新型光敏剂Tookad(padeliprofin)由STEBA Biotech公司开发,于2017年11月10日获CHMP推荐批准该药作为局灶性血管靶向光动力疗法(VTP),用于前列腺腺癌成人患者的治疗。
该药的活性药物成分padeliprofin是一种用于光动力/放射治疗的增敏剂,当被激光激活时,能触发一系列的病理生理事件,数日内便可造成局灶性坏死。
临床数据显示;与主动监测(对已知的前列腺癌定期监测)相比,Tookad能提高第24个月时活检阴性的可能性以及延迟病情进展。Tookad申请的适应症为:作为一种单药疗法,用于既往未接受治疗(初治)、预期寿命≥10年、单侧、低风险前列腺腺癌成人患者。
Photodynamic therapy is a minimally invasive way to destroy a cancer tumor in the body without surgery or radiation. There are three components to this treatment:
The intravenous (IV, or in a vein) injection of a special drug called a photosensitizer. This drug travels throughout the bloodstream, including the area containing the tumor.
During the treatment, activating the photosensitizer by applying a light at a near-infrared wavelength carried by a fiber optic tube into the tumor. The light can penetrate a very small distance into tissue and activates the drug that is present in the blood vessels at that location.
When the light source “excites” the drug in the tumor’s blood vessels, it causes the release of a type of oxygen that is toxic to cancer cells. For prostate tumors, this can cause the cancer cells to die off, and the blood vessels that feed the tumor become blocked (occluded) which further contributes to the death of the cancer cells.
Different types of photosensitizers exist for different types of cancer, including some skin and organ cancers.
Once in the body, they don’t do anything until exposed to the light source; however, in the early days of photodynamic therapy, the drugs were administered as much as 2 days in advance of the treatment, and patients were advised to avoid sunlight as the drugs could cause skin damage.
For treating prostate cancer, the photosynthesizer TOOKAD® soluble (WST11) is used. The technical term for this treatment is TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy, and it has been clinically tested as a focal therapy for low-risk (Gleason 3+3) tumors in which the side of the gland containing the tumor was ablated (hemiablation).
The procedure is done under anesthesia, and takes about 2 hours from start to finish. During the procedure, TOOKAD is given as a 10-minute IV infusion, after which the optic fibers are inserted into the prostate through the perineum under ultrasound guidance.
The light source is then applied to the tumor for 20-25 minutes.
As a precaution against eye photosensitivity, patients wear protective eyewear and stay in low level light for an hour after the treatment, and a urinary catheter is left in place for 24 hours.
Although there is no long term effectiveness data on TOOKAD VTP, a recent multicenter study reported findings similar to other earlier studies, suggesting that the procedure is “well tolerated and resulted in a negative biopsy in the treated lobe in majority of menThe photosensitizing drug TOOKAD has been shown to have fewer side effects than previous generations of such agents; it is more soluble in water and is believed to quickly wash out of the body.
However, caution is always required in the use of any intravenous pharmaceutical, especially one that is activated in the presence of light.
In the Azzouzi et al. (2013) study, two patients had “serious” adverse events related to TOOKAD:
One manhad ischaemic optic neuropathy [a stroke of the optic nerve resulting in vision loss] that resolved with a small defect in the visual field and was considered possibly related to study drug by the investigator but not by the sponsor. One man had an inflammatory prostatic cyst 193 days after the VTP… which was considered related to study drug and device by both the investigator and the sponsor.[iii]
TOOKAD VTP as a focal treatment for prostate cancer has the potential to destroy the tumor with very minimal risk to urinary and sexual function. Until it is approved in the U.S., interested patients must travel to Mexico or Europe for the treatment. However, whether now or in the future, patients interested in a focal treatment but uncomfortable with the idea of a photosensitizing agent in their bloodstream may want to consider focal laser ablation (FLA). MRI-guided FLA also uses light, but in this case it is the direct application of a laser beam into the tumor, which creates extreme heat to destroy the tumor and its blood vessels in less than 2 minutes. FLA requires no surgery, no radiation, and no photosensitizers circulating in the body—and it is FDA-cleared for use in the U.S.