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Alternativas Contra el Cancer
Quimioterapia 3

What NOT To Let Your Doctor Do
by Larry Clapp, PhD, JD

When your doctor gives you a diagnosis of prostate cancer, he or she is also likely to tell you that you must have treatment immediately or you will die.

Surgery

If you're being treated by a urologist, a surgery called radical prostatectomy will probably be recommended. Also known as open prostatectomy, or simply the radical, radical prostatectomy is a major surgery which calls for your belly to be cut open and your entire prostate cut out. The theory behind the radical prostatectomy is deceptively simple: pluck out the entire prostate, cancer and all, before the cancer has a chance to spread.

If you're not careful, your doctor will have you believing that the radical prostatectomy is as simple and effective as using your spoon to scoop a little piece of hair out of your soup. If only it were true!

The surgery works only if the cancer is totally confined to the prostate, and not a single cancer cell has spread beyond it. Despite advances in testing, doctors cannot guarantee that a few cells haven't escaped the prostate. Many thousands of prostates have been surgically removed without curing the patient, for tiny bits of the cancer had already escaped. The surgeries were for naught and for many came at great sacrifices in quality of life.

Most men who undergo a radical prostatectomy end up suffering from varying degrees of impotence and incontinence. That's not surprising, given that the nerves controlling erection run right along the outside of the prostate. Even with the newer, "nerve-sparing" approach to the surgery, these precious nerves are often damaged or destroyed. Although some men recover to some degree, half or more of all men whose prostates have been surgically removed will never regain the ability to get and maintain an erection. And of course, there's a chance that you will die from the surgery itself.

But even if the radical prostatectomy worked more often and more effectively, it would still be ill-advised and dangerous. Why shock the body by cutting it when you can regain health without going under the knife? And the prostate is the center of a man's sexual energy when it's gone, his total energy is bound to lag. Look at and listen to men who have had the surgery. Ask your doctor for names of men who have had the surgery or, better yet, find a support group such as PAACT (Patient Advocates for Advanced Cancer Treatments).

Radiation Therapy

If, on the other hand, you happen to wind up in the hands of a radiologist, you'll get an entirely different recommendation. Since they've been trained to use radiation, these specialists urge their patients to undergo radiation therapy, also called radiotherapy or irradiation. The idea is to radiate cancerous cells to death, hoping to shrink and possibly eliminate the cancer. The radiation doesn't kill the cancer cells right away; instead, it "gets" them when they attempt to divide in two. If, however, the cancer has spread beyond the prostate, radiation therapy can only slow its growth. It will not cure you.

The standard approach has been to apply the radiation externally by "beaming" radiation right into your abdomen as you lie on a table. Radiologists will usually apply the radiation beam to an area larger than the actual cancer, just in case they've underestimated the size. If the cancer is localized in the prostate or the areas immediately adjacent, radiation treatment generally takes between six and eight weeks, five days a week. Common side effects of external beam radiation include incontinence, nausea, fatigue, diarrhea, radiation skin burns, and skin irritation. If the radiation damages the nerves that control erections (which run right by the prostate, touching the gland) you may wind up impotent. Of course, you can never be sure that the radiation "got" every single cancer cell in the body. If even one cell remains, the tumor can regrow, the cancer can spread, and all will have been for naught. And if the cancer does come back, you can't turn to radiation again, for too much radiation can actually cause cancer.

A newer approach to radiating prostate cancer, called internal seed radiation, uses tiny radioactive "seeds" surgically implanted in the prostate. Internal radiation refines the approach by getting the radiation right up against the cancer cells instead of passing it through the body and possibly harming other tissue along the way. The radiation seeds, which look like rice or bird seeds, are pushed through small needles right into your prostate. Fifty or more radiation seeds may be used on a typical patient.

Internal seeding has some advantages over external beam radiation. It's an outpatient procedure that takes only an hour to two. The seeds are placed right at or close to the cancer site, delivering their radiation "on target". Because the radiation is more focused than the external beam, there appears to be less risk of impotence and incontinence, and recovery takes only a day (or less). Andy Grove, CEO of Intel, elected to have seed radiation after researching the issues quite carefully. He wrote an outstanding article on the subject, called "Taking On Prostate Cancer" in the 5/13/96 issue of Fortune magazine must reading for anyone considering treatment of prostate cancer!

