There have been great breakthroughs in cancer research over the past several months. Elizabeth Farnsworth sorts through the news on cancer with a panel of oncologists.
ELIZABETH FARNSWORTH: For several months running newspaper headlines have trumpeted good news from the cancer research front. In March, a new report showed that after almost 20 years of rising cancer incidence and death rates, both declined between 1990 and 1995. Then in early April researchers at the National Cancer Institute said they found the drug Tamoxifen so promising in preventing cancer in high-risk women that clinical trials were interrupted so the patients on placebos could be given Tamoxifen instead.
DR. BERNARD FISHER, National Cancer Institute: This is the first time in history we have evidence that breast cancer can not only be treated but also prevented.
ELIZABETH FARNSWORTH: The research also showed that Tamoxifen can have serious side effects, including an increased risk of uterine cancer for women who take the drug. This month cancer doctors and researchers meeting in Los Angeles reported that a related drug, Raloxifene, works like Tamoxifen but without the side effects. Raloxifene is already on the market under the name Evista as a substitute for estrogen replacement drugs, which help menopausal women stave off osteoporosis. In one study of almost 8,000 women Raloxifene reduced the incidence of breast cancer in post-menopausal women by 66 percent. And there was more good news at the same Los Angeles gathering of oncologists. A new drug, Herceptin, added to chemotherapy in a test on patients with a fast-growing, usually fatal form of breast cancer, caused tumors to shrink substantially in 53 percent more women than those on chemotherapy alone. Researchers in Los Angeles also described tests showing that Taxol, a drug already in use for ovarian and advanced breast cancer, can reduce the recurrence and death rate of patients with early-stage breast cancer.
DR. ALLEN LICHTER, American Society of Clinical Oncology: People will look back at 1998 as the year that was the beginning of the end of breast cancer.
ELIZABETH FARNSWORTH: Also in Los Angeles Canadian researcher reported evidence that routine screening of men for prostate cancer can substantially reduce deaths from the disease, saving thousands of lives each year. Earlier this month, in perhaps the most dramatic headlines, newspapers across the country drew attention to a tantalizing study first released last November. Two experimental drugs: Endostatin and Angiostatin, cured cancer in mice by cutting off the blood supply to tumors, thus stemming their growth and in some cases eliminating the tumors altogether. But the drugs haven't been tested in humans yet.
DR. JAMES PLUDA, National Cancer Institute: It looks very promising in mice, but, as you know, a lot of things that have looked promising in mice, so far, have not shown to be of equal use in people.
ELIZABETH FARNSWORTH: A similar drug that has been tested in a very limited way on people is showing what researchers call modest results.
ELIZABETH FARNSWORTH: Despite the apparent research breakthroughs, some grim statistics also persist. More than 1.2 million Americans will be diagnosed with cancer this year, and more than ½ million will die from it. Though mortality rates have improved in some cancers, they are worse for lung and prostate cancer. And only 4 percent of those diagnosed with pancreatic and 21 percent of those with stomach cancer will live past five years. Here now to help assess the war against cancer are three oncologists: Dr. Lynn Schucter, director of the clinical research unit at the University of Pennsylvania Cancer Center; Dr. Derek Raghavan, chief of medical oncology and associate director for clinical research at the Norris Cancer Center at the University of Southern California; and Dr. Leonard Zwelling, associate vice president for clinical research at the University of Texas and the Anderson Cancer Center. Thank you all very much for being with us. Dr. Schucter, beginning with you, do you agree with the doctor in the piece who said that 1998 may be the year that was the beginning of the end for breast cancer?
DR. LYNN SCHUCTER, University of Pennsylvania Cancer Center: Well, I think that this meeting-the ASCO meeting in Los Angeles-certainly presented data on a lot of very interesting studies for women with breast cancer from the entire spectrum, that is, the prevention of the disease in women at risk for it, then looking at women who were at high risk for the development of recurrence of their breast cancer, and then finally advances in the treatment for women who had metastic disease or breast cancer that had gone beyond their breast. Whether this is the end of breast cancer, I think that's premature. I wish that were the case, but I think we're excited about these new approaches to the treatment and better ways of using therapy. We still don't have a definite cure for breast cancer once it's traveled beyond the breast and the lymph nodes, but very exciting results.
