Current Approaches in Bladder Cancer Treatment Jan 2025 :-) Photodynamic Therapy
Photodynamic therapy is a unique technique to kill cancer cells using a specific wavelength of light and a suitable photosensitizer. Photosensitizers are administered systemically or in a site-specific manner, intravesically, intratumorally, topically or intraperitoneally. Once illuminated with a specific wavelength laser, a nontoxic photosensitizer is activated and transfers electrons to molecular oxygen, an electron acceptor, converting it into singlet oxygen. The singlet oxygen (SO) can have a cytotoxic effect on tumors or their associated vessels by causing necrosis or apoptosis.
(113) The FDA has approved PDT for the treatment of esophageal, skin, and non small cell lung cancer, and multiple clinical trials are currently being performed for bladder cancer.
(114,115) Rassmussan-Taxdal and colleagues performed the first successful photodetection studies in 1955, treating cancer patients with hematoporphyrin hydrochloride and identifying tumor cells during histological examinations.
(116) The first PDT clinical trial was reported in 1978, using intravenous hematoporphyrin derivatives (HPD) combined with local red-light exposure.
(117) A CR or PR was observed in 99% of the cutaneous or malignant lesions treated. In this trial, no bladder cancer patients were enrolled. Benson et al. reported that three of four patients treated with HPD in 1983 who had recurrent transitional cell carcinomas (TCCs) and were failing chemotherapy remained cancer-free
(118) In 1983 Thomas Dougherty discovered that crude hematoporphyrin contains a variety of porphyrins, which led to the development of photofrin.
(119) Porphyrins such as protoporphyrin and hydroxyethyl vinyl deuteroporphyrin are produced when these are converted to HPD by acetylation. A year later, Dougherty et al.
(120) proposed that HPD is made up of two porphyrin units linked by an ether bond. This compound is called dihematoporphyrin ether (DHE). In summary, photofrin is a mix of monomers, dimers, and oligomers that all contain the porphyrin moiety. Photofrin was the first versatile photosensitizer to gain FDA approval, and it remains the most popular photosensitizer today. In 1993, the Canadian government approved the use of photofrin-PDT to treat bladder cancer.
(114) These agents produce fluorescence upon light illumination and in addition to the photodynamic effect, can be used for tumor detection. Hemotoporphyrins, porphyrins, HPDs, and aminolevulinic acid (ALA) derivatives are being investigated for tumor detection. In an ongoing
Phase II clinical PDT trial (NCT03945162) (121) patients with or without papillary carcinoma in situ (CIS), that are unresponsive to BCG are given a single instillation of Ruvidar (TLD-1433) at a therapeutic dose of 0.7 mg/cm
2 is administered intravesically into the bladder for approximately 60 min followed by laser activation at 520 nm under general anesthesia, delivering a total of 90 J/cm
2 of laser light after rinsing Ruvidar from the bladder. Two study treatments will be conducted: a primary treatment on Day 0 and a maintenance treatment on Day 180.
According to the interim data, PDT provides an acceptable ongoing safetyprofile for patients with BCG unresponsive CIS (± papillary disease). (121)
A Comprehensive Review of Current Approaches in Bladder Cancer Treatment | ACS Pharmacology & Translational Science