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“New hope for breast cancer patients?”

by Jo Peak | Analysis

18 August 2008

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Drug capsules

Here’s another guest post by Science Information Officer Jo Peak.

Over the last week, there’s been a flurry of headlines concerning a study showing that a particular combination of commonly-used (and cheap) breast cancer drugs can “halt cancer in its tracks”. But do these findings “offer new hope for thousands of breast cancer patients” as the headlines suggest, or is that overstating things? Let’s take a more detailed look at the report….

What did the study show?
The researchers, led by Ingunn Holen and based at the University of Sheffield and Kuopio University in Finland, set out to test whether a drug called zoledronic acid (Zol) could enhance the effects of a standard chemotherapy drug called doxorubicin (Dox) in mice that had been transplanted with early-stage breast cancer cells. Their results are published in the Journal of the National Cancer Institute.

Dox was developed as an anti-cancer drug back in the 1960s and has since been used to treat a variety of different cancer types, including both early and late-stage breast cancer. Zol is a well-established drug used to treat osteoporosis, as it prevents the breakdown of bone. It has also been used as a treatment for people with cancer that has spread to the bone, including breast cancer that has spread.

The researchers tested Dox and Zol on their own, in combination and in different orders. They found that giving Dox to mice with breast cancers, followed 24 hours later by Zol almost completely stopped these tumours from growing. Using the drugs individually or in the reverse order led to far less dramatic effects.

So how significant are these findings?
One of the really positive things to emerge from this study is that Zol appears to enhance the effects of Dox – at least in mice. This suggests that Zol could be used in combination with Dox as an improved treatment for early-stage breast cancer in people.

The media have claimed that this is a “completely new approach to treatment” but this may be overselling the point somewhat. Chemotherapy drugs are often used in ’cocktails’ to achieve better results, and we know from experience that the order in which drugs are given can be a major factor in successful cancer treatment. The benefit of combining Dox with Zol in this way certainly looks promising but, given what we know already, it’s not the ‘completely new approach’ suggested by the articles.

The excitement around this study also partly stems from the fact that both these drugs are already licensed to treat breast cancer. This means that, in contrast to brand new drugs, there are fewer hurdles to overcome in getting these drugs to the patients who could potentially benefit.

In addition, the media have run with the line “cut-price cancer hope” as both these drugs are relatively inexpensive compared with some of the newer breast cancer drugs such as Herceptin. This is timely given NICE’s decision last week not to make four new cancer drugs available on the NHS for the treatment of kidney cancer on the grounds that they are too expensive.

But what are the limitations?

The most important thing to remember is that at the moment, this effect has only been shown in mice. The researchers are now testing this approach in a clinical trial involving 3,000 women with breast cancer. Only once the results of these trials become available will we know if this benefit can be reproduced in humans.

The researchers have shown that the anti-cancer effects of the Dox-Zol combination in mice can be achieved at drug doses lower than those required to see an effect when either drug is used individually. However, the dose of Zol given to the mice was four times higher than that normally given to cancer patients. Whether the same benefits will be achievable with the dose that can safely be given to patients remains to be seen.

It is also important to note that even if these drugs do show added benefit when used in this particular combination in patients, they are far from perfect.

Doxorubicin is what’s known as a cytotoxic drug – it kills cancer cells by damaging their DNA. But it isn’t specifically targeted to cancer cells, and can damage normal tissues, causing side-effects such as fatigue, sickness, hair loss and potential loss of fertility. Occasionally, doxorubicin can cause damage to the heart, so some patients who already have heart problems, such as certain elderly patients, can’t take it.

Zol also has its problems as it is rapidly broken down by the body. Ensuring that enough drug actually gets into the tumour may therefore be a problem.

The ‘take-home’ message

If (and it’s a big ‘IF’) the Dox-Zol drug combination is proven to work in humans as it has done in mice, adopting this approach in the clinic will certainly be a ‘quick win’ for improving the success of breast cancer treatment. However, the limitations of these drugs mean that scientists will certainly not be downing tools and giving up their hunt for other improved breast cancer drugs any time soon.