This Breast Cancer Drugs review was first published in 2004. As such it could be described as a little out of date. We have left it up on site because we felt that any woman (or man) about to use breast cancer drugs from Tamoxifen to Herceptin or arimidex, (breast cancer chemotherapy) will appreciate the details in this cancer drugs review.
You can read the very latest review on any chemotherapy drug by clicking here.
Breast Cancer Drugs
Compiled by Melanie Hart
Youve been diagnosed with cancer and your oncologist explains which course of treatment he recommends, and which drugs he will be administering.
While you may have heard or read about some of them, there are clinical trials underway here and in the States on several new ones - and on new uses for existing drugs.
Yes, it can be very confusing, so read on to find out the uses, proven benefits and risks of the main breast cancer drugs used in the UK today, with expert opinion from Professor Trevor Powles who started the first tamoxifen prevention trials during his 32 years at The Royal Marsden.
Chemotherapy drugs
Adriamycin (doxorubicin) made by Pharmacia
Adriamycin is used to treat breast and other cancers. It is toxic to cancer cells, arid is administered intravenously.
Side effects may include: decreased white blood cell and platelet counts, increased risk of infection, Loss of appetite, darkening of nail beds and skin creases of hands, hair loss, nausea and vomiting, mouth sores and, at higher doses, it may be toxic to the heart.
Patients with pre-existinq heart problems may need to have a cardiac evaluation before use.
"This drug is more commonly used in the States," says Professor Trevor Powles. "Its proven benefits are that it reduces the risk of relapse and prolongs survival in patients, with operable breast cancer, when used in a drug combination. The long-term risks are very little with the dose that we use.
Epirubicin (pharmorubicin) made by Pharmacia
Epirubicin has similar activity to adriamycin and has been approved for use worldwide since the 1990s. Clinical trials have shown that combinations of chemotherapy are more active and increase a woman chance of surviving breast cancer if they include epirubicin or adriamycin. It is given intravenously in combination with two other chemotherapy drugs, cyclophosphaniide and fluorouracil.
Side effects are similar to adriamycin, but it is less toxic on the head. Prof. Powles, "This is quite an important drug because its the one most widely used in Europe. Its a later model than Adriamycin and has slightly less cardiotoxicity."
Cyclophosphamide (cytoxan) made by Asta Medica
Like adriamycin, cyclophosphamide is toxic to cancer cells. It is taken orally, in tablet form, or intravenously over 30-60 minutes.
Side effects may include decreased white blood cell count with increased risk of infection, hair loss, nausea and vomiting, loss of appetite, mouth or lip sores, diarrhoea, no menstruation.
Mitozantrone (Novantrone) made by Lederle Laboratories
This works similarly to adriamycin, but has much less cardiotoxicity.
Side effects may include: as above, but less hair loss and nausea, also mouth or lip sores, stomach pain, shortness of breath and it may stop periods.
Prof. Powles. "This drug is generally better tolerated than the others. I tend to use this rather than adriamycin in frailer patients
Xeloda (capecitabine) made by Roche Laboratories
Xeloda can be taken orally and operates by targeting tumour cells - leaving healthy cells relatively unharmed. Each tablet contains a toxic agent fluorouracil which is activated only when it reaches the site of the tumour, by an enzyme found at high levels in cancer cells and low levels in normal ones. Xeloda has been FDA approved since April 1998 in the US as a treatment for advanced breast cancer in patients who have not responded well to chemotherapy that included taxol and an antbracycline (such as adriamycin). Trials have shown that it can prolong the lives of women whose cancer has spread to other organs. In some patients, xeloda helped shrink tumour size by killing cancer cells.
Side effects may include diarrhoea, nausea and vomiting, mouth and throat sores, decreased appetite, skin rash, dehydration. Some of the side effects from xeloda may become severe.
Prof. Powles: "This is a very important drug, and trials show it produces results used with a taxane and on its own. It seems to be a better modulator than other chemotherapy drugs. Xeloda is licensed for use with taxotere, in advanced breast cancer, and is in trials for use in patients with operable breast cancer."
Trials are also underway on another chemotherapy drug, gemcitabine (Gemzar) which is not licensed for use with breast cancer, It is used widely in the US for lung and pancreatic cancer Vinorelbine (Navelbine) is also in trials and used in the US.
Prof. Powles says, "We used to use vincristine a lot, but that had a marked neurotoxicity (it caused a lot of problems with peripheral nerves), vinorelbine has a better toxicity profile."
