Drug treatments

Unlike surgery and radio­therapy, drug treatment is ‘whole body’ treatment. Anti-cancer drugs are carried by the bloodstream to almost every part of the body. Thus it is possible for drugs to kill cancer cells wherever they are. Drugs are particularly useful, therefore, in the treatment of cancers that have spread from the original tumour to other parts of the body, or when there is a significant chance that they may have done so even though this cannot be detected.

There are three possible reasons for giving anti-cancer drugs:
1 To try to destroy the cancer by the drug treatment alone, aiming for a complete cure.
2 To try to improve the chance of cure by eradicating any residual microscopic disease left behind after surgery or radiotherapy, or by shrinking the cancer suffi­ciently to make these treatments easier or more successful (adjuvant treatment).
3 To try to shrink the cancer sufficiently to achieve symptom improvement or prolongation of life.

There are two main categories of drugs that are used to treat cancer: cytotoxic and hormonal (‘endo­crine’). Cytotoxic (cell poisoning) drug treatment is commonly known as ‘chemotherapy’. Chemotherapy often has a significant effect on normal cells as well as cancer cells, potentially resulting in a variety of side effects. In contrast, hormonal treatments are usually much ‘gentler’. However, chemotherapy is active against a far wider range of cancers than hormonal treatment and it also tends to act rather more quickly. Different people with the same type of cancer will often respond very differently to the same treatment, whether hormonal or cytotoxic.
It is important to remember that some anti-cancer drugs can interact with other drugs. The doctor responsible for your anti-cancer treatment should be made aware of any other medication you may be taking.

CHEMOTHERAPY

Chemotherapy works by interfering with ‘mitosis’ (cell division). Just like radiotherapy, if it is completely successful in stopping cancer cells dividing, the tumour will eventually disappear as its cells die of ‘old age’ without being replaced.
Cytotoxic chemotherapy, rather like radiotherapy, is particularly active against both cancer cells and normal cells that are dividing. When chemotherapy is successful, its effect is often seen most quickly in cancers where the cells were dividing rapidly beforehand. Similarly, the side effects tend to be prominent in those tissues or organs where the normal cells are usually dividing quickly. These include the bone marrow where the blood cells are made, the hair follicles and the inner lining membrane of the bowel.
As with radiotherapy, giving chemotherapy involves trying to strike the right balance between killing cancer cells on the one hand, and avoiding intolerable side effects on the other. Fortunately, con-siderable advances have been made in recent years in lessening the side effects of chemotherapy, which are now much less troublesome than many people imagine. Indeed, some forms of chemotherapy now cause virtually no unpleasant symptoms whatsoever. Somewhat surprisingly, friends and relatives still occasionally lead patients to expect chemotherapy to be much more unpleasant than it really is.
Some other medicines can interfere with chemotherapy. The oncologist responsible for your treatment should be made aware of all other medicines that you may be taking.
There are many different cytotoxic drugs and a vast number of combinations of them. They are used to treat a wide range of different cancers and in a variety of circumstances. Some types of cancer respond in general much better than others. Also, individual drugs vary considerably in how well they work against particular cancers. Although space here is too limited for a detailed description of chemotherapy for any particular cancer, you can obtain further information from some of the sources listed under ‘Further help’.

Combining drugs

A proportion of the cells of any cancer is likely to be resistant to a particular individual drug, even if that drug is very effective against the remainder. This is why most chemotherapy involves taking combinations of drugs in the hope of lessening the chance of treatment failure because of resistance. Also, lower doses of individual drugs can be used in combinations than might be needed if they were being given singly, and this can sometimes lessen particular side effects.
When prescribing ‘combination chemotherapy’ your doctor will aim to choose drugs that tend to be active against your particular cancer, but which have rather different side effects. The chosen regimen may also incorporate drugs that interfere with different stages of cell division. However, the chosen combination will ultimately be based on its track record in treating large numbers of people with the same kind of cancer in the past.

Having chemotherapy

Sometimes chemotherapy may be taken by mouth (‘orally’), but more often it is given by injection into a vein (‘intravenously’ or ‘IV’). Having a chemotherapy intravenous injection started usually feels just like having blood taken for a blood test. You might feel a coolness or other unusual sensation in the area of the injection.
You will probably have chemotherapy intermittently, say once every three weeks or twice a month, in the outpatient clinic. Usually it is administered as a single injection or ‘infusion’ (using a ‘drip’) into a vein on the hand or lower arm over a few minutes or sometimes over several hours. Sometimes injections are repeated daily for a few days, and sometimes the drug is infused continuously over a day or a few days, with two-to three-week intervals in between courses. There are very many different treatment schedules.