ELIZABETH FARNSWORTH: And, Dr. Schucter, I read that doctors' telephone lines just kept ringing and ringing and ringing. Were these results hyped too much, giving people too much hope?
DR. LYNN SCHUCTER: Well, I think the breast cancer stories were actually presented with good perspective. I think the latter story you touched on-the Angiostatin and Endostatin-really is what got patients and their families very excited about a new approach and then were very disappointed to learn that that drug is at least a year away from entering patients for clinical trials.
ELIZABETH FARNSWORTH: So, Dr. Raghavan, if a person with breast cancer comes into an office now, are their chances better because of these drugs, or are the chances still about the same, and it will be more time before their chances of survival improve?
DR. DEREK RAGHAVAN, USC/Norris Cancer Center: Well, I think the chances are improving. You know, I think one of the difficulties is that in the biomedical research environment we present information as it becomes available. And sometimes there is a level of hype that disconnects the reality of what we're seeing. And I think that patients do have a better outlook today than perhaps they had fifteen or twenty years ago. And I think that's largely because there has been a coming together of a number of different forces. I think our molecular biologists really have got a very nice handle on some of the factors that control the growth and division of cancer cells. We're certainly getting a much clearer understanding of why cancer cells may be resistant to some types of treatment. If you bracket that with the availability of newly-synthesized drugs, a new approach at the Federal Drug Administration that is fast-tracking new drugs that really look promising and that are likely to help patients, I think in that situation, those forces come together to make the outlook very promising. I think Lynn Schucter is absolutely correct, but if we hype these sort of advances too much, then some patients will become disappointed. But I think that it's an optimistic time, certainly the most optimistic that I felt in the last 15 years.
ELIZABETH FARNSWORTH: So, Dr. Zwelling, some of the drugs we hear a lot about but that we only hear about for breast cancer, does the science behind those drugs, is that science applicable to drugs that may eventually be useful for other cancers?
DR. LEONARD ZWELLING, University of Texas M.D. Anderson Cancer Center: Yes. I think as we learn more and more about what makes a cancer cell different from a normal cell, that will give us more handles on how to develop therapies like Herceptin or like the Anti-Angigensis drugs that might be specific for specific kinds of cancers. So I think the principles are there, it's really the reward for the 27-year investment in the war on cancer we've made since 1971. Now the molecular biology and the proteins made by the aberrant genes in cancer really are coming to fruition in therapies for patients.
ELIZABETH FARNSWORTH: All right. Dr. Raghavan, I want to begin now with you on lung cancer and go through various kinds of cancer to see what's happened in those fields. Let's start with lung cancer. Lung cancer is still a very difficult cancer. It claims about 160,000 lives a year. Are new prevention or treatment methods making a difference in lung cancer?
DR. DEREK RAGHAVAN: Well, I think they are. If I could control the health care budget and was given one option to reduce the cancer in the nation and in the world, I would do just one thing, and that is, I would stop people smoking. It's a hackneyed, boring phrase, but the reality is that we know that lung cancer, throat cancer, stomach cancer, bladder cancer, and so on are all directly attributable to smoking. The good news is that men have finally gotten sensible. The new smokers, who are men, the rate of those new smokers is going down. And as a consequence, the number of new cases is actually plateauing in men. The flip side, unfortunately, is that the generation of now women, who are emancipated, have started to smoke more than ever, and that's really very disappointing. And, as a consequence, we are seeing almost an epidemic of lung cancer in younger women, which is really tragic. But I think we know what to do about lung cancer. We stop people smoking, and the numbers will go down dramatically. I think the other things that are happening that are very exciting is there are a collection of new anti-cancer agents that have been developed for a number of different purposes, which in the last twelve to eighteen months we've discovered to be really very powerful weapons against advanced lung cancer. And then perhaps one of the most exciting developments over the last three or four years has been the discovery that certain types of lung cancer that heretofore we thought were inoperable and to some extent untreatable and now potentially curable if you shrink them initially with chemotherapy and the either operate or use radiation treatment. Finally, there's been one other development, which has been a very nice demonstration that giving radiotherapy in a new way were you do two doses a day, instead of just one, will improve the level of control of cancers where they arise. So there are a number of different things happening that are actually improving the outlook for patients, but I would still say if I had one therapeutic modality, it would be to ban smoking.