Chemotherapy combinations
Professor Powles says the most common chemotherapy combinations used to treat operable breast cancer in the UK are:
By using drugs in combination youre picking up the benefits of three drugs versus one
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FEC - flurouracil. epirubicin and clyclophosphamide
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AC - adriamycin and clyclophosphanuide
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FAC - using adriamycin instead of epirubicin
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CMF - clyclophosphamide. methotrexate and fluoric
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MM - mitozantrone and methotrexate
"I personally use FEC or AC, because tberes a lot of data on both of those and theres nothing to choose between them in benefits and risks he explains." FAC is similar, but has Less data. These combinations have been evaluated in trials involving 10,000 women with operable breast cancer. With up to 15 years follow up, there is a significant reduction in the risk of breast cancer relapse and death - and no increase in non-cancer deaths. Trials have been done to show these combinations are more effective than CMF. MM is probably as effective, but no ones done the trial to show that. I use MM or CMF if someone has a heart problem, or is frail. If they are too frail I might not give adjuvant therapy at all.
"By using drugs in combination youre picking up the benefits of three drugs versus one. You can drop the dose to have less side effects and make sure that toxicities dont cross over with each other"
The Taxanes
Taxol (paclitaxel) made by Bristol-Myers Squibb
Taxol was first taken from a Pacific yew tree. It was approved by the FDA in 1992 to treat advanced (metastatic) breast cancer. In 1999, the FDA also approved Taxol, in the US, to treat early breast cancer in patients who have already received chemotherapy with the drug, adriamycin. It is still in trials for that use here. Taxol is called a mitotic inhibitor because it interferes with cells during mitosis (cell division). It is usually given intravenously. Side effects may include: a reduced white blood cell count hair loss, numbness and or tingling in hands or feet painful muscles and joints. On rare occasions It can slow the heart rate and may temporarily affect the liver.
Taxotere inhibits the division of breast cancer cells by acting on the cells internal skeleton
Taxotere (docetaxel) made by Aventis
Taxotere resembles taxol in chemical structure. Taxotere was FDA approved in 1996 to treat advanced breast cancer in patients who have not responded well to chemotherapy with adriamycin. In 1998, taxotere was also approved by the FDA to treat cancer that has spread into other areas of the breast or other parts of the body after treatment with standard chemotherapy. Taxotere inhibits the division of breast cancer cells by acting on the cells internal skeleton. The drug is usually given intravenously once every three weeks. Because the side effects can be bothersome, additional drugs can be prescribed to help counter them. For example, dexamethasone is commonly used to prevent fluid retention while on taxotere.
Possible side effects include: decrease in white blood cells, fever (often a warning sign of infection), fluid retention, allergies, hair loss and other side effects with taxol.
Prof. Powles."Both taxotere and taxol are still in clinical trials for use in operable breast cancer, so there are no proven benefits as yet, but they are both licensed for treatment in advanced breast cancer Taxotere is the one we will be using more as most trials use it. I give patients steroid cover for this drug as it has significant toxicity.
Haemopoietic Growth Factors
These stimulate the bone marrow to produce white blood cells (neutrophils). Most chemotherapy drugs can cause neutropenia which can lead to infections, and neutropenic scepsis which is potentially lethal. Blood counts are measured throughout chemotherapy and if anyone starts a fever they are put on antibiotics.
Haemopoietic Growth Factors stimulate the bone marrow to produce white blood cells
"This is what we have been doing," reveals Prof. Powles. "But if we give one of these haemopoietic growth factors, neupogen or neulasta, it pushes the neutrophil count right up and mostly prevents neutropenic scepsis and the use of antibiotics, It is all in the pipeline right now, but soon it may be possible to give chemo every two weeks (which is called a dose dense schedule), rather than every three. The trials so far show very encouragingly that this has a better effect on treatment. The side effects are also lower, so its likely to be coming into use in 2004."
Herceptin (trastuzumab) made by Genentech
Herceptin is the only antibody treatment currently available for breast cancer It is licensed in the UK to treat advanced breast cancer in women who over-express the HER2 gene. HER2 is a growth factor found on the surface of cells, that plays a key role in regulating cell growth. Some cancers produce extra HER2 receptors. This over-expression of HER2 causes cells to grow, divide, and multiply more rapidly. Herceptin seeks out HER2 and attaches itself to the protein receptor on the surface of cells, By binding to the cells, Herceptin has been shown to slow the growth and spread of tumours that have an overabundance of HER2 protein receptors. Herceptin is usually given intravenously in the outpatients department. It has been shown in studies to shrink tumours and extend womens survival by an average of about 13 months.
