Sorry ladies, more chemotherapy is better after surgery for breast cancer

Every 5 years, a group known as the Early Breast Cancer Trialists’ Collaborative Group (ECBTCG), publishes a summary of all the studies of treatment of women after breast cancer surgery. Early on they showed that tamoxifen post surgery saved lives, chemotherapy saved lives and also pointed out how long each of these treatments should be given.

Now, 25 years after they started producing these reports, this group, based in Oxford, England has come up with another summary of recent studies (Lancet 2012, page 432). In this one, the major finding is that adding a taxane (paclitaxel (Taxol) or docetaxel (Taxotere) to standard chemotherapy after breast cancer surgery saves even more lives than the standard chemotherapy regimens.

Early in my practice, I would give a course of three drugs (cyclophosphamide, methotrexate, and 5-fluorouracil) to certain women who had a good chance of recurrence of their breast cancer after surgery. Later, I would use a regimen that contained the drug Adriamycin – reports (like the ECBTCG)had shown this was slightly more effective.

About the time I left practice, the taxanes were developed. These were drugs that amazingly were first extracted from Yew trees. Later, they were synthesized by pharmaceutical companies. Eventually they were tested in women with breast cancer and proved effective. Ultimately they were added to the chemotherapy regimens given to women after breast cancer surgery.

The big question was whether they made a difference. The answer, according to the EBCTCG is they do. If they are added to a standard course of treatment with a regimen containing Adriamycin or drugs like it, they save lives. The EBCTCG found that after 8 years, out of 100 women treated with taxane, 3 more were alive compared to women who didn’t receive the drug.

The problem is that adding taxanes prolongs the treatment. They are given after the standard chemotherapy regimen so that the standard treatment, which normally takes about 3-4 months, is now longer by another 3 or more months. If the standard chemotherapy is given for a longer period, the difference isn’t as great, but there is still a difference. Either way, women need to get added chemotherapy for a longer period of time.

Bottom line: More is better. Fortunately taxanes are not terribly toxic. But they are still chemotherapy and no one feels great while taking them. So if you are receiving chemotherapy after breast cancer surgery, plan on more time under the weather.

It’s time to stop getting that PSA test for prostate cancer

I was reminded of this when I learned of a new article “hot off the press”, published in the Journal of the National Cancer Institute. The news was so exciting that they published the results online before the journal was released. And what was so exciting? We learned that screening for prostate cancer doesn’t save any lives.

The study described in the article was the Prostate, Lung, Colorectal, and Ovarian Screening trial (PLCO). I already wrote about the Lung cancer part of the trial (CT scanning), which worked; CT scanning saved lives. But the Prostate cancer trial (PSA testing and rectal exam) did not.

Here is how the trial was done. Men were randomly assigned to either screening with yearly PSA testing (Prostate Specific Antigen – found in the blood and goes up if there is prostate cancer) and rectal exam to feel for nodules in the prostate gland, or just routine care. Now the routine care may or may not have included the prostate cancer screening. It wasn’t supposed to, but who knows? There were about 37,500 men, 55-74 years old, in each arm of the study.

At the time this paper was written, 3815 cancers were found in the usual care group and 4250 in the men that were tested. There were very few deaths in either group. In the screened group 158 men died of prostate cancer, while there only 145 prostate cancer deaths in the men who weren’t being routinely tested. No significant difference. Perhaps the most convincing evidence that screening doesn’t work is that the lead author of the paper is a urologist, a surgeon who operates on prostate cancer. Urologists are the only national group that still recommends screening.

All this work echoes another article published last year in the British Medical Journal summarizing all the studies on screening for prostate cancer. This one included trial of nearly 400,000 patients, some of which were in the PLCO study. This paper also found that screening did not save lives.

Maybe there isn’t a clear-cut benefit. What’s the downside to screening? The treatment. Surgery, radiation, and drugs can cause sexual difficulties, urinary problems and in general, not a happy life. And if you are diagnosed with prostate cancer, even if your doctor says it is low grade and doesn’t need surgery, this is hard for most men to live with and they eventually will opt for treatment and take their chances with the side effects.

Screening should save lives. If it doesn’t, then it isn’t worthwhile. This is especially true in prostate cancer where the side of effects of the treatment can be devastating.

So do as I do say (and do), stop taking the test.

Don’t believe the headlines about Avastin

Today’s LA Times published an article that headlined “Drug is promising for ovarian cancer”. The article referred to two separate studies published in today’s New England Journal of Medicine (Dec 29,2011). My dictionary says that promising means “showing signs of future success”. I just read the articles and think their results have closed out the chances for the future.

Here is the basic information. Most cancers that arise in the ovaries (about 80%) are detected late because they don’t cause symptoms till they are large or have spread. Many attempts at developing means to detect them early have failed; there is no good screening test. The five-year survival for these women is around 30%. About 15,500 women will have died of this cancer in 2011.

