Kevin Murphy, MD is a medical oncologist practicing in Vancouver, BritishColumbia. Dr. Murphy has an intense interest in empowering his patients throughinformation, and he wrote Adjuvant Chemotherapy to help hispatients with their most common questions.
Adjuvant chemotherapy is the use of drugs as additional treatment forpatients with cancers that are thought to have spread outside their originalsites. This type of treatment has been very successful in changing thebehaviour of certain cancers such as breast cancer, testicular cancer, ovariancancer, just to name a few. In order to understand how this type of therapyworks and in some cases, doesn't work it would be worthwhile to outline a fewimportant points.
First of all, one of the most confusing concepts for patients is visualizinghow small cancer cells really are. When we reflect back on high schoolbiology, we might remember what a cell looks like diagrammed on a textbookpage; much, much larger than life. We might remember looking at onion cellsunder a microscope which magnified them so we could see how they wereorganized. But, it is very hard to understand the problem of cancer withoutfirst realizing how very, very tiny cancer cells are. Perhaps the best way tounderstand this is to reflect back to a religious question posed hundreds ofyears ago by very learned scholars. They pondered, if God were truly allpowerful, and He could make angels, and make them very small; then, how manycould dance on the head of a pin ? Needless to say, this question is still notresolved. However, it can be said with some certainty that cancer cells are notangels !! We can estimate that approximately one billion cancer cells wouldmake up a lump with the diameter of one centimeter (about half an inch). If thehead of a pin is about one millimeter (one tenth of one centimeter) in diameterthen approximately one million cancer cells can make up a lump the size of thehead of a pin. Visually we can look at the situation this way:
Why is it important to focus on how small cancer cells are ? Because when apatient has been told by their surgeon...."we got it all", then it isimportant to remember that cancer cells are quite capable of "hiding"out of sight from the surgeon's view. Therefore, the expression "we got itall' only applies to that cancer the surgeons are capable of seeing.
Whenever a patient is reviewed after an operation and advised to undergovarious tests, there is an assumption that if the tests are negative, thenthere is no cancer present elsewhere. In reality, what the negative tests meanis that there is no detectable cancer present. Given thesmall size of cancer cells, it is quite possible that many cells are"hiding" out of view.
Does this concept mean that cancers are never cured with surgery orradiation ? That everyone with cancer has tiny deposits lurking out of sightwaiting to come back and strike a person down ? No. What we know is thatsome people are at risk of having cancer cells"hiding" out of sight. It is these people who may be suitable toreceive adjuvant chemotherapy.
What follows next is an explanation for adjuvant chemotherapy that is fairlyconsistent for any type of cancer. The exact details of treatment will changein terms of drugs dosages, side effects, etc. The general concepts will be thesame.
The usual approach is to start after the patient has been "workedup". This means that all the necessary tests designed to look for cancerelsewhere have been done and they are normal. As stated earlier, this justmeans that the tests can't find any cancer. It still may be lurkingaround somewhere else in the patient's body. Are there different amounts foreach patient? Yes. Are all patients at the same "starting point" ?The answer is No. Everybody is different.
Fig 2.
In the above diagram, the Y (vertical) axis represents the number of cancercells that can develop with continued growth of a cancer. The two horizontallines represent the number of cancer cells that can be found by a physical exam(visible by exam) and the next one down represents the number of cancer cellsthat be found by tests , such as bone scans, CT scan, X rays,etc (visible bytests). Any number of cancer cells below the test line is undetectable(invisible).
From the above diagram you can see two round circles, A and B. A representsthe number of cancer cells that are present in patient A and B represents thenumber of cancer cells in patient B. Both patients have surgery which removesall visibly detectable cancer. For example patient A had a large lump in herright breast measuring 4-5 cm in diameter. Patient B had a smaller lump about1-2 cm in diameter removed from her left breast. After the surgery bothpatients were investigated with various tests to see if any residual cancercould be detected. None was. If you look at the circles labelled A and B aftersurgery you can see that patient A has a larger amount of cancer cells leftover than patient B. Both amounts , however, are still below the "testline" and therefore are not detectable ("invisible"). Bothpatients are eligible for additional treatment such as adjuvant chemotherapy.They may have the same treatment which can kill many millions of cancer cells.The chance of cure, however, will be better for patient B since the number ofher residual cancer cells is less than patient A.
Although generally speaking, the larger the cancer at diagnosis, the greaterthe chance of more cancer cells left behind (patient A's cancer), thisrelationship is not always true. Some patients have cancers that do not developthe ability to migrate elsewhere (metastasize). These can become large andinactive. Other patients have cancers that develop the migrating ability earlyin their growth before they can be found on examination or even screening.These migrating cells can grow enough to prevent additional treatment frombeing useful.
