Cheap drug hope for breast cancer
A combination of two inexpensive existing drugs may offer a new way to treat breast cancer, according to UK and Finnish researchers.
The common chemotherapy drug and a brittle bone medicine almost completely stopped the growth of tumours in mice.
The Journal of the National Cancer Institute said the combination cost a twentieth of Herceptin, given to breast cancer patients by the NHS.
Specialists said the results of human trials now under way would be crucial.
| The results of this study could change the way breast cancer patients are treated
Pamela Goldberg
Breast Cancer Campaign |
In the UK, almost 46,000 new cases of breast cancer are diagnosed each year.
Although modern treatments mean that cases caught sufficiently early, some via breast screening programmes, have an excellent chance of being successfully treated.
The study was a joint project between researchers at the University of Sheffield and the Kuopio University in Finland.
Its findings could offer an even more effective way to help some patients.
It used a dose of the drug doxorubicin, a common component of chemotherapy regimes, followed 24 hours later by zoledronic acid, currently given to osteoporosis patients.
In the mice, this stopped 99.99% of new cancer cell growth in tumours.
It is thought the first drug could be "priming" the tumour to be more sensitive to the cancer-cell killing qualities of the second drug.
Dr Ingunn Holen, who led the study, said that the study showed that the drug cocktail could "kill breast tumours".
"These results show that a patient may benefit the most if these two drugs are given in this particular order."
She said that the results of a human trial were expected later this year.
Speed advantage
If that proves successful, the drugs would not have to undergo a lengthy licensing process, simply have the change of use included in their current licence.
Breast Cancer Campaign, the charity which funded the study, said it was encouraged by the potential for the drug to be made swiftly available to women.
Its chief executive, Pamela Goldberg, said: "The results of this study could change the way breast cancer patients are treated.
"The good news is the that the two treatments are relatively inexpensive and already used in the clinic."
A spokesman for Cancer Research UK said that a study in humans would be important.
"Establishing the most effective combinations of drug treatments and the timings in which they are given is an important area of clinical research.
"But the benefits of giving zoledronic acid after doxorubicin have only been shown here in mice and now need to be evaluated more fully in people with breast cancer."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/h...th/7558327.stm
Published: 2008/08/13 10:25:34 GMT
© BBC MMVIII
And the pubmed abstract:
- J Natl Cancer Inst. 2008 Aug 20;100(16):1167-78. Epub 2008 Aug 11.
Links
- Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer.
Ottewell PD, Mönkkönen H, Jones M, Lefley DV, Coleman RE, Holen I.
Academic Unit of Clinical Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. i.holen@sheffield.ac.uk.
BACKGROUND: The potent antiresorptive drug zoledronic acid (Zol) enhances the antitumor effects of chemotherapy agents in vitro. We investigated the effects of clinically achievable doses of doxorubicin (Dox) and Zol, given alone, in sequence, and in combination, on the growth of established breast tumors in vivo. METHODS: Female MF1 nude mice were inoculated subcutaneously with 5 x 10(5) human breast cancer MDA-MB-436 cells that stably expressed green fluorescent protein (ie, MDA-G8 cells). Beginning on day 7 after tumor cell injection, the mice were injected weekly for 6 weeks with saline, Dox (2 mg/kg body weight via intravenous injection), Zol (100 microg/kg body weight via intraperitoneal injection), Dox plus Zol, Zol followed 24 hours later by Dox, or Dox followed 24 hours later by Zol (n = 8-9 mice per group). The effects of treatment on tumor growth were determined by measuring tumor volume; on tumor cell apoptosis and proliferation by immunohistochemistry using antibodies for caspase-3 and Ki-67, respectively; and on bone by microcomputed tomography and bone histomorphometry. All P values are two-sided. RESULTS: Treatment with Dox or Zol alone or Zol followed 24 hours later by Dox did not statistically significantly decrease final tumor volume compared