US health authorities have given the go-ahead to Pafolacianine, a drug that binds to a protein found in large quantities in ovarian cancer cells and allows surgeons to identify them, even when they are invisible.
The FDA (Food and Drug Administration), the body that controls the testing and sale of drugs in the United States, has just given the go-ahead to a molecule called Pafolacianine, which could significantly improve surgery for ovarian cancer, one of the most difficult kinds of cancer to treat.
When the substance is injected intravenously just before surgery and then subjected to light on specific wavelengths, it becomes fluorescent, illuminating the tumour and making extensions and margins that are often not detectable by surgeons with the naked eye, visible. This current technical limitation explains why, in many cases, the tumour is not completely removed and makes it more likely to recur.
Alex Gorovets, director of the FDA's Center for Drug Evaluation and Research, confirms: "The green light for Pafolacianine may help improve surgeons' ability to remove dangerous ovarian tumours that might otherwise go undetected.”
So how does it work? The outer walls of ovarian cancer cells almost always have large amounts of proteins called folate receptors (folates are part of the vitamin B group). Pafolacianine administered intravenously binds to these proteins and becomes visible when lit with a special near-infrared fluorescence system (to give it its technical name). At the moment surgeons rely on classic pre-operative 'imaging' tests (CT scans, MRIs and others), visual observation of tumours under normal lighting conditions during surgery, and even tactile examination to identify cancerous lesions.
A study of 150 women
Pafolacianine was authorised by US authorities after a number of clinical trials to test the new molecule. The most important of these, phase 3 (the stage closest to possible commercialisation), was conducted by doctors at the University of Pennsylvania, in partnership with its specialist manufacturer, One Target.
As reported in the Journal of Clinical Oncology, in this study 150 women with ovarian cancer due to undergo surgery at 11 centres in the USA and the Netherlands were given Cytalux (the drug's commercial name) and then assessed under standard conditions, or after illumination with fluorescent light.
In approximately one in three cases, a mass was found that could not be seen or felt by surgical palpation, in areas of the abdomen where no surgery was planned. There were, however, cases of false positives (in 32% of lesions removed using Cytalux, which is a high percentage), but the new technique has proved decisive and the right one for operations on more advanced tumours – those with increased risk. In these cases, sensitivity (the ability to find what was being sought) was 83%. This meant that a radical operation – one in which the whole tumoral mass was removed (at least in theory) – was possible in 62% of patients.
Pafolacianine was obtained after more than ten years' research, which involved testing a range of possible compounds on over 1,200 women.
A difficult tumour to diagnose
Unfortunately, only in one of five cases of ovarian tumours are diagnosed in time, when they are still at an early stage and can be treated more effectively. This is because there are no markers that can detect them in advance and symptoms are not very specific. As a result, by the time the tumour is diagnosed and surgery is carried out, the disease may have already spread to other organs in the abdomen. But cancer cell clusters that have 'migrated' become difficult to detect, so tumour-specific illumination could make a huge difference.
Researchers are already looking at trialling similar fluorescent markers for other types of cancer that are especially difficult to treat, such as some forms of carcinomas of the head and neck, brain, lung, and genitourinary tract.