Once the treatment has been started, it is usually impossible to tellwhether it is working. This is because we are dealing with very small cellsthat are scattered around the body, too small in number to find and hiding inrelatively large organs. What is usually done is to check periodically that thecancer has not "broken through" the treatment. We know that certainlab tests are better at finding cancer than a physical examination. Therefore,on a regular basis, a few tests can be done to check the situation. This maymean only blood tests, or perhaps an X ray.
Fig 3.
The above diagram is similar to the one above (Fig. 2). It differs however,in that it is designed to show what can happen during adjuvant treatment. Theround circles represent the number of residual cancer cells for three patients.For example, patient A has residual cells left behind after surgery andthey are sensitive (S) to the treatment (they can be killed). Therefore, with 6cycles of treatment patient A is cured. Patient B has some cancer cells whichare sensitive to treatment and are killed during the early period of therapy.Some of the cells, however, are resistant (R) to treatment (cannot be killed)and they become the majority of the cancer cell population. This populationthen grows undetected until it can be found by lab tests, and then byexamination. Patient C has resistant cancer from the very beginning. By doingchecks with each treatment it becomes very clear that by treatment 5 the canceris growing and further treatment for patient C is of no value.
Once treatment has been completed, many patients ask what "checkups" will be done to ensure that the cancer hasn't come back. This bringsup a difficult problem. As discussed earlier, the use of tests to find verysmall amounts of cancer cells is limited by the ability of the tests.Therefore, a negative test does not mean the absence of cancer cells. It justmeans the test is negative. In addition, if a test is positive, and is accurateat detecting cancer as a cause for the positive test, then what is next? If atest shows the presence of cancer deposits in an organ like the liver, whattreatment do we have to get rid of the cancer ?
If adjuvant chemotherapy is used to destroy "left over" cancercells, then we would use the best possible drugs to do the job. In other words,send in the "A team", to borrow an expression from the sports world.If this treatment is not successful, then we can expect that the cancer cellsstill alive after the initial treatment will be resistant to the first linedrugs (the A team). This usually implies that the cancer cells will beresistant in part to second line drugs (the B team). Therefore, there is verylittle chance that further treatment will provide a cure. This is particularlytrue for patients with the common cancers such as breast, lung, bowel andprostate cancer. Some less common cancers can be cured after they come backwith very aggressive treatment which may include bone marrow transplantation.
Given the current therapy available, it makes more sense to follow patientsusing clinical methods (a thorough history and physical) rather than usingtests. If a patient develops symptoms that are related to recurrent cancer,then treatment can be directed towards helping the patient feel better. If apatient has cancer that has recurred but is feeling well, then there is notreatment which will help the patient feel better. Rather, the treatment, withits side effects, may make the patient feel worse.
[Editor's Note: Dr. Murphy makes a lucid argument here, but there are alsoother points of view. In the US, at least, it is common for patients to receivemore aggressive follow-up than what Dr. Murphy describes here. As in many areasof medicine, not everyone has the same philosophy. Similarly, oncologists andpatients may have different philosophies and strategies for dealing withrecurrent cancer, and, of course, it depends greatly on the individualsituation, and on the patient's wishes. - Steve Dunn]
Many patients, after adjuvant therapy, feel unsure of what to look for inthe way of symptoms. Since they are actually healthy people it is helpful torealize that all the usual colds, flus, aches and pains will affect them justlike anybody else. If their cancer is to return and cause problems, then theproblems that need treatment will be symptoms that just don't goaway, like the common cold, the flu, or the usual aches and pains fromeveryday life.
Adjuvant chemotherapy for cancer is a difficult treatment to understand. Asone patient said: " You are suggesting that I have treatment which willmake me temporarily unwell, to treat cancer that you can't find, and can't besure you have eliminated even when treatment is finished". That is whatadjuvant treatment is about. It is similar to life insurance. When you pay yourpremiums to the insurance company, you are recognizing a potential risk to yourlife that may or may not happen (car crash, sickness, earthquake, hurricane,etc.). Treatment with adjuvant chemotherapy is designed toreduce the risk of cancer returning. Large scale clinical trials haveshown significant benefit from adjuvant therapy for patients with breastcancer, colon cancer, testicular cancer, lymphomas, etc. However, like so manythings in life, adjuvant therapy does not come with a written guarantee. Inspite of this "no guarantee" clause; when the length of time ontreatment along with its side effects are balanced with the possible benefitssuch as a longer life, then for most patients eligible for treatment thebenefits usually outweigh the risks.
Paging Dr. Murphy... Paging Dr. Murphy... Kevin - ifyou find this, please update me on your email address - I get requests for itnow and then!
联系客服
