the mean clearance was 0.0394+/-0.0132 l/h. These values were independent of the dose administered.. The photosensitizer, NPe6, was well tolerated with minimal phototoxic side effects, and demonstrated preliminary efficacy against cutaneous malignancies.

Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Papillary; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin Neoplasms; Treatment Outcome

Photofrin is the most commonly used photosensitizer for photodynamic therapy (PDT). The major side effect of Photofrin is cutaneous photosensitivity. A second generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) has shown anti-tumor efficacy and rapid clearance from skin. Therefore, we conducted a phase II clinical study to investigate the anti-tumor effects and safety of NPe6 in patients with early superficial squamous cell carcinoma of the lung. Enrollment criteria consisted of endoscopically evaluated early stage lung cancer with normal chest X-ray and CT images, no lymph node or distant metastasis. Tumors were located no more peripherally than subsegmental bronchi, the peripheral margin had to visible, and the tumor size had to not more than 2 cm in diameter. The histologic type of the tumor had to squamous cell carcinoma. Laser irradiation (100 J/cm2) using a diode laser was performed at 4 h after administration of NPe6 (40 mg/m2). Among 41 patients with 46 lesions, 40 with 45 lesions were eligible for safety evaluation, and 35 patients with 39 lesions were judged as eligible for efficacy evaluation. No serious adverse drug reactions were observed. Disappearance of skin photosensitivity was recognized within 2 weeks in 28 of 33 patients (84.8%) and in all the other seven patients first tested at 15-18 days. Complete response (CR) was seen in 84.6% of lesions (82.9% of patients). This study demonstrated excellent anti-tumor effects and safety, especially low skin photosensitivity in patients with early stage lung cancer. PDT using the second generation photosensitizer NPe6 and a diode laser will likely become a standard modality of PDT for central type early superficial squamous cell carcinoma of the lung.

Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Lasers; Lung Neoplasms; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Safety; Salvage Therapy; Skin; Treatment Outcome

Talaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also be indicated for local recurrence or residue after the first salvage tPDT. However, the safety and efficacy of repeated tPDT have not been elucidated.. We reviewed 52 patients with esophageal cancer who were treated with the first tPDT at Kyoto University Hospital between October 2015 and April 2020.. Among 52 patients, repeated tPDT after the first tPDT was indicated for 13 patients (25%), of which six had residual tumor, four had local recurrence after complete response (CR) after the first tPDT at the primary site, and six had metachronous lesion. The total session of repeated tPDT was 25; 16 were for primary sites and nine were for metachronous sites. Among them, six patients (46.2%) achieved local (L)-CR and nine lesions (56.3%) achieved lesion L-CR. By session, 10 sessions (40%) achieved L-CR. There were no severe adverse events except for one patient; this patient showed grade 3 esophageal stenosis and perforation after the third tPDT on the same lesion that was previously treated with porfimer sodium photodynamic therapy four times.. Repeated tPDT could be an effective and safe treatment for local failure even after salvage tPDT for esophageal cancer.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Neoplasm Recurrence, Local; Photochemotherapy; Porphyrins

Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy and safety of salvage PDT using the second-generation photosensitizer, talaporfin sodium (L-PDT), and compare L-PDT to PDT using porfimer sodium (P-PDT).. We retrospectively analyzed clinical outcomes of patients treated with L-PDT and P-PDT. Patients with histologically proven local failure limited to the shallow muscularis propria layer (T2) after CRT or radiotherapy (RT) for esophageal cancer were enrolled.. A total of 121 patients were enrolled in this study. L-PDT and P-PDT groups consisted of 44 and 77 patients, respectively. The overall local complete response (L-CR) rate was 62.1% (95% confidence interval [CI], 52.6-70.9), and the L-PDT group showed a better L-CR rate than did the P-PDT group (69.0% [95% CI 52.9-82.4] vs. 58.1% [95% CI 46.1-69.5]). The common complications of skin phototoxicity, esophageal stricture, and esophageal fistula were all less frequent in the L-PDT group than in the P-PDT group. The only treatment-related death in this study was in the P-PDT group. With a median follow-up period of 15.8 months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1 year was significantly higher among patients who achieved L-CR (91.2% [95% CI 80.2-96.3]) than among those who could not achieve L-CR with PDT (50.8% [95% CI 33.6-65.6]).. L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Dihematoporphyrin Ether; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retrospective Studies; Salvage Therapy; Treatment Failure

