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Expert Opinion on Pharmacotherapy Jan 2010Despite therapeutic advances, cancer remains the cause of an estimated 23% of deaths in the USA. New treatments for malignancy are greatly needed. (Review)
Review
IMPORTANCE OF THE FIELD
Despite therapeutic advances, cancer remains the cause of an estimated 23% of deaths in the USA. New treatments for malignancy are greatly needed.
AREAS COVERED IN THIS REVIEW
Talaporfin sodium is a light-activated drug that causes tissue death through induction of apoptosis. Systemic antitumor effects mediated by CD8(+) T cells have been demonstrated in preclinical studies, providing a mechanism for distant response of tumors noted in clinical trials. Talaporfin sodium is approved in Japan for early-stage endobronchial cancer. Phase I and II studies in solid tumors have shown tumor regression in patients refractory to other therapies. Phase III pivotal studies against hepatocellular carcinoma as monotherapy and liver-metastatic colorectal cancer in combination with chemotherapy are ongoing. Talaporfin sodium is also in studies in men with symptomatic benign prostatic hyperplasia. Substantial safety data from clinical trials so far indicate that the drug is well tolerated.
WHAT THE READER WILL GAIN
Talaporfin sodium has a broad safety profile and a mode of action that could affect growth in treated and untreated tumors.
TAKE HOME MESSAGE
Clinical and preclinical studies indicate that talaporfin sodium treatment may offer a powerful option to synergize current therapies, as well as an alternative monotherapy in treating cancer.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Cancer Vaccines; Carcinoma, Hepatocellular; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Combined Modality Therapy; Humans; Japan; Liver Neoplasms; Male; Neoplasm Staging; Neoplasms; Oxides; Porphyrins
PubMed: 20001435
DOI: 10.1517/14656560903463893 -
Journal of Clinical Medicine Jun 2021Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional... (Review)
Review
Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional treatment modalities in clinical practice because of the high frequency of cutaneous phototoxicity and esophageal stricture after the procedure. The second-generation photosensitizer, talaporfin sodium, which features more rapid clearance from the body, was developed to reduce skin phototoxicity, and talaporfin sodium can be excited at longer-wavelength lights comparing with a conventional photosensitizer. Endoscopic PDT using talaporfin sodium was initially developed for the curative treatment of central-type early lung cancer in Japan, and was approved in the early 2000s. After preclinical experiments, PDT using talaporfin sodium was investigated for patients with local failure after chemoradiotherapy, which was the most serious unmet need in the practice of esophageal cancer. According to the favorable results of a multi-institutional clinical trial, PDT using talaporfin sodium was approved as an endoscopic salvage treatment for patients with local failure after chemoradiotherapy for esophageal cancer. While PDT using talaporfin sodium is gradually spreading in clinical practice, further evaluation at the point of clinical benefit is necessary to determine the importance of PDT in the treatment of esophageal cancer.
PubMed: 34202917
DOI: 10.3390/jcm10132785 -
Spatiotemporal metabolic dynamics of the photosensitizer talaporfin sodium in carcinoma and sarcoma.Cancer Science Feb 2021Photodynamic therapy (PDT) using the photosensitizer talaporfin sodium (talaporfin) is a new mode of treatment for cancer. However, the metabolic mechanism of talaporfin...
Photodynamic therapy (PDT) using the photosensitizer talaporfin sodium (talaporfin) is a new mode of treatment for cancer. However, the metabolic mechanism of talaporfin has not been clarified. Thus, we investigated the uptake, transportation, and elimination mechanisms of talaporfin in carcinoma and sarcoma. The results showed that talaporfin co-localized in early endosomes and lysosomes. Talaporfin uptake was via clathrin- and caveolae-dependent endocytosis and a high amount of intracellular ATP was essential. Inhibition of lysosomal enzymes maintained intracellular talaporfin levels. Inhibition of K-Ras signaling reduced talaporfin uptake in carcinoma and sarcoma cell lines. Talaporfin was taken up by clathrin- and caveolae-dependent endocytosis, translocated from early endosomes to lysosomes, and finally degraded by lysosomes. We also demonstrated that ATP is essential for the uptake of talaporfin and that activation of K-Ras is involved as a regulatory mechanism. These results provide new insights into the metabolism of talaporfin in cancer cells for the enhancement of PDT for carcinoma and sarcoma.
