SURGERY
RADIATION THERAPY
CHEMOTHERAPY
IMMUNOTHERAPY
INVESTIGATIONAL TREATMENT
ALTERNATIVE OR UNCONVENTIONAL TREATMENT

There are four conventional primary methods to treat a cancer: surgery, radiation, chemotherapy, and immunotherapy. There are four goals of treatment: cure, prevention, prolongation of survival, and palliation. Palliation means that treatment is given to remedy a symptom of the cancer without being able to treat the cancer itself.

SURGERY

Cancers that can be cured surgically usually must be localized. This means that they are in an early stage and that they are only in one place. The place where they are must be removable with a good margin of normal tissue. The cancer must be a type that has little potential to spread to other parts of the body. The regional lymph nodes are also usually removed during the surgery. A cancer of the cervix that is confined to the cervix is an example of a cancer that can be treated surgically. The surgery is a radical hysterectomy and removal of the pelvic lymph nodes. The word radical means that additional surrounding tissue is removed with the cervix. The breast can also be removed by radical surgery which means removal of the breast and the adjacent underlying tissue. Radical removal is necessary if a cancer is to be cured surgically; that is, there must be a wide margin of uninvolved tissue removed with the cancer.

Surgery may be the initial step in diagnosis and treatment but not be curative itself. Other methods of treatment such as radiation or chemotherapy would be the primary treatment. Ovarian cancer is usually diagnosed surgically. The surgery is seldom sufficient as complete treatment and additional treatment with chemotherapy is then given.

RADIATION THERAPY

Radiation therapy is given by several different methods. In general, radiation is used when a region of the body is to be treated. External radiation treatment refers to treatment to an area of the body by exposing it to a beam of X-rays. The treatment takes only a minute or so and is repeated each day, usually for about 20-25 treatments. The X-rays penetrate the body and deposit energy in the tissues. This deposition of energy causes injury to the cells in its path, the normal as well as the cancerous. Some are killed, some are injured and repair themselves and some are not affected. Those that are able to repair themselves are re-irradiated with the next day's treatment. Again, some are killed, some injured and some unaffected.

The normal cells are also injured but are able to repair themselves better then the cancer cells. Thus the cancer cells are selectively killed more than are the normal cells. The amount of energy deposited in the cancer is called a RAD. This means Radiation Absorbed Dose. A typical radiation regimen may deliver 200 RADs per day, 5 days per week for 5 weeks. The dose would be 5,000 RADs. Recently the unit RAD has been changed to the Gray (Gy). One RAD is equal to one cGy (centigray); one hundred RADs are equal to one Gy.

Radiation therapy is also administered by radiation implants. Other terms for this are: intra-cavitary implant, interstitial implant, radium implant, cesium implant, high dose rate insertion, needle implant, and some that are named for the developer of that particular technique. The overall term is brachytherapy which means slow therapy. These implants are placed in the cancer itself or right next to it and are usually left in place for several hours or several days and then removed. The implant is loaded with a radioactive source that gives off radiation to the surrounding tissue while it is in place. Brachytherapy is a method for giving very high doses of radiation to a specific implanted site while sparing the surrounding tissues.

The amount of radiation administered is determined by the tolerance of the normal tissues that are also irradiated. Standard doses for specific areas of the body have been developed by past experience. A dose can be given that will kill all cancers but will probably also kill patients. A dose can be given for which there will be no side effects but which also probably will not cure anybody. There is always a trade off: the probability of cure Vs the risk of complications. Radiation complications mainly depend on what normal tissue is being irradiated. There are common side effects for each major area of the body being irradiated.

X-rays are not the only type of external irradiation. Electron beams are used in special circumstances. Other particle beams are being used mostly in the research setting.

CHEMOTHERAPY

Chemotherapy is the type of treatment that everybody associates with the loss of hair. This is common but by no means inevitable. It mostly depends on the specific drug being given. Chemotherapy is treatment by anti-cancer medicines given by injection into the blood stream or by pill. With certain limitations, it goes to all parts of the body and can treat cancer in any location. Almost all chemotherapeutic agents act by interfering with cell division. Cancer is the result of uninhibited cell division. If the cancer cells can be prevented from dividing then the cancer will not grow. Normal cells also must divide to replace those lost through wear and tear as well as to repair tissue injuries. These normal cells are also affected by the chemotherapy. Chemotherapy is also referred to as cyto-toxic therapy.

