Wednesday August 13 2008
The combination is currently being tested in women with breast cancer
A drug used to “treat brittle bones helps halt breast cancer”, the Daily Mail reports. When combined with chemotherapy medication, the drug zoledronic acid, normally used in the treatment of osteoporosis, almost stopped tumour growth in mice and “the cancer remained at bay even after the treatment had finished”, the newspaper says. There are hopes that the drug will have the same effect in humans and further trials have begun.
However, it is not certain how this mouse model relates to humans. Additionally, both zoledronic acid and the chemotherapy drug doxorubicin were given in much higher doses and for a longer duration than would be given in humans. This drug combination, however, has demonstrated that it may have potential in preventing the growth of early stage cancer that has not spread outside of the breast. Research will continue but it will have no direct implication upon the treatment of breast cancer in the immediate future.
Where did the story come from?
Doctor Penelope Ottewell and colleagues from the Department of Biomedical Sciences, University of Sheffield, and the Department of Pharmaceutics, University of Kuopio, Finland, carried out this research. The study was funded by Breast Cancer Campaign UK, Medical Research Council, Academy of Finland, Finnish Cultural Foundation and Saastamoinen Foundation. It was published in the peer-reviewed Journal of the National Cancer Institute.
What kind of scientific study was this?
This was a laboratory study in mice. Zoledronic acid is a drug that prevents the minerals in the bone from being broken down (bone resorption), therefore protecting against brittle bones. It has previously been demonstrated to enhance the antitumour effects of chemotherapy drugs in the laboratory, and also found to be effective in live animal models (investigating a variety of cancers and tumour-induced bone damage).
In this study, human breast cancer cells (obtained from cell cultures grown in the laboratory) were “infected” with DNA that produces a green fluorescent protein, to allow these cells to be easily identified during the experiment. The cells were then injected beneath the skin of 130 six-week-old female mice. Mice that had developed palpable tumours (that is, tumours that could be felt under the skin) were then randomly assigned to six weeks of treatment in one of three groups: once weekly doxorubicin injections at different concentrations; once weekly zoledronic acid injections at different concentrations; or once weekly combination treatment (both drugs injected at the same time, or either drug followed 24 hours later by the other). For comparison, they also included mice injected with only salt solution (controls). After six weeks the tumours were cut out for analysis of tumour volume, tumour proliferation and tumour cell death. They also examined leg bones from each mouse.
What were the results of the study?
A total of 108 (83%) of mice that had been injected with tumour cells developed a palpable tumour within one week. The mice that were injected with either zoledronic acid or doxorubicin alone, or zoledronic acid followed 24 hours later by doxorubicin, had tumours of similar volume to those mice injected with only salt solution (control mice).
The mice injected with zoledronic acid and doxorubicin at the same time had significantly smaller tumour volumes compared with the mice injected with either drug alone or those injected with zoledronic acid followed 24 hours later by doxorubicin.
However, injection of doxorubicin followed 24 hours later by zoledronic acid gave the greatest reduction in tumour volume. Compared with all other treatments, doxorubicin followed by zoledronic acid significantly increased the number of tumour cells undergoing cell death and significantly decreased the number of tumour cells proliferating (dividing to make more tumour cells). Analysis of the leg bones did not demonstrate any spread of disease to the bones in all groups.
What interpretations did the researchers draw from these results?
The researchers concluded that doxorubicin followed by zoledronic acid can give substantial antitumour effects in an animal model representative of subcutaneous breast cancer without bone involvement.
What does the NHS Knowledge Service make of this study?
This study delivers promising results which will promote further research into whether combining zoledronic acid with doxorubicin chemotherapy can be beneficial for people with early stage breast cancer that has not spread outside of the breast. However, it is important to note that the current trial has been conducted only in mice and it is not certain how the mouse model relates to humans. Additionally, both zoledronic acid and the chemotherapy drug doxorubicin were given in much higher doses and for a longer duration than would be given in humans. Although doxorubicin is widely used to treat breast cancer, bisphosphonates such as zoledronic acid are normally used only in people with advanced breast cancer who have disease that has spread to the bone. Research into this treatment combination is ongoing but it will have no direct implication upon the treatment of breast cancer in the immediate future.
Sir Muir Gray adds...
Let's see what the human studies say.