Hormone Therapy

Most men with cancer that is still confined to the prostate wind up undergoing either surgery or radiation. But if the cancer has spread, doctors will typically suggest hormone therapy. Hormone therapy is based on the idea that prostate cancer cells are especially hungry for testosterone, the male hormone. Take away this "food" and the cancer cells die. Most of the testosterone in a man's body is produced in the testicles, which is why doctors used to simply cut them off to "cure" prostate cancer. (The surgery to remove the testicles is called orchiectomy.)

But it's not enough to surgically remove a man's testicles, because the adrenal glands go into action to produce even more testosterone. So even after the testicles have been removed, a man suffering from prostate cancer must still take medicines to block the flow of testosterone from the adrenal glands. Another approach, which allows men to keep their testicles, is to use powerful drugs to block the flow of testosterone.

Whether a man keeps his testicles or not, hormone therapy deprives him of his usual testosterone. This slows the cancer somewhat, but has unpleasant side effects and undesirable psychological consequences. Men find themselves unable to get or keep erections, they lose muscle mass and gain breast tissue, and they suffer from fatigue hot flashes, reduced brain function, and other problems. Hormone therapy can be a helpful temporary measure to arrest or shrink the cancer.

Other Methods of Treatment

Although surgery, radiation, and hormone therapy are the medical system's favored approaches to treating prostate cancer, there are others. For example:

Cryosurgery is a relatively new procedure in which cancer cells, and the prostate they are in, are frozen to death. It is still considered to be an experimental procedure by many authorities. Although it's a "lesser" surgery than the radical prostatectomy, cryosurgery is still a major surgery that is a shock to the body. Impotence and incontinence are common. Other side effects include bleeding, infection, hypothermia, urethral-rectal fistula (which may lead to a colostomy), injury to the bladder or urethra, urgency and frequency of urination, and urinary retention. Cryosurgery is an effective alternative medical treatment that is far less invasive and just as effective as a radical prostatectomy.

Hyperthermia, the opposite of cryosurgery, is utilized separately and in conjunction with radiation. With hyperthermia, heat is applied to the prostate via microwaves coming from a cigar-box-like device placed between the man's legs or over his abdomen. No one knows quite how heat kills cancer. Some authorities argue that the heat damages the blood vessels leading to cancerous cells, without affecting normal cells, or that it kills the cancer cells weakened by radiation. Still others believe that heat interferes with the cancer cells' ability to make proteins or keep themselves "clean" but it is effective.

Chemotherapy uses powerful drugs to kill cancer cells. But the drugs don't specifically target cancer cells. Instead, they look for any rapidly growing cell. Cancer cells grow rapidly, but so do hair cells, cells lining the stomach, cells of the immune system, and cells in the bones. They, too, are killed by chemotherapy, causing a host of terrible side effects. Chemotherapy is not effective against prostate cancer per se; it's typically used only when the cancer has spread. And it's not a cure; it only helps relieve some advanced cancer symptoms.

Watchful waiting is recommended by some doctors (usually for older men) in the early stages of prostate cancer, before the tumor is big enough to "warrant" attack by surgery or radiation. Watchful waiting has the benefit of not assaulting the body, but it does nothing to stimulate the body's defenses. Many studies have found that watchful waiters match or slightly exceed the life spans of those who opt for surgery, and that the quality of their lives is far superior. (For more on this subject, read "Still Waiting, Watchfully" in the 5/13/96 issue of Fortune magazine.)

These interesting approaches may be useful adjuncts or substitutes for the traditional surgery, radiation, and hormone therapy, but they all miss the boat. None of them cleans the body of toxins and blockages, or strengthens the body's ability to heal itself and this process is the only way to successfully deal with prostate cancer.

WHAT SHOULD YOU DO?
Urologists argue passionately for surgery, while radiologists sing the praises of radiation therapy. Other physicians may insist that hormone therapy is the only salvation. Each specialist urges you to opt for their approach, insisting that it's absolutely the best thing to do, and that you should do it right now.

If your doctor tells you they have you scheduled for surgery or radiation tomorrow, or if they want to remove your testicles, start grilling them. Ask them to describe the side effects of these treatments, and the likelihood of suffering associated with each. Verbally pin them to the wall; make them defend their approach and show you the statistics that prove theirs is the best approach. Ask the doctors if their approaches help the body heal itself. If they are honest, they'll admit the answer is no. Ask for comparative analyses with other possible treatments. Get second and third opinions. Learn all you can.