All chemotherapeutic agents have side effects. Many have specific side effects characteristic of that drug. Some have major toxicity to the heart, some to the kidneys, and some to the nerve tracts. Almost all are toxic to the bone marrow which is responsible for the production of the white and the red blood cells and the platelets. The white blood cells: granulocytes, monocytes and lymphocytes are primarily responsible for fighting infections. The platelets are necessary to prevent bleeding. Those chemotherapeutic agents that are toxic to bone marrow cause a drop in the white cell count after each course of chemotherapy. The lowest count is called the nadir count. It is expected that the white cell count and the platelet count will go down and that they will return to normal so the next dose of chemo can be given.

Until recently there was nothing to do but wait for the bone marrow to recover. Now there are drugs that can be given to stimulate the bone marrow to produce more white cells. If the white cell count gets too low, then infections can occur which may be fatal. If the platelet count gets too low then spontaneous bleeding can occur from various parts of the body. The red cells are not affected as much. They are responsible for carrying oxygen. Over a period of time there may also be a drop in the red cell count which could cause symptoms of fatigue. Occasionally a blood transfusion may be necessary.

Nausea is a common side effect of chemotherapy but there are now several very effective drugs that can be given to prevent this. For most people it is no longer a major problem. The cells lining the mouth and digestive tract are actively dividing to replace those that are lost every day. Injury to the lining of the intestines and mouth can result in ulcerations that must heal before more chemotherapy can be given. Some drugs affect the skin, so sun exposure should be avoided.

Once chemotherapy is started it is usually repeated for a predetermined number of courses. It is continued as long as there is no evidence that it is not working, or until the predetermined number of courses has been given. Then a decision is made to either stop or continue with some sort of maintenance dosage. There are standard regimens that are used to treat each type of cancer. These regimens have been determined by studies comparing various treatments. The standard treatment represents the most effective treatment known at that time. When other regimens or new drugs are developed they are compared with the standard treatment and if found to be better become the new standard, or best known treatment.

The doctors who are specialists in chemotherapy are called medical oncologists. They go to meetings at least every three months where they are told about new and wondrous drugs or rearrangements of old drugs so they are never at a loss as to what to recommend. The doctors who specialize in radiation therapy are called radiation oncologists. They go to meetings also and in the last twenty years have changed the unit of dose from RAD to Gray [Gy]. They are imperturbable and thoroughly predictable whereas the medical oncologists are an unruly and tempestuous lot.

IMMUNOTHERAPY

Immunotherapy as a treatment for cancer has been tried in one way or another for about one hundred years. Except for a small number of rare cancers it has not become a major treatment modality. Theoretically it could be a perfect treatment by mobilizing the body's own weapons to kill cancer cells. There is a tremendous amount of research being done, but so far little of clinical value has been produced.

The immune system provides the body protection against infection and invasion by foreign material. The major components of the immune system are the white blood cells. The lymphocytes make a variety of chemicals that provide for antibodies against infecting organisms. They also provide for the rejection of foreign material such as a skin graft from a non-matched donor. Some lymphocytes when properly stimulated can kill other cells. If that other cell is a cancer cell then it can be destroyed by the lymphocyte. Another type of white cell, the granulocyte, primarily destroys bacteria and viruses and is directed to do so by antibodies.

The immune system functions primarily by recognizing what is self and what is not self and destroys that which is non-self. If a cancer cell were sufficiently different from a normal cell so as to be recognized as non-self then it would be destroyed. This is the rationale for the tremendous expenditure of research activity into immunotherapy as a cancer treatment.