ELIZABETH FARNSWORTH: And Dr. Schucter, colon, rectal cancer is expected to claim about 57,000 lives this year, but the five-year survival rate has improved. Why? What are the new developments here?
DR. LYNN SCHUCTER: Well, one is an understanding of who should be treated with chemotherapy after they're diagnosed with colon cancer. So, for example, someone presents with colon cancer, has their surgery, there's no evidence of spread beyond their lymph nodes, but we understand now that they would benefit from additional chemotherapy. And a recent paper showed that now patients can receive just six months of chemotherapy instead of twelve months of chemotherapy. And we see an improvement in disease-free survival and how long patients live. For 20 years now we've only had really one drug effective against colon cancer and that was something called 5FU. And there is a new drug called CPT11-that's CPT11-and that also shows very impressive responses in patients with colon cancer that have gone beyond the colon and may have metastasized to liver or other sites. So there are now advances in the treatment of colon cancer, a disease that has been thought to be very resistant to chemotherapy.
ELIZABETH FARNSWORTH: And Dr. Zwelling, before I move on to prostate cancer, let's bring in Angiostatin and Endostatin here, these drugs that in mice cut the supply of blood off to tumors. People who have really difficult cancers are looking to this with a lot of hope. How far are we away from these kinds of drugs maybe helping people?
DR. LEONARD ZWELLING: I think Dr. Schucter mentioned we're probably at least 12 months away from the initial clinical trials, which will really decide how to use the drugs, and eventually they will probably be combined with more conventional forms of therapy, that is, radiotherapy, chemotherapy, and surgery. There are drugs now that are being tested in people that work on the same principle-that is, they try to starve out tumors. And as you mentioned in your opening piece, they have had-they've shown modest effects so far, but they're still in early trials, so it's hard to know. I think the principle of using anti-Angigenesis agents-in other words, directing therapy against the environment that the tumor establishes-instead of against the tumor, itself-is really a new idea. It's an idea that came forth through this tremendous amount of research that has gone on over 30 years. And my guess is it will find a home in different kinds of cancer. We just don't know yet. We just have to do the trials and find out.
ELIZABETH FARNSWORTH: And Dr. Raghavan, we heard in the piece about the importance of screening for prostate cancer. Do you agree with that? I know that was controversial. And what else is happening in prostate cancer research?
DR. DEREK RAGHAVAN: Well, you're right. This study to which you alluded is actually very controversial. And I think that probably PSA screening is not really fully ready for prime time, but the study that you mentioned was one done in Canada, in which some investigators looked at people who were not known to be patients. They took their names from the electoral rolls-men aged 45 to 80-and divided them up into groups that might be screened with physical examination and a blood test. The blood test was measuring a substance called prostate specific antigen. It's a little protein that's released by normal prostatic tissue in some people and from cancerous tissue. I think the problem is that it was a tremendously exciting study when it was designed about 10 years ago, but as the data were presented at the annual scientific meeting of the American Society of Clinical Oncology, we heard a study that I personally believe was mis-analyzed, and where the investigators, while doing a very good study, when they looked at the results, made some fundamental errors in design. I think the reality is that a meeting such as this, where seventeen/eighteen thousand cancer specialists will get together, which really functions as sort of an international clearinghouse of information, you'll get information that some experts just don't buy. And so in this situation, I think that the use of PSA screening for people without symptoms is probably unproven at the present time. There are two big international trials that are ongoing that may give us the answer as to whether this will ultimately save lives.
ELIZABETH FARNSWORTH: And, just briefly, are there other developments?