After you've discovered the limitations of standard Western medicine, look into ways of cleansing your body and removing the blockages that encourage disease. Think about and visualize strengthening your body's ability to heal itself. Doesn't that make the most sense? If you agree that the best approach is to make your body strong enough to naturally and completely dispense with the cancer, keep reading. Then spring into action!

Implement your own healing plan. It can work, and it can work quickly: in 90 days! Remember, healthy bodies successful ward off cancer every day! Regularly monitor your progress. You can always fall back on your medical treatment of choice if necessary. (My unused fall-back choice was seed radiation.)



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QUESTIONABLE CURE

Bone marrow transplants have been giving hope to people with stubborn cases of breast cancer for years, but the effectiveness of the procedure has never been clear. A new study has renewed the debate.

The Health Unit is a partnership with the Henry J. Kaiser Family Foundation.


SUSAN DENTZER: Nine of Joanne Ruddy's eleven children gathered in a hospital room last month to wish their mother a happy 55th birthday.

KIDS SINGING: Happy Birthday, Dear Mom, Happy Birthday to you.

Unproved treatment?
SUSAN DENTZER: As she opened gifts and read cards from her two absent children, Joanne seemed eager to return home from Georgetown University Hospital after her latest bout of treatment for breast cancer.

JOANNE RUDDY: Thank you everybody -- a lot to look forward to when I get home.

SUSAN DENTZER: It's been almost a year since Joanne, a former school teacher, was diagnosed with inflammatory breast cancer. That is one of the most aggressive and least curable forms of the disease.

JOANNE RUDDY: "Dear Mom, everyone who still thinks you look terrific raise your hand"--

SUSAN DENTZER: Once the cancer was discovered, Joanne had chemotherapy to kill cancer cells that may have spread throughout her body. That was followed by a mastectomy and still more chemotherapy. Then, even as she celebrated her birthday, she was undergoing still another treatment -- doses of chemotherapy so powerful that they virtually destroyed her bone marrow, blood supply, and immune system. To keep Joanne from dying from the high-dose chemotherapy, special cells known as "stem cells" had been removed from her blood beforehand. They were mixed with a preservative and temporarily frozen. When the high-dose chemotherapy was complete, the cells were thawed. Then they were transfused back into Joanne Ruddy's body to help her bone marrow, blood supply and immune system regenerate.

HEALTH CARE WORKER: And then we're just going to do your vitals every fifteen minutes for one hour.

SUSAN DENTZER: Just days before Joanne Ruddy underwent the treatment last month, this same therapy made the news. Splashed across the front pages of the nation's leading newspapers were headlines like these. The stories reported on five major studies of breast cancer patients who had undergone similar high-dose chemotherapy and transfusions, known as "transplants". At first glance, most of the studies seemed to show little, if any, benefit from the procedure. Joanne Ruddy wasn't deterred.

JOANNE RUDDY: My doctor all along has told me that they don't have definitive answers, that they don't have enough information yet. I'm putting my trust in God that, you know, you have to take a chance.

DR. KENNETH MEEHAN: Hi! How's it going, okay?

JOANNE RUDDY: Yes --

SUSAN DENTZER: Joanne's physician, Dr. Kenneth Meehan, is a breast cancer transplant specialist at Georgetown.

A last resort.
DR. KENNETH MEEHAN: Most patients, in general, when they come to see me, they will do anything to try to live as long as they can without disease. Joanne, in particular, has a very large family, a number of children. She wanted to be very aggressive.

SUSAN DENTZER: That determination has hurtled Joanne into the midst of a raging medical controversy: How well -- and for which breast cancer patients -- do high-dose chemotherapy and transplants work? The debate constitutes a case study of the most difficult issues in medicine, where costly innovations offer new hope to the very sick -- however slim that hope may be. Dr. Lee Newcomer is medical director of United Health Group, one of the nation's largest health maintenance organizations. A cancer specialist, he has reviewed hundreds of cases of patients seeking high-dose chemotherapy and transplants.

DR. LEE NEWCOMER: I think the big issue is what's the right thing to do, and do we have some science and some evidence to tell a woman facing this decision what she really has to look forward to in terms of side effects, and in terms of outlook.