Side effects may include: weakening of the heart muscle, reduction of white blood cells (neutropenia), diarrhoea, anaemia, abdominal pain, infection or allergies. Some people receiving herceptin with adriamycin (doxorubicin) have experienced heart problems, because of the cardiac toxicity of both drugs. This combination is no longer recommended.
Prof. Powles says, "If a womans tumour is HER2 positive, the proven benefits of this drug are that the tumour will respond to treatment between 20 to 30 per cent better, with a survival advantage, compared to those who arent given it. If you give it in a combination with a taxol-type drug there is a better chance of survival than with just taxol alone. The results from trials, looking at giving herceptin to patients with primary operable cancer, should be through this year (2004) and my prediction is there will be a survival advantage there too. At the moment it is not licensed for use here in this way."
Endocrine Drugs
Anti-oestrogens Tamoxifen ( Nolvadex D, Soltamox, Tamofen) made by Astrazeneca
Tamoxifen has been the most commonly prescribed drug in the UK to treat breast cancer since its approval in the 1970s. It is given to pre and post-menopausal women. An anti-oestrogen, it blocks the oestrogen receptor and helps slow the growth and reproduction of breast cancer cells. In 1998, tamoxifen became the first drug to be approved by the FDA to prevent breast cancer after research showed it halved the chances of developing breast cancer in women at high risk of the disease. It is also used to treat other conditions, inciuding infertility. Tamoxifen is taken orally in tablet form or in a sugar-free syrup.
There has been a 30 per cent reduction in mortality from breast cancer since 1990
Side effects may include: hot flushes, irregular menstrual cycles, unusual vaginal discharge or bleeding, irritation of skin around vagina.
Rare: blood clots, cancer of the womb lining (endometriosis) an increased risk of stroke.
Prof. Powles says, "We have a huge amount of data on tamoxifen. We know that if we give it to patients with operable breast cancer, whose cancers are oestrogen-receptor positive, we will reduce the risk of relapse in pre or post-menopausal women and prolong survival. There has been a 30 per cent reduction in mortality from breast cancer since 1990- in spite of an increase in incidence - and tamoxifen is a major factor in that. It is a big drug. Theres always a big fuss about the side effects, but the overall benefits are real and significant so lets get it into perspective. Endometrial cancer is fairly rare, and most are curable. If you compare the numbers of endometrial cancers you get (something like one woman per 1,000) with the numbers of patientswho dont relapse its overwhelmingly in favour of preventing relapse.
The other problem is it can cause thromboembolism, but its the same risk as for oral contraception.
Anyone having major orthopaedic surgery should stop tamoxifen for three months. I also stop it for people going on long-haul flights. People with thromboembolism should not take tamoxifen. I would put them on an aromatase inhibitor or zoladex, if they are pre-menopausal."
Toremifene (Fareston) made by Orion
Similar to tamoxjfen, toremifene is an anti-oestrogen (SERM, selective oestrogen-receptor modulator). It is licensed here but hardly ever used as there is so much data on tamoxifen.
Side effects may include: hot flushes, nausea, weight gain, skin rashes, headaches.
Aromatase Inhibitors
Many breast cancers rely on oestrogen to grow. Post-menopausal womens main source of oestrogen is through the conversion of androgens (sex hormones produced by the adrenal glands) into oestrogens. This is carried out by an enzyme called aromatase. This conversion process is known as aromatisation and happens mainly in the fatty tissues of the body.
Anastrozole and letrozole work by blocking oestrogen synthesis. They reduce the level of oestrogen in post-menopausal women to very low levels.
Anastrozole (Arimidex) made by Astrazeneca
Anastrozole is licensed for use on post-menopausal women with operable breast cancer who cant take tamoxifen maybe because of problems with hot flushes or thromboembolism. It is taken orally. Clinical trials are currently underway to see whether women with advanced breast cancer would benefit more from taking anastrozole than tamoxifen. Cancer Research UK began a 10-year-study using anastrozole on 10,000 post-menopausal women with a family history of breast cancer to see whether it will prevent it.
Arimidex is taken orally
Side effects may include: hot flushes and sweats, tiredness, vaginal dryness, nausea, and vomiting, diarrhoea, hair thinning, headaches, vaginal bleeding (very rare and usually in first few weeks of treatment), joint pains/stiffness and increased or decreased appetite.
