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Ovarian cancer treatment – a bright future

Posted Mar 14 2011 12:00am

Survival rates for ovarian cancer have almost doubled over the last thirty years, as we pointed out in our press release last week.

Our statisticians have looked at data on ovarian cancer rates around the country and estimated that in England and Wales, 1,000 more women are now surviving the disease every year, compared with the early 70s.

But with all silver linings, there’s often a cloud nearby – survival rates for women with more advanced disease haven’t improved by nearly as much as it has for those whose disease is caught early. And unfortunately ovarian cancer is usually diagnosed late, when it’s spread. So there’s still the potential to save even more lives by detecting the disease earlier.

The new statistics also highlight the urgent need for better treatments for those women who are diagnosed at a later stage. And crucially, we need to find a way to treat women whose cancers have become resistant to their initial therapy.

So how can we improve this situation? And what’s on the horizon in terms of new treatments?

Before we look to the future, it’s worth putting things in context.

Ovarian cancer is currently the 5th most common cancer in UK women. According to the latest figures, more than 6,500 women are diagnosed with the disease every year, and around 4,400 die. This latter figure works out as 9.7 ovarian cancer deaths per 100,000 women in the UK.

Another feature of ovarian cancer (as with many cancers), is that survival rates for the disease vary greatly according to how early the disease is diagnosed. (As we’ve discussed before, cancer survival rates are often measured in terms of ‘five-year survival’ – the proportion of women still alive five years after being diagnosed.)

For example, according to data from the Anglia Cancer Network, if you follow 100 women diagnosed with the earliest stage of ovarian cancer for five years, on average more than 90 will have survived their disease. But if you take 100 women diagnosed with the most advanced stage of ovarian cancer, when it has spread to distant parts of the body, only five or six will have done so.

The following graph shows how survival for different stages of the disease has changed since 1987:

As you can see, most of the overall change is due to the large increase in survival among women diagnosed with stage II disease.

But only about a third of women are diagnosed with ‘stage II’ disease or earlier. (There’s information about the different stages of ovarian cancer on CancerHelp UK)

There are several possible reasons why we’re seeing the increase in survival, but two stand out.

Firstly, chemotherapy for the disease has improved – in particular, there’s now widespread access to a drug called carboplatin , which Cancer Research UK scientists developed . Carboplatin offered doctors not just a better treatment for women initially diagnosed with the disease, but a better way to manage the disease if it came back.

But the improvement’s also linked to the introduction of specialised gynaecological surgeons , who regularly operate on diseases like ovarian cancer, and who tend to have a better success rate than general surgeons.

As well as these improvements in treatment, there’s also the possibility that at least some of the change is due to improvements in the way the disease is classified. In particular, it’s possible that better surgeons have collected better quality staging data – and ovarian cancers that might have been mistakenly classified as ‘early’ are now properly classified as later stage disease.

Whatever the reasons for the changes, there’s still a lot to learn about the disease. For instance, it’s now becoming apparent that what we call ‘ovarian cancer’ is in fact at least three distinct – and very different – diseases.

The main type is known as ‘high-grade serous’ ovarian cancer, and this makes up the majority of cases. Evidence is now emerging that these cancers may not even start in the ovaries, but instead originate in the cells that make up the fallopian tubes .

It now seems that these cancers are driven by a very distinct set of defective genes – including, in about a quarter of cases , a pair of genes known as BRCA1 and BRCA2, which are infamous for their role in inherited breast cancers.

(Two other types of ovarian cancer – endometrioid and clear cell – account for about two out of every 10 cancers, and are less strongly linked to mutations in BRCA genes. The remainder of cases are made up of a fourth form, called mucinous cancer, and others that are impossible to classify).

As regular readers of this blog will know, new types of cancer drug, collectively called PARP inhibitors are  generating a lot of excitement in the research community. PARP inhibitors have been carefully designed to treat cancers driven by faulty BRCA genes, and Cancer Research UK scientists have been instrumental in their development.

Most of the trials carried out so far have looked at whether PARP inhibitors can treat women with breast cancer caused by inherited BRCA gene faults, who make up about five per cent of breast cancer cases. Finding that faulty BRCA 1 and 2 genes are common in serous ovarian cancer is exciting, and means that that these drugs may ultimately be useful for women with this form of the disease.

According to Cancer Research UK’s ovarian cancer expert Dr James Brenton , one intriguing possibility is that these women could first be given a platinum drug for a short period, and then longer term PARP inhibitor treatment to ‘mop up’ any remaining cancer cells. As PARP inhibitors can be taken as tablets (rather than intravenously), this would be especially convenient as an outpatient treatment.

This is a strategy that a team of researchers led by Professor Jonathan Lederman at UCL has been testing  in a clinical trial . Results are expected this summer.

Dr Brenton is planning to test a similar approach in the near future. He told us he’s extremely optimistic that PARP inhibitors will play a wider role in high grade serous ovarian cancer in the future, potentially curing even more women than we do today:

“Ovarian cancer is starting to become a more controllable chronic disease but a cure remains elusive in most cases,” he said.

“We need to investigate the full potential of targeted treatments such as PARP inhibitors in ovarian cancer, as women with the high-grade serous type may have undiagnosed faults in BRCA1 and BRCA2, or other alterations in their cancer, which makes them very sensitive to this drug,” he told us.

His sentiments echo remarks made at last year’s NCRI cancer conference, when Professor Stan Kaye from the Institute of Cancer Research gave an excellent talk about the future of ovarian cancer treatment ( which you can read here )

But along with trying to improve treatments, diagnosing ovarian cancer earlier will also save lives.

We’re supporting several efforts to do this: the huge UKCTOCS screening trial we wrote about in 2009 is continuing to gather data and researchers worldwide are investigating new ways to detect and monitor the disease.

To this end, we’ve just awarded Professor Ian Jacobs , one of the leading UK experts in ovarian cancer detection, a five-year programme grant to investigate new molecular tests (biomarkers)  for early ovarian cancer.

So it’s not just the statistics that are giving us cause for optimism. Research going on right now, in labs around the UK, could lead to even greater improvements in our understanding of ovarian cancer – both how to treat it, and how to detect it earlier.

And at some point in the not-too-distant future, we hope the fruits of this research will mean that the outlook for women diagnosed with ovarian cancer, at any stage, will be a good deal brighter than it is now.

Henry

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