with saline. Mice treated with Dox plus Zol had statistically significantly smaller final tumor volumes than those treated with Dox alone (mean = 122 mm(3) vs 328 mm(3), difference = 206 mm(3), 95% confidence interval [CI] = 78 to 335 mm(3), P < .001), with Zol alone (122 mm(3) vs 447 mm(3), difference = 325 mm(3), 95% CI = 197 to 454 mm(3), P < .001), or with Zol followed 24 hours later by Dox (122 mm(3) vs 418 mm(3), difference = 296 mm(3), 95% CI = 168 to 426 mm(3), P < .001). Treatment with Dox followed 24 hours later by Zol almost completely abolished tumor growth. Tumors from mice that were treated with Dox followed by Zol had more caspase-3-positive cells than tumors from mice treated with saline (mean number of caspase-3-positive cells per square millimeter: 605.0 vs 82.19, difference = 522.8, 95% CI = 488.2 to 557.4, P < .001), with Zol alone (605.0 vs 98.44, difference = 506.6, 95% CI = 472.0 to 541.2, P < .001), or with Zol followed by Dox (605.0 vs 103.1, difference = 501.9, 95% CI = 467.3 to 536.5, P < .001). The treatment-induced increase in the number of caspase-3-positive cells was mirrored by a decrease in the number of tumor cells positive for the proliferation marker Ki-67. No evidence of bone disease was detected in any of the treatment groups following microcomputed tomography and histological analysis of bone. CONCLUSION: Sequential treatment with Dox followed by Zol elicited substantial antitumor effects in subcutaneous breast tumors in vivo, in the absence of bone disease.
http://jnci.oxfordjournals.org/cgi/c...ct/100/16/1167
Results: Treatment with Dox or Zol alone or Zol followed 24 hours later
by Dox did not statistically significantly decrease final tumor
volume compared with saline. Mice treated with Dox plus Zol
had statistically significantly smaller final tumor volumes
than those treated with Dox alone (mean = 122 mm
3 vs 328 mm
3,
difference = 206 mm
3, 95% confidence interval [CI] = 78 to 335
mm
3,
P < .001), with Zol alone (122 mm
3 vs 447 mm
3, difference
= 325 mm
3, 95% CI = 197 to 454 mm
3,
P < .001), or with Zol
followed 24 hours later by Dox (122 mm
3 vs 418 mm
3, difference
= 296 mm
3, 95% CI = 168 to 426 mm
3,
P < .001). Treatment
with Dox followed 24 hours later by Zol almost completely abolished
tumor growth. Tumors from mice that were treated with Dox followed
by Zol had more caspase-3–positive cells than tumors from
mice treated with saline (mean number of caspase-3–positive
cells per square millimeter: 605.0 vs 82.19, difference = 522.8,
95% CI = 488.2 to 557.4,
P < .001), with Zol alone (605.0
vs 98.44, difference = 506.6, 95% CI = 472.0 to 541.2,
P <
.001), or with Zol followed by Dox (605.0 vs 103.1, difference
= 501.9, 95% CI = 467.3 to 536.5,
P < .001). The treatment-induced
increase in the number of caspase-3–positive cells was
mirrored by a decrease in the number of tumor cells positive
for the proliferation marker Ki-67. No evidence of bone disease
was detected in any of the treatment groups following microcomputed
tomography and histological analysis of bone.
Conclusion: Sequential treatment with Dox followed by Zol elicited substantial
antitumor effects in subcutaneous breast tumors in vivo, in
the absence of bone disease.
CONTEXT AND CAVEATS Prior knowledge
Zoledronic acid is a potent inhibitor of osteoclastic bone resorption that also enhances the antitumor effects of chemotherapy agents both in vitro and in in vivo models with a high degree of tumor-induced bone disease.
Study design
An examination of the effects of clinically achievable doses of doxorubicin and zoledronic acid, given alone, in sequence, and in combination, on the growth of tumors derived from a human breast cell line that does not metastasize readily to bone in a mouse model.
Contribution
Sequential treatment with doxorubicin followed by zoledronic acid inhibited the growth of subcutaneous breast tumors in vivo, in the absence of bone disease.
Implications
There may be benefits of combining zoledronic acid with cytotoxic agents for the treatment of patients with early-stage breast cancer.
Limitations
Mice were treated with higher total doses of the drugs than those that breast cancer patients receive. The relevance of the mouse model to humans is not certain.
From the Editors
|
Manuscript received December 17, 2008; revised June 2, 2008; accepted June 16, 2008.
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