SUSAN DENTZER: A woman, that is, like Joanne Ruddy -- or like 49-year-old Sandra Rolef, who had a mastectomy for breast cancer several months ago. By that time, the disease had spread to 16 of her underarm lymph nodes, putting her at very high risk for a recurrence. Along with her husband, Rolef is now consulting oncologist, Dr. Robert Siegel of George Washington University. They are considering whether to go ahead with the high-dose chemotherapy and stem cell transplant.

DR. ROBERT SIEGEL: It's not a slam dunk one way or the other.

SANDRA ROLEF: So you're not ready to really make a final recommendation to me yet?

DR. ROBERT SIEGEL: I just think it's important not to jump to conclusions before you have to.

SUSAN DENTZER: Although Dr. Siegel is uncertain, other doctors Rolef consulted encouraged her to proceed.

"It's a kind of personal decision."
SANDRA ROLEF: One of the doctors said something to me that really is kind of sticking in the back of my mind, and she said, "You know, it's kind of a personal decision. And if you're the kind of person that wants to make sure that no stone is unturned, that you have done everything humanly possible to fight this disease and make sure that you're rid of it, then you should do it."

SUSAN DENTZER: The debate over the treatment's effectiveness has raged since the 1970s. Back then, high-dose chemotherapy and transplants were first used successfully to treat other forms of cancer, such as leukemia. Inevitably, doctors also began testing the approach in "advanced" cases of breast cancer in which the disease had spread to organs or bones. Such patients were given doses of chemotherapy drugs that were five to 30 times higher than those used in conventional treatment.

DR. LEE NEWCOMER: There was a lot of theory about the bigger the dose, the better the chance of getting rid of the cancer. By the middle 1980s this was a fairly common procedure.

SUSAN DENTZER: At the time, doctors used patients' own bone marrow for the transplants. They later switched to using blood stem cells when these proved just as effective. The treatment was costly -- as much as $200,000, or several times the price of more conventional breast cancer therapy. It was also very risky. Early on, as many as 1 out of 5 who got the treatment died from it, rather than from breast cancer. Besides the risks, there was also no hard scientific evidence that the treatment was effective. As a result, many health insurers balked at paying the costs. Breast cancer survivor Fran Visco is president of the National Breast Cancer Coalition, a group of 25 patient advocacy organizations.

FRAN VISCO: Physicians would say to women, a bone marrow transplant is the only thing that could possibly save your life. And you had situations where women sued insurance companies, requiring their company to cover a bone marrow transplant.

SUSAN DENTZER: The quest for treatment generated some of the highest-profile lawsuits brought against health insurers over the past decade. One involved this California woman, who sued her HMO, got the treatment, and subsequently died. In her case, as in others, courts ordered insurers to pay the costs.

FRAN VISCO: Well, insurance companies threw in the towel and started paying for bone marrow transplants broadly because of some of the verdicts.

But does it work?
SUSAN DENTZER: But there was still little hard evidence that the treatment worked -- the kind of information only gained from rigorous clinical trials. That's in part because assembling such studies was difficult. In a well-done clinical trial of this type, patients are randomly assigned to receive either the experimental treatment being tested or the standard, effective therapy. But many patients resisted entering trials, since they were convinced that the experimental treatment was their only hope.
DR. KENNETH MEEHAN: Patients nowadays are very intelligent. They do not want to be randomized to the chemotherapy line, despite my emphasis saying, 'We're not sure if this works at this point in certain situations. I would recommend this trial.' They would go elsewhere.

SUSAN DENTZER: Out of the estimated 12,000 women who underwent the treatment, only 1,000 participated in clinical trials.

FRAN VISCO: The real tragedy in this story is that if women had enrolled in the bone marrow transplant trials, if their physicians had encouraged them to do so, we would have had the answer years ago, and it would have saved lives.

SUSAN DENTZER: Gradually, though, major trials were assembled and began to accumulate results. One conducted from 1990 to 1997 tracked women with advanced cancer that had spread to organs or bones. After three years, the study showed no difference in survival rates between patients who got the new therapy and those who got the standard treatment. When this and other major studies made news last month, Sandra Rolef says --

SANDRA ROLEF: It had my telephone ringing -- lots of friends and family hysterical over it because of what the studies say. 'Why are you doing this, and, you know, why don't you just take your stem cells and freeze them and think about it?'.

SUSAN DENTZER: But the studies have not cleared up the controversy and they may actually have deepened it. On one side, Fran Visco's group argued that the procedure was fruitless.

