New method of treatment for ovarian cancer

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A new way of treating ovarian cancer could reduce the serious side-effects of chemotherapy and increase the amount of cancer-fighting drugs doctors can safely administer to their patients.

A scientific team led by professors Dr. Christine Allen, a chemist, and Dr. Micheline Piquette-Miller, a biologist, has developed a system to bring drugs directly to the ovaries at their University of Toronto laboratory. Although Drs. Allen and Piquette-Miller developed the treatment for ovarian cancer, it could also be used to fight other types of cancer.

The project, which is funded by the Ontario Institute for Cancer Research, is in the last stage of research before it can be tested in a clinical trial.

Typically, ovarian cancer treatment is a two-step process: surgeons first remove as much of the tumour as possible, then oncologists administer chemotherapy, a drug containing a chemical called paclitaxel. This drug is injected intravenously and reaches the cancer cells through the bloodstream.

While paclitaxel is effective in destroying cancer cells, other ingredients need to be added if the therapy is administered intravenously. One of these ingredients, cremophor EL, can be toxic.

To this end, they designed an implant that slowly releases the drug over two months. “It does require surgery, but it isn’t as invasive as it sounds – the idea is that it would be implanted right after surgeons remove most of the tumour,” Dr. Allen says.

Because it will be inside a patient, the implant – a thin, one square centimetre film-like substance – has to hold the paclitaxel over a period of time and release it at a slow and steady rate. It also has to be biocompatible, meaning that it isn’t toxic, and biodegradable, so it breaks down naturally and doesn’t have to be surgically removed after treatment.

After creating several types of hydrogels (film-like substances) the researchers found a formula that is capable of holding the drug. Before the paclitaxel is fused with the hydrogel, it is loaded into microscopic bits of matter called nanoparticles, which are smaller than one 10 millionth of a metre.

Further testing showed that the hydrogel is doing exactly what it is supposed to: steadily releasing paclitaxel over a period of months.

Even more important, they also found that when the drug is released, it is very effective at killing cancer cells. One version of the implant containing a high concentration of paclitaxel killed over 90 per cent of cancer cells in a laboratory experiment.

The high-concentration doses that make the treatment so effective are only possible because of the implant system. “We found that the implant system increases the maximum safe dose of paclitaxel that can be given to a patient,” says Dr. Allen.

Aside from receiving more paclitaxel with fewer side effects, the implant could benefit patients another way: after their surgery, they will no longer have to frequently return to the hospital for time-consuming and often stressful chemotherapy sessions.

The researchers have also developed a gel-based form of paclitaxel, which can be injected near the ovaries. This would make it possible to deliver the non-toxic, higher-dose formula at any time, not just after surgery.

Once they realized the potential of their approach, Drs. Allen and Piquette-Miller patented their innovation. They are now in discussion with pharmaceutical companies about turning their invention into a treatment that will eventually be used in hospitals. Commercial drug developers are also considering the implant to treat other cancers.

Although research has shown the new treatment is effective, one final study is needed. Once that is complete, the next step is a clinical trial, which could take several years and involve patients at multiple hospitals.

But given the potential benefit to patients, Dr. Allen believes years of research and studies are worth the effort.

“So far we haven’t found any disadvantages to direct delivery through an implant, but we know there are many advantages.”

The National Cancer Institute, a prominent research organization in the United States, agrees. It has recently recommended that scientists should explore ways to deliver treatments in the abdominal area, rather than only intravenously.

Dr. Allen says that, “hopefully, this will mean our research has a greater impact than we’d originally imagined.”