To assess the effect of photodynamic therapy (PDT) with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma (SCC).. Eight patients who were diagnosed with oral SCC without any metastasis and underwent talaporfin sodium-mediated PDT (t-PDT) were included in this study. Biopsies were performed 4-6 weeks after t-PDT. The clinical response was evaluated using Response Evaluation Criteria in Solid Tumors.. Complete response (CR) was achieved in six of eight cases, and two cases showed partial response (PR) as a clinical outcome of t-PDT. Recurrence occurred in one of the CR cases 9 months after irradiation. The patient underwent tumor resection and no recurrence was found after surgery. The two cases with PR died from the cancer despite additional PDT.. t-PDT is an effective treatment strategy for oral SCC. Talaporfin sodium has an advantage with regard to early elimination from the body compared with porfimer sodium.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Lasers, Semiconductor; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Porphyrins

The innovation of thoracic interventions, such as endobronchial ultrasound and photodynamic ablation, has changed the interventional management of lung cancer. In this case report, we discuss the case of a successful treatment of endobronchial squamous cell carcinoma occluding the left upper lobe bronchus by a minimally invasive transbronchial approach. This case was initially planned for a sleeve left upper lobectomy. The careful assessment of radiological and ultrasonographic imaging concluded that the tumor was early-stage lung cancer. Multimodal endobronchial treatment cured the lung cancer without a thoracotomy. Pulmonary function was well preserved and no recurrence was found for more than 5 years. Even in the presence of a bulky endobronchial tumor, if there is no clear evidence of extraluminal invasion by computed tomography scan, a local bronchoscopic staging of the disease is mandatory.

Topics: Antineoplastic Agents; Bronchial Neoplasms; Bronchoscopy; Carcinoma, Squamous Cell; Humans; Male; Middle Aged; Photochemotherapy; Porphyrins; Ultrasonography, Interventional

Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.

Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; DNA Breaks, Double-Stranded; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Fluorescence; Humans; Intracellular Space; Mice; Photochemotherapy; Porphyrins; Reactive Oxygen Species; Reproducibility of Results

Patients with centrally located early lung cancer (CLELC) are often heavy smokers with a considerably high risk of multiple primary lung cancer (MPLC) lesions; treatment strategies for such patients must preserve the cardiopulmonary function.. Between July 2004 and July 2008, patients with CLELC underwent photodynamic therapy (PDT) using NPe6, second-generation photosensitizer at Tokyo Medical University Hospital. Among these patients, we retrospectively analyzed MPLC, which was treated by surgery plus PDT or PDT alone and examined the effectiveness of PDT, and we propose a treatment strategy for patients with MPLC.. A total of 64 patients with CLECL received NPe6-PDT, and MPLCs were found in 22 patients (34.4%) using sputum cytology and a bronchoscopical examination using autofluorescence bronchoscopy. Among these 22 patients, 10 patients underwent surgery for primary lung cancer and underwent NPe6-PDT for the treatment of secondary primary CLELC, one patient underwent PDT for CLELC as a primary lesion followed by an operation for peripheral-type lung cancer as a secondary primary lesion, and 11 patients underwent PDT alone for MPLC lesions (28 lesions) that were roentgenographically occult lung cancers. Among these 22 patients with MPLC including peripheral-type lung cancers, which were resected by surgery, all 39 CLELC lesions exhibited a complete response after PDT, and all patients were alive.. For patients with lung cancer with a long-term history of smoking, careful follow-up examinations after surgical resection are needed considering the incidence of metachronous primary lung cancers. PDT can play an important role for the treatment strategy for MPLC.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Lasers; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Photochemotherapy; Photosensitizing Agents; Pneumonectomy; Porphyrins; Prognosis; Retrospective Studies; Smoking; Survival Rate; Tokyo

Photodynamic therapy (PDT) is a method for treating pre-cancerous and cancerous lesions of the skin, bladder and oral cavity. However, tumour recurrence after PDT remains problematic despite good initial response. Some studies have shown that PDT induces vascular endothelial growth factor (VEGF) expression in human oral squamous cell carcinoma and other organs. However, little is known about VEGF expression applied to PDT in human carcinoma cell lines. No studies have been conducted of PDT using Npe6 (Npe6-mediated PDT), a second-generation photosensitizer, in the human oral carcinoma cell line, HSC-3 cells. We investigated the expression of VEGF, c-jun and c-fos proto-oncogenes in HSC-3 cells in response to Npe6-mediated PDT. We also addressed the possibility that oxidative damage induced by PDT could lead to an angiogenic response, via VEGF expression. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that Npe6-mediated PDT induced the expression of mRNAs for VEGF, c-jun and c-fos in time- and concentration-dependent manners. Desferrioxamine (DFX), an iron chelator, induced VEGF expression, but the expression pattern was different to that of Npe6-mediated PDT. The expression mRNAs for VEGF, c-jun and c-fos induced by Npe6-mediated PDT were inhibited by SB203580, p38 MAPK inhibitors, and the expression of VEGF mRNA was inhibited by cycloheximide (CHX), a protein synthesis inhibitor. The c-jun mRNA expression was inhibited, whereas the c-fos mRNA expression was enhanced by N-acetyl-L-cysteine (NAC), a free radical scavenger. We conclude that Npe6-mediated PDT induces the expression of VEGF, c-jun and c-fos in human oral carcinoma cell line, HSC-3 cell, and at least partly, through the activation of p38 MAPK.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cycloheximide; Deferoxamine; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Free Radical Scavengers; Genes, fos; Genes, jun; Humans; Imidazoles; Mouth Neoplasms; p38 Mitogen-Activated Protein Kinases; Photochemotherapy; Photosensitizing Agents; Porphyrins; Protein Synthesis Inhibitors; Pyridines; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Siderophores; Vascular Endothelial Growth Factor A