FRAN VISCO: High-dose chemotherapy with bone marrow transplants for breast cancer is not an effective therapy.

Clearing up the controversy.
SUSAN DENTZER: But other cancer specialists argue that the results of the studies were far more ambiguous. Dr. John Durant is executive vice president of the American Society of Clinical Oncologists, known as ASCO.
DR. JOHN DURANT: It's way premature to say this strategy doesn't work. I think the strategy will continue to be of interest as a means of improving survival.

SUSAN DENTZER: To bolster their case that the jury on transplants isn't yet in, Durant and other specialists point to the complexities of the studies. One important factor is just how sick were the patients in the clinical trials. For example, the studies suggested the new therapy did not improve survival of patients with advanced cancer that had spread to organs or bones. On the other hand, the treatment looked more promising for patients like Sandra Rolef, whose cancer had only spread to 10 or more underarm lymph nodes. In one study conducted in South Africa, these high-risk patients who underwent the experimental therapy were far more likely to survive. Some of the clinical trials will now continue, and in addition, doctors say new studies are needed. For example, they want to know how effective the treatment is for other forms of breast cancer, such as the inflammatory cancer that afflicts Joanne Ruddy. They also want to understand the effects of treatment innovations that have taken place since the first studies began. For example, new procedures have cut the transplant death rate to as low as 1 in 20 patients. And powerful new chemotherapy drugs such as Taxol may also have yielded better results.

DR. KENNETH MEEHAN: I think that in the long run there will be a small advantage to transplant. It's not going to be 50, 60, 70 percent. It may be 10 percent, maybe a little bit higher.

SUSAN DENTZER: But Durant says it will be a while before those results are in.

SUSAN DENTZER: On a scale of one to ten, one being we know almost nothing about all of this, ten being that we know everything, where are we?

DR. JOHN DURANT: Oh, we're at two or three probably.

SUSAN DENTZER: The uncertainty raises the stakes for patients like Sandra Rolef.

SANDRA ROLEF: I don't want to look back in a year, or two years, or five years and say I should have, when they have more data, and maybe the data is going to end up saying that it does help. And how could I live with myself?

SUSAN DENTZER: After all, for Rolef, Ruddy and their families, the goal is living to celebrate more birthdays.

KIDS: All right! clapping

SUSAN DENTZER: The transplant studies will be a major topic of discussion next week. That's when cancer experts meet in Atlanta for ASCO's annual conference.



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La manera nosotros manejamos el cáncer del pecho y muchos cánceres no son en la actualidad ciertamente óptimos. . . . Mi hermano es un cirujano y yo digo a menudo que la cirugía es bastante bárbara y primitiva; claro él le dirá que la quimioterapia es aun más peor y yo no discrepo.

La quimioterapia tiene muchos efectos del lado. No es un tratamiento muy específico: penetra al arroyo de la sangre porque normalmente nosotros lo damos intravenosamente.

Afectará su cuerpo entero sus tejidos, piel, hígado, riñones, pulmones, cerebro son todos expuestos a estas toxinas cuando nosotros los introducimos en su cuerpo aunque nuestro propósito es afectar simplemente unas cuantas células o a veces un número grande de células.

Lo unico que podemos hacer es convertir al cancer en una enfermedad cronica, como la diabetes o la hipertención, pero no podemos cuararlo.

Dr. Simon Tchekmedyian, oncologo y profesor de medicina en la Universidad de Los Angeles.

Breast Cancer Chemotherapy: An Interview with N.S. Tchekmedyian, M.D.

N. Simon Tchekmedyian, M.D., F.A.C.P., is Associate Clinical Professor of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California, and practices oncology and hematology in Long Beach, California.

The way we manage breast cancer and many cancers at present is certainly not optimal. . . . My brother is a surgeon and I often say that surgery is quite barbaric and primitive; of course he'll tell you that chemotherapy is even worse and I don't disagree.

What are the main chemotherapy drugs used for breast cancer?

The main chemotherapy drugs used for breast cancer are idiomycin and Taxol or Taxotere. Those two compounds currently are the most important drugs and a close third is cyclophosphomide.

Are they effective?

They are effective. Chemotherapy for breast cancer works, and by that we mean it shrinks the cancer at least by 50 percent of its initial size. They work at least 70 to 80 percent of the time, meaning that if you have somebody who has either a large breast lump or has a growth somewhere else in their body, like the lungs or the bones or the liver, you give them these drugs and more than half of the time the cancer will shrink down by more than 50 percent.