DR. DEREK RAGHAVAN: Yes. There are some very exciting developments. We've discovered that locally advanced prostate cancer-that's cancer that has spread locally and that normally would be viewed as very difficult to treat-you can actually cure a larger number of patients by shrinking the cancer down with a type of hormonal therapy--prostate cancer, in fact, responds to hormonal treatments--and then once the gland has shrunk down, using radiation or surgery to remove it completely. That's one thing that's a major advance. Another very exciting presentation came from a group who started to use gene therapy, that is, the insertion of genetic materials into cancer cells to try to control locally-recurrent prostate cancers. While this has mostly been done in experimental animals, there are some preliminary human studies that suggest that this technique might work, and it should spawn a whole series of innovations in this type of therapy. So I think there are some real steps forward. I'm just not personally convinced that PSA screening for people with no symptoms is likely to be helpful. I do think, however, that we need to know that prostate cancer will run in some families, that black Americans, unfortunately, are very much at risk at risk of this disease, and that people should be aware of the symptoms of prostate cancer and have those checked out very rigorously.
ELIZABETH FARNSWORTH: And Dr. Schucter, turning to the cancers with the very worst survival rates-pancreatic cancer, for example, stomach cancer-any new developments in these?
DR. LYNN SCHUCTER: There are new medications, new chemotherapy drugs. A medication called Gemsidavine was approved by the FDA in the last 18 months. And that's the first time we've seen a drug that actually can help patients decrease their symptoms associated with pancreatic cancer. So these are tougher cancers to treat, but there are many new approaches that are being done to investigate these more difficult cancers.
ELIZABETH FARNSWORTH: And Dr. Schucter, recognizing that there have been so many disappointments in the past with big announcements about cancer drugs and then great disappointments afterwards, you said earlier that you really are beginning to have more hope now. Do you feel like some fundamental corner has been turned?
DR. LYNN SCHUCTER: Absolutely. I think that what's different today is that we have a better appreciation for what's wrong in a cancer cell, and knowing what's wrong, or what's broken in a cancer cell, allows us to develop more specific therapies to fix it. So, as the doctor from M.D. Anderson suggested, we have invested a huge amount in this country to understanding basic cancer, what is wrong with the cancer cell. And as a result of that investment, we understand how to approach the problem. And that was very exciting. That's what the enthusiasm is all about, developing specific therapies that target what's wrong. The other hope is that these newer approaches will spare patients the side effects associated with chemotherapy. So if you're much more specific about what's broken, the hope is that you're going to spare the normal cells, and patients won't experience the nausea, vomiting, hair loss, other things that we see with chemotherapy.
ELIZABETH FARNSWORTH: And Dr. Zwelling, there's actually far more testing going on right now, right, on far more drugs, is that true?
DR. LEONARD ZWELLING: Oh, sure, we have almost 500 trials in any given year that are accruing patients here at M.D. Anderson. One of them, by the way, is a gene therapy trial among cancer, which has already demonstrated activity, real activity that Jack Roth did. I think the real hope is that because of the investment in basic research we understand three important things about cancer that have changed: One, cancer is clearly a disease of genes, so the gene therapies are worth trying; two, those genes code for specific proteins, with specific biochemical pathways that in themselves can be targeted by specific drugs; and three, cancers change as the environment in which they live, and we can attack the environment or the aberrant environment caused by cancer. And that's what the anti-angigenesis drugs are all about. So we have more handles on how to attack cancer. And the last important point to remember is that cancer is not one disease. It's many diseases. And, in fact, breast cancer, itself, is many diseases. And the hope eventually is to use this genetic information to individualize cancer therapy for different patients, so even though two women may have what appears to be similar breast cancer, a molecular analysis of their breast cancer may show differences that we can exploit with very specific therapies, and, as Dr. Schucter said, with very low toxicity.
ELIZABETH FARNSWORTH: Okay. Well, thank you all very much for being with us.
DR. LEONARD ZWELLING: Thank you.
DR. LYNN SCHUCTER: Thank you.