So there is a definite need for better treatments. Today’s reports presented information on the drug Avastin. Avastin represents a new approach to treating cancer. It doesn’t aim for the tumor, but rather is directed against the blood vessels that supply the cancer. As the cancer grows, it needs to stimulate new blood vessels to supply it with nutrients. Avastin is designed to block this. It is controversial because it is expensive, has some serious side effect (though not more serious than other cancer therapy, only different) and hasn’t been that effective. Recently the FDA withdrew its approval of Avastin for treating breast cancer after initial successes proved temporary and were trumped by its serious side effects.

So it is a drug looking for a disease to treat. It has won approval for treating colorectal cancer and some forms of lung cancer, but even in those diseases, the results are not something to celebrate. Today’s reports on its role in ovarian cancer are likewise not something to celebrate. In fact, they are downright discouraging. In one study, from the U.S., nearly 1900 women with advanced ovarian cancer were studied; half received standard chemotherapy and the other half got Avastin in addition to the chemotherapy. It took a little longer for the cancer to progress in the Avastin group (and one must always be cautious about this because progression of ovarian cancer is often tough to spot), but after four years just as many (a little over half) of the patients who received Avastin had died, as did patients who did not get the drug.

Another study of over 1500 women with ovarian cancer was published in the same issue of the journal. This study was mainly done in Europe and had the same results. The cancer took a little more time to progress in the women given Avastin, but after 3 years, the groups had equal numbers of deaths.

What does all this mean? It means that blocking blood vessels with a drug like Avastin, though a great concept, isn’t the answer to ovarian cancer or most other cancers, unless there is a better blocker out there somewhere.

I have always said that the main treatment for cancer is surgery. All the other treatments like chemotherapy and radiation make much less difference than does surgery – cutting it all out. Ovarian cancer, as well as most other cancers, is curable if caught early. Perhaps we need to spend out money on learning how to catch, not treat.

The world’s third most deadly cancer is becoming a greater problem here.

Every year, about 700,000 people die of liver cancer. I am referring to cancers that start in the liver, not those that have spread there. Spread to the liver is a very common problem in patients with cancer. But, in my practice, I rarely saw cancers that started in the liver. That may change for newer generations of American oncologists.

Most liver cancer is found in developing countries, particularly in Asia. Half of all cases are diagnosed in China where the rate of liver cancer is about 5 times that in the U.S. Most of the liver cancers in China are caused by infection with hepatitis B virus. But this should become less of a problem in the future. We now have a vaccine to protect against infection with this virus and the number of liver cancers caused by this virus will drop.

In the U.S., we are not seeing a drop in liver cancers even though immunization against hepatitis B is becoming widespread. In fact every year the number of cases increases by around 4 percent. This year, it is expected that 20, 000 Americans will die of this disease. This puts liver cancer in the top ten of killer-cancers.

So why are we seeing an increase in liver cancer? One main reason is infections with the hepatitis C virus. We can immunize against hepatitis B virus, but not hepatitis C virus. That vaccine hasn’t been developed although I am fairly sure lots of drug companies are trying to develop one. Hepatitis C, like hepatitis B virus is transmitted by blood and sex. Now our blood supply is almost completely free of the C virus, but having unprotected sex with a carrier or shooting up with drugs has become the major way this disease is transmitted.

Another common cause is alcoholism. Big time drinkers develop cirrhosis, which can eventually lead to liver cancer if something else doesn’t kill these imbibers. Because they often smoke there is a big chance other cancers will take them away first.

And there is a new kid on the block causing liver cancer, part of the deadliest epidemic to strike us recently – obesity. When I was growing up, NASH stood for an automobile manufacturer, now extinct. Today it stands for Non-Alcoholic SteatoHepatitis. This is also known as fatty liver although the two disorders are slightly different. But now we are seeing these people develop liver cancer at a faster rate than healthier thinner fellow Americans. And as we all know, obesity is a problem that isn’t going away and I suspect that this cancer won’t either.

Unfortunately, liver cancer is usually fatal. Most people with this cancer die. The five-year survival rate is around 15 percent. This low rate has not been helped by periodic screening with ultrasound of the liver and blood tests that can detect the disease at its earliest stages.

It is unfortunate that while the numbers for many cancers are improving, it isn’t happening for liver cancer. This is mostly a self-induced disease. And we have added a new cause, obesity, to the old causes of hepatitis from unprotected sex, intravenous drug use, and alcoholism.

Breast radiation after cancer – I was wrong

Often in my practice, women would ask after their lumpectomy for breast cancer if they really needed the proscribed radiation therapy. I always said yes. It would lower the chances of the cancer returning in that breast. But, I didn’t think it was life-saving. So I wouldn’t worry if older women wanted to opt out. The radiation was a lot of trouble. Daily visits over the course of 6 or 7 weeks was a major effort for them. And, after all, their tamoxifen should lower their chance of a recurrence.

I was wrong. This week (Nov 12) in the British journal Lancet, a group of researchers from Oxford analyzed all the work ever done on the benefit of radiation therapy to the breast after lumpectomy. They found that not only does it lower the chance of recurrence in the breast, it also lowers the women’s chance of dying from the disease. And this applied across the board. Old women, young women, on tamoxifen, off tamoxifen. No matter what the situation, radiation was better than no radiation.