Topics: Carcinoma; Cell Line, Tumor; Humans; Photosensitizing Agents; Porphyrins; Sarcoma
PubMed: 33190360
DOI: 10.1111/cas.14735 -
Cancers Aug 2020Photodynamic therapy (PDT) is an attractive cancer treatment modality. Talaporfin sodium, a second-generation photosensitizer, results in lower systemic toxicity and...
Photodynamic therapy (PDT) is an attractive cancer treatment modality. Talaporfin sodium, a second-generation photosensitizer, results in lower systemic toxicity and relatively better selective tumor destruction than first-generation photosensitizers. However, the mechanism through which PDT induces vascular shutdown is unclear. In this study, the in vitro effects of talaporfin sodium-based PDT on human umbilical vein endothelial cells (HUVECs) were determined through cell viability and endothelial tube formation assays, and evaluation of the tubulin and F-actin dynamics and myosin light chain (MLC) phosphorylation. Additionally, the effects on tumor blood flow and tumor vessel destruction were assessed in vivo. In the HUVECs, talaporfin sodium-based PDT induced endothelial tube destruction and microtubule depolymerization, triggering the formation of F-actin stress fibers and a significant increase in MLC phosphorylation. However, pretreatment with the Rho-associated protein kinase (ROCK) inhibitor, Y27632, completely prevented PDT-induced stress fiber formation and MLC phosphorylation. The in vivo analysis and pathological examination revealed that the PDT had significantly decreased the tumor blood flow and the active area of the tumor vessel. We concluded that talaporfin sodium-based PDT induces the shutdown of existing tumor vessels via the RhoA/ROCK pathway by activating the Rho-GTP pathway and decreasing the tumor blood flow.
PubMed: 32825648
DOI: 10.3390/cancers12092369 -
Esophagus : Official Journal of the... Oct 2021Talaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also...
BACKGROUND
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.
METHODS
We reviewed 52 patients with esophageal cancer who were treated with the first tPDT at Kyoto University Hospital between October 2015 and April 2020.
RESULTS
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.
CONCLUSION
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
PubMed: 34106353
DOI: 10.1007/s10388-021-00853-x -
No Shinkei Geka. Neurological Surgery May 2021Glioblastoma, the most malignant and most common form of glioma, is known to portend very poor prognosis with the median overall survival of approximately 1.5 years. Its...
Glioblastoma, the most malignant and most common form of glioma, is known to portend very poor prognosis with the median overall survival of approximately 1.5 years. Its treatment requires a multidisciplinary approach, which consists of maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Bevacizumab is approved for newly diagnosed as well as recurrent malignant glioma in Japan. NovoTTF is a novel medical device that emits alternating electric fields; it inhibits the proliferation and growth of the tumor by interfering with tumor cell mitosis at anaphase. A photodynamic therapy with talaporfin sodium has been approved for primary malignant brain tumor including glioblastoma in Japan. For epilepsy secondary to glioblastoma, a novel class of antiepileptics such as levetiracetam and lacosamide is preferred given the lack of drug-drug interactions. Perampanel is a selective antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors; it may be a preferred antiepileptics for glioblastoma, given the and analyses suggesting that it decreases the proliferation and invasion of tumor cells. In this chapter, I describe the overview of the multidisciplinary treatments of glioblastoma. I also describe the future perspectives.
Topics: Brain Neoplasms; Glioblastoma; Humans; Japan; Neoplasm Recurrence, Local; Temozolomide
PubMed: 34092568
DOI: 10.11477/mf.1436204436 -
Journal of Clinical Medicine May 2020A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure...