It doesn't mean that the cancer is cured. In fact, I should say that if the cancer spreads outside the breast we do not currently have a cure for it. We can control it, often changing it into a more chronic pattern so that the person has a chronic illness like you have diabetes or hypertension or something like that, but you cannot really cure it and completely get rid of it.

How do chemotherapy drugs work?

Chemotherapy drugs work mostly by affecting the genetics of the cell. Cancer cells are immortal: they continue growing, they divide constantly as opposed to normal cells. Normal cells are born, they accomplish a function of some sort and then they die. The cancer cells are constantly dividing and that allows us to focus on them with these drugs. The drugs bind to the genetic material of the cell and when the cell tries to divide, instead of dividing it actually dies.

What are the most common side effects of chemotherapy?

When you talk about side effects of chemotherapy, one of the most important ones that I see as an oncologist is fatigue, just tiredness. It's like you get chemotherapy, you go home and you feel as if you were hit by a truck and you have to rest. Sometimes your family doesn't understand that. They want you to be active, they want you to fight your disease and you just are so tired and so weak that all you want to do is sleep and rest. It's important to recognize that it's probably the most frequent side effect of chemotherapy and it's pretty universal. It happens with most drugs.

There are certain drugs that have some specific side effects. For example, Taxol: that evening or the day after you are given Taxol you get joint pains, you get muscle aches, uh you feel very stiff. Nausea is not a problem with Taxol, but you get hair loss very often. Fatigue is a problem just as it is with all of the other drugs. Idiomycin, on the other hand, can give you mouth sores, can give you some nausea, and makes you very fatigued. It definitely make you have hair loss and if you give it at certain dose levels it can really cause a serious heart condition, with heart failure.

How do you choose which chemotherapy drug to use?

Oncologists have to work with drugs that have a lot of side effects and the ratio of efficacy to side effects is very narrow, so we tend to choose drugs that work well, that have a good level of efficacy and at the same time are well tolerated. When we have to choose which drug to use we look at the person, we look at, for example, what other conditions that person may have and then adjust the drugs that we choose to that condition.

For example, if somebody has breast cancer who is 72 years old and has had a couple of heart attacks you're not going with idiomycin because idiomycin can be toxic to the heart. If you have somebody who has a serious neurologic condition and severe weakness and problems with their nerves you may have a problem using Taxol because Taxol can cause neuropathy or nerve damage.

In terms of efficacy I think it's fair to say that idiomycin, Taxol and cyclophosphomide are the three most active drugs in breast cancer and clearly they are the front line choice in most cases.

How many do you have to choose from?

Oncologists have a fairly wide variety of drugs to choose from, and it goes into dozens but when you look at breast cancer in particular, there are just a handful of drugs that are truly effective, and these include Adriamycin, Taxol, Taxotere, cyclophosphamide. Gemcitabine (Gemzar) or vinorelbine (Navelbine) are other drugs that can be very useful.

How specific are these drugs?

Chemotherapy has a lot of side effects. It's not a very specific treatment: it goes across the board penetrating to the blood stream because usually we give it intravenously. It will affect your whole bodyall of your tissues, your skin, your liver, your kidneys, your urinary bladder, your lungs, your brainthey are all exposed to these toxins as we introduce them in your body although our purpose is to effect just a few cells or sometimes a large number of cells.

We have no way most of the time to specifically target those cells that need to be destroyed and spare the rest of the body. There are some situations where we can do this. For example, in ovarian cancer, if the cancer is completely into the abdominal cavity we can put in a catheter and instil the chemotherapy agent as a belly bath, so to speak . . . but most of the time we are affecting your whole body just to kill a few cells.

Let's say for example that you have somebody who had a breast lump removed and whose chance of having the cancer come back is about 50 percent. Well, 50 percent of the time we're going to give chemotherapy to that person and yet it's not going to help because that person may be cured to begin with. It's just that we have no way of telling. And in the other 50 percent of the time we will deliver the chemotherapy and yet get a benefit only in a fraction of those patients, so that maybe 20 or 30 percent of the time on those 50 patients out of 100 we will have efficacy. So when you take the whole group of 100 people, you may end up helping 10 or 15, but you have to treat 100 of them. It's just as non-specific as it gets.