Long-term risk: osteoporosis.
Prof. Powles says, "It looks like anastrozole is more active at reducing the risk of relapse in patients with breast cancer than tamoxifen. We only have tour-year data at the moment, so we have to be careful on that. The trial was done on anastrozole, but theres probably nothing to choose between it and letrozole. There is some evidence that letrozole might be more active at reducing oestrogen levels. It has also been shown to be active after giving tamoxifen. Its not licensed for that use as yet but we could be using it after tamoxifen soon. Were not sure about long-term side effects of either of these aromatase inhibitors, because we dont have enough data, but they do increase the risk of getting osteoporotic fractures, and there may be other long-term effects of very low levels of oestrogen that we dont know about. If we are using it for advanced disease thats not so important, but if its for adjuvant disease, were using it because theres a better effect than tamoxifen or people cant take it. It seems reasonable to use it because the benefits probably outweigh the risks and we can give agents, including bisphosphonates, to prevent bone loss."
Natural progesterone works naturally with the body and can do the job better than these
drugs
Comment from Judy Evans. hormone expert and founder of the Progesterone Link Support Group: "I cant believe that this drug is being given to healthy women (in Trials). Anastrozole shuts down oestrogen production, which can cause osteoporosis. As Dr John Lee said, natural progesterone is accepted by the receptor sites and opposes oestrogen. It works naturally with the body and can do the job better than these drugs.
Letrozole (Femara) made by Novartis Oncology
Letrozole was approved by the FDA in 1997 to help treat advanced breast cancer in post-menopausal women whose breast cancer tumours have not responded well to tamoxifen. Letrozole works by reducing the total amount of oestrogen in the body (circulating oestrogen levels), thereby limiting the amount of oestrogen that can affect breast cancer cells. Recent publication of a trial has shown that using letrozole, after five years of tamoxiten, is more effective than continuing tamoxifen for women who have primary operable breast cancer.
Side effects may include: nausea and vomiting, tiredness and headaches, muscular aches and joint pain, hot flushes, difficulty breathing and hair thinning (see above for long-term risk).
Progestogens
Megestrol (megace) made by Bristol-Myers Squibb
Megestrol is used to treat advanced breast cancer, typically in women who do not respond well, or become resistant, to tamoxifen. It is a synthetic form of the hormone, progesterone and is taken orally. Progesterone is normally secreted by the corpus luteum of the ovary, and by the placenta, and acts to prepare the uterus for implantation of the fertilised ovum, to maintain pregnancy, and to promote development of secondary sexual characteristics. Progesterone also counteracts some of the negative effects of oestrogen (many breast cancers depend on oestrogen to grow and reproduce). In addition to treating advanced breast cancer, megestrol may also be used to treat advanced stages of endometrial cancer or to increase appetite in HIV patients.
Progesterone counteracts some of the negative effects of oestrogen
Side effects may include: fluid retention, weight gain, caused by the increase in appetite, and nausea. Women who have had blood clots or inflammation of a vein should tell their doctor before taking megestrol because it may affect the circulation of blood. There are very rare risks of allergic reactions, jaundice and raised blood pressure.
Long-term risk:osteoporosis.
(See natural progesterone below)
Ovarian Suppression
Zoladex (goserelin) made by AstraZeneca
Zoladex is a synthetic version of progesterone (a progestogen) and is used to treat early breast cancer in pre-menopausal women. It is suitable for women who have oestrogen receptor positive tumours. It is also used to treat pre-menopausal women with secondary breast cancer. It works by blocking the production of oestrogen. Zoladex is typically given by subcutaneous injection (under the skin) once a month. Zoladex is a systemic treatment; it cannot distinguish between normal cells and cancer cells.
Side effects may include: hot flushes, decreased sex drive and vaginal dryness. Most women will start their periods again within six months of their last zoladex injection, but in some cases women will go through early menopause.
Long-term risk: osteoporosis
Prof. Powles says, "This is the primary endocrine treatment for pre-menopausal women. I quite often use it when giving chemotherapy to switch the ovaries off, because I think it might protect them against the chemo. This is currently under clinical investigation."
Bisphosphonates
Bisphosphonates prevent short-term osteoporotic fractures
The following drugs are used on breast cancer patients, who are at risk of osteoporosis from use of oestrogen-blocking drugs. Bisphosphonates prevent short-term osteoporotic fractures. If people have too much calcium in the blood, hypocalcemia, the drugs also stop the bone releasing more.