You may need to stay in hospital if you are having more intensive and toxic treatments. Infusional chemotherapy quite often requires you to be treated as an inpatient on the ward, although it is possible to administer some drugs by con­tinuous infusion at home using a small pump strapped to the body. This method is used particularly for those patients who are treated by continuous infusion over prolonged periods.
If you need prolonged infusions or very frequent injections you may have a ‘central venous catheter’ or ‘line’ inserted. These are thin flexible tubes which have their inner end positioned in a large vein inside the chest and the other end outside, so that drugs can be injected into it. The outer end may be on the front of the chest (Hickman or Groshong catheters) or in the arm in the case of ‘peripherally inserted central catheters’ (‘PICC lines’) which are put in via an arm vein. Sometimes the outer end of the catheter is not brought out through the skin but is attached instead to an ‘implantable port’, a barely noticeable small container placed surgically just underneath the skin of the chest wall. Injections are then made through the skin into the port. These ports are not suitable for everyone, but those who do have them find that they don’t interfere much with normal life. You have to be in hospital to have the catheter inserted, but you will then be able to go home once it is in place. Very occasionally chemotherapy is given via a catheter inserted into an artery directly supplying a cancerous liver or limb.
Each individual period of chemotherapy administration, whether given in a single injection or over a few days, is commonly known as a ‘course’, although sometimes single injections or infusions are called ‘pulses’. This type of treatment should always be given by specially trained staff, and these days you will usually be treated by a highly qualified nurse.

How long does chemotherapy last?

Just how long your chemotherapy treatment will continue depends on a number of factors. When given with the aim of cure or as an ‘adjuvant’ (aiding) treatment there will probably be a clearly defined duration (provided of course there is no evidence that it is not working satisfactorily), based on past clinical experience and research. It may be as short as a couple of months or occasionally up to a year or even longer. When the aim is to relieve symptoms or prolong life, how long the treatment lasts depends very much on the effect of treatment on the cancer and on any side effects.

Side effects

These days many people find that chemotherapy causes few serious problems and, although you will probably experience some side effects, these are often not at all severe. They vary enormously according to the drugs and dosage used and your general health. There are, however, some side effects that are quite common to a large number of drugs. The gaps in between treatment courses allow the normal cells to recover, particularly the bone marrow cells, which are generally more sensitive than other normal cells to chemotherapy.

• Effects on the blood and why blood counts have to be checked
The bone marrow produces the blood cells, of different types. The red cells carry oxygen around the body, the white cells fight infection and the platelets clot the blood to seal leakages in blood vessels. A deficiency of red blood cells is known as anaemia. A deficiency of white cells is called ‘leucopenia’ and ‘thrombocytopenia’ is a deficiency of platelets.
Most cytotoxic drugs interfere temporarily with bone marrow function, particularly the production of white cells and platelets. Bone marrow toxicity is the most common and generally the most important side effect of chemotherapy. The concentration (‘level’ or ‘count’) of the white cells and the platelets in the blood will usually fall during the week or so after chemotherapy, the extent depending on both the drug(s) used and the dosage.
Once leucopenia reaches a certain severity, you are at an increased risk of getting an infection and your immune system is less able to deal with it. For this reason, you will probably be advised to try to avoid close contact with people with infections, or with children who have recently received immunisation with a ‘live’ vaccine. You may also be advised to pay extra attention to personal hygiene, dental and skin care, and to avoid squeezing pimples as this can release bacteria into your bloodstream. Such precautions are especially important if you are receiving particularly intensive treatment. Patients who are having or have recently had chemotherapy should check if it’s all right for them to have any immunisation themselves. They will usually be advised to avoid ‘live’ vaccines (those containing living organisms).
If you are having chemotherapy, you should always tell your doctor immediately if you have any signs of an infection, particularly a fever, chills or sweating. If this happens your blood count will usually be checked straightaway. If your white cell count is below a certain level, you will probably have to have ‘broad-spectrum’ antibiotics intravenously to help your body’s own immune system fight off the infection, while waiting for the count to recover.
Very occasionally, thrombo­cytopenia becomes so severe that you start to bleed or bruise very easily and, again, you should report this to your doctor promptly. If necessary you can then be given a transfusion of platelets from donated blood while waiting for your marrow to recover. If your platelet count is low you must make every effort to avoid even minor injuries. Anaemia caused by chemotherapy is usually a much less urgent problem. However, it can cause skin pallor and symptoms such as weakness, tiredness and breathlessness.
Normally the blood count recovers fairly rapidly, but it is important that it has returned to normal by the time you have your next course of treatment. If not, it is usually necessary to postpone further treatment until the count has recovered, and sometimes it is then decided to reduce the chemotherapy dosage. If further chemotherapy were to be given when the count was already low, there would be a greatly increased risk of serious complications. This is why your blood count is checked routinely before each course or pulse of chemotherapy.
Occasionally ‘growth factor’ (also known as ‘colony-stimulating factor’ or CSF) injections are given after chemotherapy to stimulate the recovery of the white cells, and similarly ‘epoetin’ for red cell recovery, although anaemia is usually readily correctable by blood transfusion.
Sometimes marrow-stimulating ‘growth factor’ (also known as ‘colony-stimulating factor’ or CSF) injections are given after chemotherapy to hasten white cell recovery, and similarly epoetin may be given to boost red cell production, thus possibly avoiding the need to correct anaemia by blood transfusion.