Mono-L-aspartyl chlorin e6 (NPe6) is an effective photosensitizer with a major absorption band at 664 nm. NPe6 is potentially exploitable for photodynamic therapy (PDT) and does not cause the side effect of prolonged normal skin photosensitization. However, there are no clinical and experimental reports of its use in oral cancer till now. In the present study, we examined the effectiveness of NPe6-induced PDT with a diode laser for treatment of tongue cancer in the nude mouse. Six nude mice with experimental tongue cancer (HSC-3) were given 10 mg/kg NPe6 intravenously. Two hours later PDT was performed using a laser diode at a light dose of 100 J/cm2 and wavelength of 664 nm. Histological changes in the tumors were examined 42-72 h after PDT. Almost all of the tumors developed necrosis, while viable-like neoplastic cells remained mainly in the peripheral region of the tumor in some cases. The mean depth of necrosis below the surface was 2.1 mm. The mean tumor thickness below the surface was 2.3 mm. Tumor thickness coincided with the depth of necrosis. NPe6-induced PDT exhibited tumor selectivity and can effectively cause necrosis of tongue cancers. This therapy could be suggested for treatment of other superficial oral cancer.

Topics: Animals; Carcinoma, Squamous Cell; Female; Laser Therapy; Mice; Mice, Inbred BALB C; Mice, Nude; Necrosis; Photochemotherapy; Photosensitizing Agents; Porphyrins; Tongue Neoplasms

We have been engaged in basic and clinical research on photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25 years.. PDT for 264 centrally located early-stage lung cancer lesions yielded an initial complete response (CR) rate of 84.8%. PDT is now becoming a standard option for centrally located stage 0 (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for elderly patients in poor physical condition.. Recent results of interstitial PDT for peripheral-type lung cancers suggest that it may be a promising local curative treatment modality for lesions less than 1.0 cm in diameter.. In this article, we introduce our recent clinical trials of PDT for lung cancers (both central and peripheral), and new techniques of PDD in sentinel node navigation biopsy for breast cancers. Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT.

Topics: Adult; Aged; Aged, 80 and over; Animals; Breast Neoplasms; Carcinoma, Squamous Cell; Dihematoporphyrin Ether; Female; Humans; Japan; Lung Neoplasms; Male; Methicillin Resistance; Mice; Middle Aged; Neoplasm Recurrence, Local; Patient Selection; Photochemotherapy; Photosensitizing Agents; Porphyrins; Sentinel Lymph Node Biopsy; Staphylococcal Infections; Staphylococcus aureus

We observed real-time spectral images using line-scan imaging spectrography in order to evaluate tumor viability.. Japanese albino rabbits, which underwent the implantation of VX2 tumor strain, were used as subcutaneous tumor models (n = 54). Photodynamic therapy (PDT) consisted of semiconductor laser irradiation of the tumorous lesion. The experimental groups consisted of a PDT group (n = 15) and a non-PDT group (control group, n = 15). The spectral images taken by a CCD camera underwent computer processing. Next, the spectrum of the tumorous lesion was observed and the peak spectrum value was measured.. Two peaks (545 and 575 nm) corresponding to the absorbance spectrum of oxygenated hemoglobin (oxyHgb) were observed in the untreated area. In the treated area, however, they disappeared and a different peak (560 nm) corresponding to the absorbance spectrum of deoxygenated hemoglobin was observed. PDT induced ischemic tissues and the cells could be confirmed in real time in vivo in monochrome and color images reflecting the oxyHgb amount. A histopathological examination and phosphotungstic acid hematoxylin staining demonstrated diffuse fibrin accumulation in the microvessels, while proliferating cell nuclear antigen staining showed a reduced nuclear stainability.. These results demonstrated that the real-time spectral images showed the actual histological conditions such as a blocked tumor blood flow and reduced tumor viability.

Topics: Animals; Carcinoma, Squamous Cell; Disease Progression; Male; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Porphyrins; Rabbits; Skin Neoplasms; Spectrophotometry; Treatment Outcome