How has chemotherapy changed in the last 10 years?

I have been in oncology now for about 20 years and since I started my fellowship back in the early 80's things have not changed all that much. We do have a few good new drugs that we can choose, particularly the taxanes like Taxol and Taxotere, important new drugs, but overall the side effect profile of the drugs [and] their mechanism of action are pretty much the same. We have not had a lot of advances in conventional chemotherapy over the last decade. I should say, however, that we have had major advances in some other areas of biologic therapy, including antibodies, gene therapy and a variety of other things.

Has the chemotherapy experience changed per patient in the last 10 years?

Although chemotherapy drugs still have a lot of side effects and we have not had great advances in terms of the drugs themselves, we have had major breakthroughs in terms of diminishing the side effects. We have much, much better treatments to prevent nausea now than we had 10 or 15 or 20 years ago; we have much better control of the immune effects of chemotherapy; we have ways of preventing and treating anemia associated with chemotherapy; we have ways of preventing the white cell counts from going down to dangerous levels.

We seldom if ever have to admit a patient to the hospital because of side effects of chemotherapy. We're able to control those side effects very well. The quality of life is better. Most of my patients who come here to be treated . . . come over, they read, they watch TV, they have a visit, they chat and joke with their nurses and their doctors, and then they go home, and most of the time they have very few acute side effects.

What is the most exciting new chemotherapy drug that's been developed in the last few years?

I would say the most exciting chemotherapy drug that has been developed for breast cancer over the last decade is Taxol and the taxanes, including Taxotere. These are drugs that have a different mechanism of action. They actually work by interfering with cell division because they bind to microtubules, small filaments that are involved in the process of cell division. That is a different mechanism than most of the drugs that actually bind to the genetic material of the cell. They were very toxic when they were first discovered and tested. In fact, the first few patients who were treated got so sick that the drugs were almost thrown away because they thought that they wouldn't be able to use them. . . . Their efficacy is very high and we have learned how to use them and therefore they are very well tolerated.

Why do some drugs work for some patients and not for others?

It can be quite frustrating to try to control a cancer both for the patient and the doctor . . . Some cancers are inherently very resistant to chemotherapy and some others become resistant after a period of treatment. The reason why the cancer cells become resistant has to do with mutations or changes in their genetic material. As they divide, cells become progressively more derailed in the way their genetic material works and the more this process takes place, the more these cells become oblivious to the presence of these drugs around.

These genes are important in terms of telling the cell what to do, telling the cell how to behave. When this gene changes because of so many divisions and so many mutations, then the behavior of the cell becomes completely abnormal and that leads to resistance to drugs that normally kill cells.

So what's your strategy when you're giving chemotherapy drugs to a patient and it doesn't work on that patient? How do you decide what other drugs to try?

Generally we use the drugs with the higher level of efficacy and the lower level of toxicity up front and then as the cancer becomes more progressive and more resistant we have to go into drugs that perhaps are more toxic but that still have a chance of working, or we go into drugs of the lower levels of efficacy but used in a lower dose to approach what we call palliation.

So you're juggling dosage with a mixture of different drugs?

The choice of chemotherapy drugs for breast cancer is somewhat empirical and based on our knowledge and experience, but we usually can have a fairly rational and sound approach as to the selection of different drugs as we manage the patient. Many years and many decades of experience with drugs and different patients have shown us what works best and what should be used first and what should be used second and so on.

There are some tests available where you can take fresh cancer tissue and test it to see what drugs work betterwhat's called chemosensitivity assays. Unfortunately so far the results with these tests have been sub-optimal and they cannot be trusted. Most oncologists do not do those tests because they have not proven to result in improved patient outcome results.

How do you decide when to give chemotherapy in conjunction with surgery at the moment?

A one centimeter small growth contains a billion cells. It takes, we think, approximately eight years for a growth that size to show up in the breast. During those eight years and before you've reached that level of one billion cells. Many of those cells have penetrated into the blood stream and have been circulating around. Some of those cells will be knocked down by the immune system or some other factors and disappear, but some of them may survive and find a new place to livein the bone marrow inside the bones, in the liver, in the lungs, in the lymph glands or somewhere else, so when the surgeon cuts the breast open and takes a lump out, what we're taking out is what we see, the lump that contains the billion cells with some normal tissue around it, so that we get rid of the primary illness.