• Sickness
Nausea and vomiting are well-known side effects of chemotherapy, but they are now much less of a problem than they used to be. Several drugs cause this only to a slight degree, if at all. If you are taking drugs that cause more troublesome sickness, the problem can usually be prevented or greatly lessened by modern antidotes. Anti-sickness drugs (called ‘antiemetics’) are now often given routinely to stop symptoms developing, sometimes starting the day before the chemotherapy is given (see ‘Nausea and vomiting’).

• Hair loss
Another well-known and common side effect is hair loss or ‘alopecia’, although not all drugs cause it. Hair is sensitive because the cells in the hair follicles divide rapidly. Sometimes alopecia is only slight, but with some drugs it becomes virtually total. Some patients also experience transient scalp tenderness. Hair loss usually begins about two and a half weeks after the start of treatment. Hair always regrows once chemotherapy is completed, usually starting to do so about three weeks after the last course. You may find that at first your hair is curlier than before. Occasionally some regrowth occurs during chemotherapy. Hair loss can occur on all parts of the body, but it is the hair on the head that is affected most.
Fortunately, society’s attitude to hair loss has changed considerably in recent years, perhaps partly as a result of changing fashions and partly because we are all more used to seeing and reading about people who have lost their hair after cancer treatment. Although you may well be understandably upset at the thought of losing your hair, you will probably find that in reality you cope with it better than you expected.
If you’re not happy to leave your head uncovered (although increasing numbers of people are), you should choose a wig or hair­piece before your hair starts falling out. It’s usually a good idea to shave off your remaining hair or at least cut it short once it starts coming out significantly.
You may be offered the option of a technique called ‘scalp freezing’ to try to lessen hair loss. It involves wearing an extremely cold cap for some time before and after a chemotherapy injection. The cold causes the scalp blood vessels to constrict, thereby reducing the drug supply to the hair follicles. It’s not suitable for everyone and, although it can work well for some patients, it’s not always successful. It does prolong considerably the time involved in receiving chemotherapy and it can be uncomfortable.

• Other side effects
Many people feel a little unwell for a day or two after chemotherapy, or sometimes for longer. Tiredness is also common and occasionally it can last for quite a long while after treatment. Most side effects stop fairly quickly, but some can be persistent and very occasionally permanent.