INVESTIGATIONAL TREATMENT

There are many investigational studies being done in cancer treatment. These studies can be divided into three types. In a Phase I trial a new treatment is being studied. It has already been studied in animal trials and now needs to be tested in humans. The purpose is to determine the dose levels and side effects. To be eligible there must be no known treatment for the cancer. Usually these are patients who have progressive cancer despite all known effective treatment. Once the dosage, side effects and administration problems are worked out the next step is a Phase II trial.

In Phase II trials the treatment is offered to patients with a variety of cancers. And, again, there must be no other known treatment for the cancer. These patients have progressive cancer that is essentially untreatable. The purpose of Phase II trials is to determine if the treatment has any benefit. If it demonstrates activity against a certain type of cancer then it will be compared to the most effective known treatment in a Phase III trial.

In Phase III trials the investigational treatment is compared to the most effective known treatment. This will require that the treatment be randomized which means that the treatment given to a particular patient is determined by chance. There are several methods to provide for randomization. The goal is to have each treatment arm contain the same sort of patients with respect to extent of disease, age, past treatment, etc. Although it sounds easy it is always a challenge to see that each treatment arm contains patients with the same characteristics. Many a study has been proven worthless because of this failure. If the investigational treatment is superior to the conventional treatment then it becomes the conventional treatment.

Should you participate in an investigational treatment? For the Phase I and II trials there isn't much to lose, provided you still wish to be treated. The Phase III trials can be a problem because you want your doctor to recommend what he thinks is best and he is ethically obligated to do so. In the Phase III trials he doesn't know which treatment is best. If that makes the patient uncomfortable they shouldn't consider a Phase III trial. Just be aware that some of our most useful drugs came up the ranks of investigational studies and that those patients benefited.

ALTERNATIVE TREATMENT

Alternative or unconventional treatment is called alternative or unconventional because it has not been shown to be effective. Were it effective, it would be the conventional treatment. To be proven to be effective usually requires a randomized study comparing one treatment against another. There is always some reason why this has not or cannot be done by the promoters of unconventional therapies. The National Institutes of Health has an office to study many of these unconventional therapies. They have funded grants for several millions of dollars to evaluate a variety of these therapies. If any are proven helpful there will be a stampede to report it. There is no conspiracy to suppress a known cure. If any of the dietary, lifestyle, or thought manipulations being promoted actually were effective then that discoverer would have been awarded a Nobel Prize ten years in a row.

Claims for the effectiveness of these types of treatments are never more than testimonials. A testimonial is nothing more than an unsubstantiated assertion of one's belief. It proves nothing, only what one believes.

Conventional treatment is the result of the scientific process. A problem or phenomenon is studied. An hypothesis is made and experiments done to confirm or reject the hypothesis. The human body and its workings are incompletely understood. There is more unknown than known about it. But, even with this lack of knowledge the scientific process has yielded huge benefits to us. There are no alternative antibiotics, insulin, blood transfusions or x-rays. There are no advocates of alternative electricity, electronics, aerodynamics. refrigeration, chemical engineering or physics. Everything you have that the caveman didn't have is the result of the scientific process.

The reason that there are unconventional therapies in medicine and none in any other field of applied science is that medicine is an inexact science. And, everybody is going to die of something sooner or later. There is no avoiding it. There is no scientific way to stop it. Excluding accidents and trauma, everybody is going to develop an illness which will be fatal. They may be able to avoid or cure one or several illnesses, but they will get another one sooner or later that will be untreatable or incurable. It will happen to everybody. Since there is no scientific way to avoid it and since nobody wants to die there is nothing else to do but to try anything. This assures a large, continually renewing population of desperate people.

Unconventional therapies can be useful in certain circumstances. They give hope where none is otherwise expected. They allow the patient to participate more and to take more control over their treatment. Unconventional therapy should not take the place of conventional therapy as long as there is scientific proof that the conventional treatment may be helpful. Unfortunately, there are many situations in which it has been scientifically proven that conventional treatment will not be helpful. In these situations the options are no treatment, investigational scientific studies, or unconventional treatment. At this point the decisions are philosophical not medical.

William M. Rich, M.D.
Clinical Professor of Obstetrics and Gynecology
University of California, San Francisco
Director of Gynecologic Oncology
University Medical Center
Fresno, California