The problem with breast cancer is not that lump. The problem with breast cancer is the cells that left that lump and have been circulating around that can grow later on into new cancers, so-called metastasis. By using the combination of primary surgery with chemotherapy we approach the local problem and the systemic problem of those cells that have escaped, so chemotherapy used together with surgery makes a lot of sense. We've been doing that for many years and the results clearly show that we can cure patients who otherwise would have died of breast cancer by using chemotherapy as an adjuvant to surgery.

Not every patient who has a lumpectomy or a mastectomy also receives chemotherapy. How do oncologists decide that?

Well, you decide it on the basis of what the probabilities are that the cancer will come back, that the cancer has spread. What are the factors that we pay attention to? Well, the size of the cancer is very important. Tumors that are very small (less than one centimetre, less than half an inch in diameter) generally have a good prognosis. Tumors that are larger than one centimetre, particularly if they are larger than 2 centimeters, over an inch, are more serious. Tumors that have cells that look very wildwhat we call poorly differentiated cellshave a much higher chance to grow back. Tumors that penetrate into nearby small lymphatic or vascular channels tend to behave worse, and the presence of an abundance of certain genetic markers indicates that the cancer is more aggressive.

We know that cancers in young women tend to be more aggressive and they tend to come back more, and we know that we have to be more proactive and more aggressive in the treatment of younger patients. The so-called estrogen receptor and progesterone receptor, which have to do with the presence of compounds on the cell surface that indicate that the cells are sensitive to the female hormone estrogen also influence our course of therapy. The ones that have the receptors tend to have a slightly better prognosis.

So we put all of that information together and we try to come up with what is the probability of a cancer growing back in the future and recurring. Based on that probability we then decide whether chemotherapy is necessary.



So it might be necessary for someone who has a negative lymph node biopsy?

Oh, absolutely. Initially we used to apply chemotherapy when the risk of recurrence of the cancer was very high, so that we would use chemotherapy for patients who had a lump in the breast and had lymph glands under their arm that were involved. Under those circumstances the probability that the cancer will grow back with surgery alone is over 50 percent and chemotherapy reduces that risk fairly substantially.

As we were able to use drugs with a little better toxicity profile and as we were able to manage the side effects of chemotherapy better we started using chemotherapy in patients who have just a primary lump but no other invasion of lymph nodes or any other sign of spread. We now do so because by studying these patients we've learned that chemotherapy also improves the cure rate in those patients who have a lump in the breast without invasion of the lymph nodes.

Are there many patients at this stage receiving chemotherapy who shouldn't be receiving chemotherapy or for whom chemotherapy has no effect?

One of the factors that women use to try to decide whether to have chemotherapy or not for early breast cancer is determining what exactly will be the improvement. How can you quantify that improvement? My experience and some published reports indicate that if you ask women, you'll find that if the improvement in the chance of having the cancer come back exceeds 3 to 5 percent they will take it.

Now what do we mean by 3 to 5 percent? Well, if you take a hundred women with breast cancer and if the probability that the cancer will come back for each of those women is, let's say, 15 percent, and if you can lower that probability from 15 percent to 10 percent with chemotherapy, women will decide to take it. What does that mean? Well, it means that you're going to have to treat a hundred women to help five.

Do you find that's a great shame?

As a medical oncologist I see patients who have cancer and who need treatment, and my job is to provide everything that I have available to reduce the odds that that person is going to die of cancer. My job is to make sure that the person understands what the options are, and that we use those options wisely so that we improve the cure rate and maintain the quality of life and the function of that person.

When you're facing somebody with primary breast cancer, perhaps with a small lump in the breast and no lymph node involvement, you can say, well, the probability that this person will be cured with surgery alone without chemotherapy is 70 percent, and the probability is about 30 percent that this cancer will come back.

We have treatments such as chemotherapy that will improve that chance of recurrence from 30 percent down to 20 percent. We have no way of telling whether that particular person is the person who will benefit from it, so my question to that woman is "there are two buses leaving town. The women in one bus are going to have a 20 percent chance of recurrence and the women in the other bus are going to have a 30 percent chance of recurrence. Which bus do you want to take?"

So the issue is not as much about the fact that how non-specific and how toxic it is. The issue is what I face every day: this is what we have today, this is the best we can do today. I'm sure we'll be doing much better in ten years, but this is what we have to do now and that's my job: to help women make a decision as to what's the best choice today.

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