A rare side effect of chemo­therapy is skin damage at the site of the injection. Some drugs have the ability to cause quite serious ulcers if they leak out of the vein into the surrounding tissues. These days, the staff who administer your chemo­therapy are highly trained and take the utmost care when giving drugs, but this problem can still happen very occasionally. Tell whoever is giving your injection immediately if you experience any pain or discomfort at the injection site while the injection is proceeding, as this may be the first indication of a leak.
Chemotherapy with some drugs can stop the ovaries or testicles working normally. This can result in impaired fertility or infertility, and some women may have an early menopause. Deep-frozen storage or ‘cryopreservation’ of sperms (‘sperm banking’) is offered to younger men about to receive treatment that may render them infertile. Cryopreservation of embryos is a possible option for some women faced with losing their fertility. This requires the use of fertility drugs to stimulate their ovaries to produce eggs which are then fertilised in the laboratory by sperms from a partner or donor. Another option is cryopreservation of non-fertilised eggs, but this has a very low success rate.
There are many other potential side effects of chemotherapy, some being peculiar to particular drugs. However, it’s also true to say that most people either don’t experience them or don’t find them unduly troublesome, or find that they can be satisfactorily treated or even prevented. All side effects are more likely and more severe in people who are receiving more intensive treatment. They include mouth ulcers, sore eyes, cystitis, diarrhoea, nail changes, numbness of extremities, rashes, slightly impaired concentration and memory, and depression. Very rare side effects include lung, heart or kidney damage, and causing another cancer to develop many years later. Always report any troublesome symptoms during treatment – quite often there is something that can be done about them. Of course, not all such symptoms are in fact caused by the chemotherapy and other possible causes may need looking into.
Reading about all these possible side effects can be alarming if you are about to undergo chemo­therapy, but it’s worth stressing that many people are able to continue with normal life and work for much of the time in between chemo-therapy courses. Indeed, those who do so often seem to cope better with it all. Most people say that chemotherapy was rather less troublesome than they had anticipated.

Bone marrow and stem cell transplants

Sometimes chemotherapy is given in very high dosage, with a massive effect on the bone marrow. Such intensive treatment is suitable only for people with some types of cancers, particularly the leukaemias and the lymphomas. It has such a profound effect on the blood that the person being treated needs to be ‘rescued’ by being given a bone marrow or stem cell transplant. This makes it feasible to give much higher doses of chemotherapy than would otherwise be possible, thereby improving the chance of a cure for people with some cancers.
If you are having a bone marrow transplant using your own marrow, it must be removed before intensive chemotherapy. Alternatively, it may be taken from a ‘donor’ whose marrow matches yours very closely. A close match is important, otherwise it will be ‘rejected’ later by your immune system. Many donors are close relatives, usually brothers or sisters, but unrelated donors can also sometimes provide marrow that is a good match. The removal or ‘harvest’ is done by inserting a special needle into the marrow of the bones at the back of the pelvis under general anaesthetic. Only a fairly small proportion of the total marrow is removed, leaving ample to meet the donor’s immediate require­ments. It is replaced fairly rapidly by replication of the remaining marrow cells. The removed marrow is frozen and stored until given to you via a drip into a vein after the high-dose chemotherapy. The marrow cells then find their way via the bloodstream to your bones, where they start to manufacture blood cells again.
An increasingly preferred alternative to a bone marrow transplant is what’s called a ‘stem cell transplant’. This involves removing from your own blood­stream marrow cells (or stem cells) that have been stimulated to leave the marrow by injections of growth factors. A drip is put into a vein in each arm. Blood is taken from one arm into a machine that removes the stem cells and it is then returned via the other drip. The whole procedure takes three or four hours. The stem cells are frozen and stored until they are given to you via a drip when required.

HORMONAL TREATMENTS

Some cancers depend on hormones for their growth. Hormonal treatments work by preventing cancer cells getting or using the hormones that they need. They tend to have much less effect on normal cells than chemotherapy. However, hormonal treatments are effective only in the treatment of the relatively limited range of cancers that are potentially susceptible to hormonal influences. These are principally those of the breast and prostate, but occasionally cancers of the thyroid and the inner lining of the uterus (‘endometrium’) will respond to hormonal treatment. Hormonal drugs are often given in tablet form. They work more slowly than chemotherapy and may need to be taken for some months for any effect to become apparent.

Breast cancer

Tamoxifen, which works by blocking the mechanism by which the hormone oestrogen encourages cancer cells to grow, is by far the most commonly prescribed drug for women with breast cancer. If given as an adjuvant treatment following surgery it can improve the chance of cure. Adjuvant tamoxifen is usually recommended to be taken for five years. It is mainly effective for those women whose cancer can be shown on laboratory testing to be ‘oestrogen-receptor’ positive. An oestrogen receptor (also known as ‘ER’ because of the American spelling ‘estrogen’) is a complicated chemical molecule found in large amounts on the surface of some cancer cells.