All the studies these researchers analyzed were head to head studies that compared women who received radiation after lumpectomy to those that didn’t. In general the rate of recurrence was lowered by half in women who received the radiation. Most of these recurrences were in the breast that had the cancer. But recurrences elsewhere were also lowered, which led to four percent fewer deaths – that is, for every hundred women there were four fewer deaths. That is a lot.

Why is radiation is necessary after the cancerous lump is removed? Look at the origin of the word, perhaps from Hippocrates, to whom breast cancer resembled a crab, which in Greek is cancer. Think of a crab with a central core body and legs sticking out from this center. Well, the surgeon will remove the body of the breast cancer but will the surgeon remove all the legs? Maybe not. That is why radiation is important. We think that if it did come back, we could catch it in time, but maybe not.

So get your radiation. No excuses

Colonoscopy isn’t perfect.

I think of this when I see our friend Sarah. About five years ago her husband died of colon cancer even though he had a “negative” colonoscopy two years before. Everyone blamed the poor doc who did the procedure, but it turns out that he might not have been at fault. Colonoscopy reduces the chance of dying from this cancer, but doesn’t entirely eliminate it.

I was reminded of this by a recent report in the Journal of Clinical Oncology. The study, done in Germany, found that the chances of developing colon cancer within ten years of a negative colonoscopy were about one-fourth to one-third that of people who didn’t have the procedure. That is good, but not great.

Another study, this time from Canada, (Annals of Internal Medicine, January, 2009) came up with similar results. Only this study looked at the risk of dying from colorectal cancer after having a negative colonoscopy, like my friend Sarah’s husband. Their numbers were similar to the German group. The risk of dying from colorectal cancer, if you had a negative colonoscopy, was one-third that of people who never had a colonoscopy. Still good, but not great. And, if by any chance, the cancer started in the right side of the colon, the part of the colon farthest from the rectum, colonoscopy did not lower the chance of dying from colorectal cancer. People with cancers developing in the right side of the colon were not helped. This was the case with Sarah’s husband.

This is confusing, but let me explain. The colon is a fairly long tube that runs up the left side of the abdominal cavity and then crosses over to the right side. Cancers that develop on the left side are easy to spot. The colonoscopy tube has no problem getting there and the cancers generally start as polyps, which stand up and are easy to spot. But cancers on the right side are a problem. They are hard to find because they tend to be flat and not stand up like polyps. Also, it is hard to get that part of the colon really clean so that the colonoscopist can see everything that is there. And finally, snaking the colonoscope up that far is challenging.

Whatever the reason, the doctor who examined Sarah’s husband’s colon may have done a good job. But, since the tumor was on the right side, the odds were stacked against him. The procedure isn’t that good for cancers on the right side of the colon and perhaps gives people a false sense of security so when they have symptoms they ignore them.

This doesn’t help Sarah, but at least her husband’s death was not due to negligence, but rather to bad luck. His cancer started on the wrong side.

You are never too old for chemotherapy

One of the mysteries of my practice was that I could never predict how well or poorly a patient would tolerate chemotherapy. My bias was that the older a patient was, the less well he or she would be able to take the stuff. Not true. Often my oldest patients would float right through their treatment while younger ones suffered major side effects. I couldn’t explain it except perhaps that having lived a long life exposed these older folk to adversity, which made them better able to tolerate their treatment.

But, there was little written information that confirmed my experience. Most studies of chemotherapy excluded older patients, even though over half of all people with cancer are over 65. But now studies of the elderly are being done. Recently two reports have appeared that focused specifically on cancer in older folks.

The first report, published in the May 21 issue of the British journal, The Lancet, looked at chemotherapy for widespread colorectal cancer in patients in their 70’s. The investigators tested different regimens in these people to see if there was much of a difference in their tolerability and benefit. Doses were given at 80 percent of recommended and then the treating oncologist could lower or raise the dose as he or she saw fit. Rarely did the doctor raise the dose and about half the time it was lowered or even stopped. Yet, the treatment proved beneficial. Over half the patients reported that they felt better. This usually means that the cancer has regressed some and that the side effects of the treatment were tolerable. The one negative part of the report was that these patients did not live as long as younger patients given the same treatment. But, this may be just that cancer is more destructive in the elderly.

A second report, also in The Lancet (Sept. 17) examined whether older patients could tolerate and benefit from standard two drug chemotherapy for lung cancer. These patients were really old, ranging from 70 to 88 years. Half the patients received only a single drug, vinorelbine, which has few side effects and can be effective in lung cancer. Yet it is much more effective when combined with the second drug, carboplatin. This was given along with the vinorelbine to the rest of the patients. Both groups tolerated the drugs and were helped. But, the second group of patients, who received both drugs lived longer with hardly any more side effects than the patients who were given only the one drug, vinorelbine.

None of this means that elderly patients can be given highly aggressive and toxic chemotherapy, although we actually don’t know this for sure because there are no studies. But it does mean for certain that they can receive the benefits of some chemotherapy. You just can’t count us old folks out.