Pamidronate (aredia) made by Novartis
Pamidronate is a nitrogen-containing bisphosphonate. Breast cancer has the potential to spread to almost any area of the body. After the axillary (armpit) lymph nodes, bone is the most common place to which it can spread. Pamidronate inhibits bone resorption by binding to bone, and it also inhibits osteoclast activity. Osteoclasts accelerate the breakdown of bone, which contributes to abnormally high levels of calcium in the blood that can overload the kidneys. Clinical studies have shown that patients on pamidronate tend to experience a delay in or reduction of bone pain, fractures, and other bone complications than patients who do not receive it. It is usually given intravenously.
Side effects may include: fever, fatigue, nausea and vomiting, initial bone pain, lack of appetite and anaemia (decrease in red blood cells).
Clodronate (bonefos) made by Aventis Pharma
As above, but can be taken orally or intravenously.
Side effects: diarrhoea or constipation, nausea and vomiting and rarely: breathing problems, mood or mental changes, muscle cramps, muscle shaking, problems with urination, throat sores, face, ankle or Hand swelling, and unusual heartbeat.
These drugs must not be taken at the same time as eating
Prof. Powles: "We did a 1,000-women study, giving clodronate to those with primary operable breast cancer, and we found that not only did it reduce the risk of bone loss, but also reduced the risk of them getting secondaries in the bones. Zometa (see below) is probably the drug thats most commonly in use at the moment. These drugs must not be taken at the same time as eating, and you have to be careful to give them over a period of time with intravenous fluids, because you can get renal toxicity if they are given too quickly."
Zometa (zoledronic acid) made by Novartis
As well as treating high calcium levels (HCM), zometa may soon be available as a treatment for several cancers that have spread to the bone, including breast prostate, lung, and multiple myeloma. Data from three clinical trials, involving more than 3,000 patients, have shown that zometa is more effective at preventing or delaying complications such as bone fractures, compression of the spinal cord, and severe bone pain than pamidronate. In the US, patients who were given zometa also experienced longer periods before re[apse than those who received pamidronate (30 days for zometa versus 17 days for pamidronate). Zometa can be given during a 15-minute infusion time, versus an infusion time of two to 24 hours necessary with the other.
Side effects for its use in HCM may include: fever, chills, bone pain, muscle of joint pain, nausea or vomiting.
All bisphosphonates work in a similar way - by restricting the
osteoclasts
Judy Evans says, "According to Dr Lee, bisphosphonates, like didronal which has been banned in America, Have many side effects. Fosamax is the most widely used on young women suffering osteopenia. All bisphosphonates work in a similar way, by restricting the osteoclasts. Osteoclasts resorb old bone, so if by restricting them you accumulate old bone, years later your skeleton is more prone to fractures. So all these drugs are doing, according to Dr Lee is delaying fractures. Natural progesterone is a precursor to the osteoblasts (that build bone) and there are many women using it who say that their osteopenic and osteoporotic conditions have improved without side effects.
Judy Evans ND has been an advocate of natural progesterone therapy and has been researching it since 1996. Judy is a naturopath and medical herbalist with her own clinic in Somerset.
Natural progesterone may be a safer option in the fight against breast cancer without any side effects
"I cant understand why women with breast cancer are given drugs with such damaging side effects when natural progesterone can do the same job without any.
Tamoxifen a weakly synthetic oestrogen, but it can cause endrometrial cancer and other side effects. Aromatase inhibitors, such as anastrozole and letrozole stop oestrogen being made, so its inevitable that any women on these drugs are going to get osteoporosis (see bisphosphonates).
Why give these drugs, including synthetic progestogens like megestrol when there is much evidence to show that natural progesterone may be a safer option in the fight against breast cancer without any side effects. Oestrogen a precursor to BCL2, which causes cells to proliferate; whereas progesterone is the precursor to the gene P53 which turns off the gene which causes proliferation."
For expert analysis on how natural progesterone works read "What Your Doctor May Not Tell You About Breast Cancer" by Dr John Lee ISBN: 0007142986.
For further information on natural progesterone cream, contact Judy Evans on: 01935 474343, or email her via: http://www.progesterone-link.co.uk/
Other articles of interest:
A review of Breast Cancer (described by one US cancer site as The best available - click here
Building an Integrated Therapy Programme -click here
Beware of taking too many drugs - Polypharmacy -click here