Most women tolerate tamoxifen well, but it can sometimes cause side effects such as hot flushes, slight weight gain and vaginal discharge. Very infrequently it can cause vaginal bleeding. If you develop this you should tell your doctor so that the reason can be investigated. The cause is usually some benign thickening of the inner lining of the womb but very occasionally there may be an early cancer requiring surgery.
As well as being used as an adjuvant treatment to increase the chance of cure, tamoxifen has a very valuable role as a palliative treatment. For some women it can relieve symptoms and keep cancers under control for long periods of time. There are a variety of other hormonal drugs that can also be used which have the same aim and there is now evidence that some may be slightly more effective than tamoxifen. They include anastrozole, exemestane, letrozole and toremifene, all given daily in tablet form, and goserelin given by injection beneath the abdominal skin once a month. All palliative hormonal treatments for breast cancer tend to be more effective against slower growing cancers.
In general these drugs cause few problems, but some women do experience side effects such as mild nausea, hot flushes and slight hair thinning. Although hormonal drugs can keep cancers in remission for long periods in some women, there is a tendency for them eventually to become resistant and escape control. However, if a woman has responded well to one of these drugs, there is quite a good chance that she will respond well to another if the disease relapses.
There is some evidence that tamoxifen may have a role in preventing breast cancer in women at high risk of the disease, but this is currently controversial.

Prostate cancer

This type of cancer is usually highly responsive to hormonal treatments that stop male sex hormones stimulating the cells to divide. At one time this was best achieved by removing the testes, an operation known as ‘bilateral orchidectomy’. The same effect can now be achieved, however, by using one of a closely related group of drugs including goserelin and leuprorelin, which in ‘slow release’ form can be given by injection beneath the abdominal wall skin just once every three months.
These drugs can, however, occasionally stimulate cancer growth in the period immediately after they are first given. This effect can be blocked by taking one of the ‘anti-androgen’ group of anti-prostate cancer drugs, such as flutamide or cyproterone, in tablet form shortly before the first injection and for about three weeks afterwards.
Hormonal treatments for prostate cancer are usually well tolerated but they can cause loss of sexual desire and impotence. They are quite often recommended for men with more advanced cancers that are not suitable for surgery or radical radiotherapy, but they can also be used to shrink down a primary cancer to try to give the surgery or radiotherapy that is to follow a better chance of success.

Other agents

Drugs can be administered that sensitise tissues to damage by a particular type of light emitted from a special type of lamp or laser. After administration of the drug, the light can be directed where it is needed, and laser light can be transmitted down fibreoptic cables that have been introduced into hollow organs and even directly through tissues into deep-seated tumours. The maximum effects of this treatment, known as ‘photodynamic therapy’ or PDT, can be focused accurately and PDT is proving to be very useful in treating cancers and pre-cancers involving the skin, oesophagus, bladder and lung. It can eradicate completely small superficial growths and it can provide useful palliation for selected patients with advanced cancers.

A number of treatments have been developed that are intended to destroy cancer cells using the same mechanisms by which the body’s immune system is able to fight infections. Complex chemicals such as interferon or interleukin, which are normal components of the immune system, can be manufactured and administered in high dosage by injection. Side effects can be troublesome, for example, flu-like symptoms, but they show useful anti-tumour effects in a proportion of patients with some of the rarer types of cancer, including lymphoma, myeloma, some types of leukaemia, AIDS-related ‘Kaposi’s sarcoma’, kidney cancer and melanoma.
Just as the body produces complex ‘magic bullet’ chemicals known as antibodies to destroy invading bacteria or viruses, it is now possible in the laboratory to manufacture antibodies that can ‘target’ very specific components of some particular types of cancer cell. This has led to exciting new treatments using either the antibodies by themselves, or combinations with other toxins or radioactive substances to make them more effective. They can be used to carry ‘enzymes’ to cancer cells. These enzymes can then convert inactive ‘pro-drugs’ given to the patient into active cytotoxic drugs in high concentration, just where they are needed. They can also be used in conjunction with chemotherapy. Allergic reactions are quite common, but treatment with antibodies has now proved to be very useful in the treatment of some particular types of lymphoma and breast cancer.
Using vaccines to stimulate the immune system to fight the cancer is an experimental approach that is showing some promising early results, particularly in bowel cancer and melanoma.
Research in recent years has identified many types of protein molecules present within cancer cells which are crucial components in the highly complex processes that cause these cells to behave malignantly. Novel types of drugs have been produced that interact with these proteins and disrupt the cell’s chain of command. They are now beginning to be used successfully, as in the treatment of one type of chronic leukaemia. Rapidly growing knowledge of the many processes involved in malignant change and behaviour will inevitably lead to many more novel drug treatments in the fairly near future.