A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure after chemoradiotherapy (CRT) or radiotherapy (RT). However, only a few studies have reported this therapy in clinical practice. This study aimed to confirm the efficacy and safety of salvage PDT using talaporfin sodium for esophageal cancer in various clinical situations. Twelve patients with esophageal cancer with local failure after definitive CRT or RT who underwent PDT using talaporfin sodium were enrolled from April 2016 to January 2020. Overall, 10 patients (83.3%) achieved a local complete response. No skin phototoxicity was observed, but esophageal stricture occurred in five patients (41.7%). Esophageal stricture was improved with endoscopic balloon dilation in all patients, and subsequent analysis found no significant factors causing esophageal stricture after PDT. Two patients with synchronous tumors were successfully rescued by combination therapy with endoscopic submucosal dissection. Two patients with carcinoma in situ of larger than 1/2 circumference were rescued by repeated PDT. The 2-year overall survival was 80.0% (95% confidence interval 0.409-0.946). PDT using talaporfin sodium was an effective and safe salvage treatment for esophageal cancer with local failure after CRT or RT in various clinical situations.
PubMed: 32429571
DOI: 10.3390/jcm9051509 -
Pharmaceutics Feb 2022Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of...
Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively ( = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively ( = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.
PubMed: 35214085
DOI: 10.3390/pharmaceutics14020353 -
Photodiagnosis and Photodynamic Therapy Jun 2022Photodynamic therapy (PDT) with Talaporfin sodium (Talaporfin) is an effective and safe treatment for central-type early-stage lung cancer (CELC) that is associated with...
BACKGROUNDS/AIM
Photodynamic therapy (PDT) with Talaporfin sodium (Talaporfin) is an effective and safe treatment for central-type early-stage lung cancer (CELC) that is associated with less skin photosensitivity. However, PDT is mostly performed in hospital for the purpose of light shading management in Japan. It is expected that it will be possible to perform PDT with Talaporfin (Talaporfin-PDT) as a day treatment with ≥14 days of shading management at home. This study aimed to confirm the safety of Talaporfin-PDT as day treatment.
METHODS
We retrospectively investigated the occurrence of adverse events among consecutive patients who received PDT for CELC in a day treatment setting in the Respiratory Endoscopy Division of our institution between January 2010 and February 2020.
RESULTS
A total of 12 patients (16 treatments) received day treatment of Talaporfin-PDT. Among the 12 patients, one patient (one treatment) was followed at another hospital. No severe adverse events after treatment were observed among the remaining 11 patients (15 treatments). Mild photosensitivity on a photosensitivity test was observed in 3 (3 treatments) of the 11 patients (15 treatments) but no major photosensitivity was observed. This photosensitivity was a temporary reaction.
CONCLUSION
Talaporfin-PDT for CELC was safely performed as a day treatment.
Topics: Humans; Lung Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retrospective Studies
PubMed: 35367388
DOI: 10.1016/j.pdpdt.2022.102836 -
Yonago Acta Medica Feb 2021Talaporfin sodium photodynamic therapy (TS-PDT) for local failure after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma has recently been...
BACKGROUND
Talaporfin sodium photodynamic therapy (TS-PDT) for local failure after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma has recently been reported to be highly effective and less invasive, compared to other treatment modalities. TS-PDT was recently introduced at the Tottori University Hospital, Japan. The aim of this study is to clarify the efficacy and safety of PDT in our hospital.
METHODS
This was a single-center observational study. We examined eight cases of TS-PDT performed between January 2016 and December 2019. The main endpoints were local complete remission (L-CR) rate and the adverse events. In addition, age, gender, histology, tumor location, TNM stage, tumor depth, irradiation dose, and overall survival (OS) were examined.
RESULTS
The patients included 7 men and a woman, with an average age of 72.1 years (range 63-82 years). The baseline clinical stages before CRT or radiotherapy were stage I in 1, stage II in 3, stage III in 3, and stage IVA in 1 patient. The T stage on endoscopic assessment before TS-PDT was T1 in 6 patients and T2 in 2 patients. Treatment outcomes and adverse events were evaluated. There were no treatment-related deaths, and no significant adverse events occurred intraoperatively or postoperatively. The L-CR rate was 7/8 (87.5%); T1 cases had 100% (6/6) L-CR, while T2 cases had 50% (1/2). The 2-year OS rates were 87%.
CONCLUSION
TS-PDT was observed to be safe and effective in the first eight cases of its application following its introduction in our hospital.
PubMed: 33642911
DOI: 10.33160/yam.2021.02.018