Cary

Sorry about the confusion, something must have happened to my profile between my last post in Feb 2005 and now. My Father passed away in Nov. 2004 from sepsis. Everything was going fine cancer wise for the most part though, just some low dose treatments to keep everything small/gone. I can't seem to update my email address in my profile, does anyone have a trick on how to get it to work?

another 6 months and you could have just retired Congrats!! I knew you would make it!!

I don't know if it's right or not, but a lot of places are actually selling custom braclets/wristbands. http://froogle.google.com/froogle?q=cus ... +bracelets Cary

Everyone, I just wanted to thank all of you for your kind and heartfelt responses, I'm sorry I haven't been able to post sooner, but it's been pretty hectic around here, the relatives have already started arriving and will be here for the next couple of weeks(my dads funeral is on Thursday). I also have limited access to the internet for a few more weeks, but I will try and keep all of you updated. Thank you, Cary

Kitty, Is you father experiencing mini-strokes or mini-seizures? My dad was having mini-seizures and declined in health over a couple of weeks. He eventually had a full seizure and became completely paralyzed (for 2 days) before they found his brain tumors back in 2003. He received WBR for his 21 brain mets(1cm-2cm each) and currently has no evidence of disease. You may want to get a second opinion. Cary

Geoff, That is great news, if you would like first hand knowledge on the vaccine therapy, i know a lady that flies to Germany, to get treatments from Dr. Nesslehut. She has mentioned in the past, that she would be willing to correspond with others that have questions. I believe her secondary Oncologist is Dr. Chang also. Cary

Marisa, Sounds interesting. I think Karel and his daughters are from Australia, I wonder if they have heard/looked into this treatment and what they think of it. Cary

Karel, I believe it's from the Journal of Endocrinology (June 2004). I am not sure if the full version is available on-line. I was actually emailed the "accepted preprint" months ago, then received the published version the same way. Cary

I know i must have posted this article before, but i can't seem to find it. When my dad was doing WBR we cut out most of his supplements and just happened to leave his salmon oil and his homemade vegetable drink along with his other "off label" cancer treatments. Hopefully this combination made the difference, since he has very little if any permanent damage. Anticancer Res. 1999 Nov-Dec;19(6C):5583-6. (Abstract) Increased survival in brain metastatic patients treated with stereotactic radiotherapy, omega three fatty acids and bioflavonoids Gramaglia A, Loi GF, Mongioj V, Baronzio GF National Cancer Institute, Milan, Italy. Stereotactic radiotherapy represents a method to effectively treat brain metastases with high precision and with high doses. Few acute toxicities are associated with stereotactic radiotherapy, however delayed reactions may occur and after six months, 20% of patients can develop radionecrosis. To avoid this adverse effect, in patients with metastases localized in critical brain areas, a supplementation of Omega three fatty acids and bioflavonoids has been used. At the end of 1997, we initiated a series of retrospective studies to test the efficacy of stereotactic radiotherapy on 405 patients, and the prognostic importance on survival of various variables among which this type of supplementation. From the comparison of various survival curves with the Cox multivariate analysis, it emerged that the patients using this supplementation had a decreased risk ratio and an improvement in survival time. A decreased number of radionecrosis was noted. We suggest their use as radioprotectors. PMID: 10697622 [PubMed - indexed for MEDLINE] Source: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

MJ, Yes you can, I will have to pull some of my old research and post/repost. Radiation is actually more effective/less side effects while on TM(low copper levels). Cary

Alisa, thanks for the link, i will check it out. I bought IP6 a couple of days ago from the place Karel mentioned. I am headed over to vitaminshoppe.com to compare prices. Cat: it's been mailed. Cary

Cat, My father has been on Tetrathiomolybdate since February 03. I don't think there are any clinical trials currently being conducted, but it has been available "off-label" since basically the first clinical trial data was published. It a pretty simple therapy. I do have the latest research paper that was published, but unfortunately it's in PDF format. If anyone wants the paper though, i will email it as an attachment. I have posted all the older articles on Tetrathiomolybdate so you should be able to do a search for "copper" on this board. Alisa: I went to nutricology a few days ago, looking for IP-6 and i can't seem to find it on their list of products, do you have a direct link to the IP6 page. Cary

Hi Geoff, Dendritic cell vaccines are currently available in Germany. The info below is from a lady that is currently flying to Germany to receive treatments. I find it interesting that the German and U.S. researchers are in such close contact(I think that is good news). If you have any questions let me know. They are contemplating a new 'joint' web site with some U.S. doctor(s) that may help some of you who have so many questions and may also lay out more clearly all the expenses involved in the treatment, the odds of success, the experiences in your own kind of cancer, etc. But this is in the future. They are always comparing and working with other dendritic cell research groups throughout Europe, and are in contact with the U.S. groups as well. Because of the difference in philosophical approach between the German "E Commission" and the U.S. FDA, they are legally able to treat patients (for whom there is no current curative treatment) in other than a clinical trial setting. The advantage here is two fold: the patient does not need to fit a rigidly defined protocol to qualify for a specific trial AND because there is no rigid protocol, they can tailor the fine details of each treatment to each individual based on their experience with that patient's kind of cancer and disease stage. In most cases, one can continue with one's other treatments including most alternative and complementary treatments -- but of course one must first check with them to be sure there is no problem in doing so. They, in fact, highly recommend that their patients take certain supplements/vitamins etc. to strengthen the immune systems and/or increase the effect of the dendritic cell vaccine. Unlike many dendritic cell treatments, they can treat patients who do NOT have fresh tumor tissue although, in many (most?) cases they like to have fresh tumor tissue to use in combination with the patient's own blood. But for patients like me, who have not been able to get fresh samples of the metastatic lesions, this ability to work even without tumor lysates is a plus.

The Journal of Clinical Investigation is pleased to announce FREE ACCESS to its electronic archive from 1924 through 2004. Full PDF versions of all articles are now available through PubMed Central. View the archive at: http://www.pubmedcentral.com/tocrender. ... ournal=120 The JCI is the ONLY high-impact journal that provides FREE ACCESS to all its articles from the day of publication. The JCI was the first top-tier journal to successfully launch free access in 1996, and we remain committed to free-access publication. Sincerely, Ushma Savla, Ph.D. Executive Editor, The Journal of Clinical Investigation 2003 Impact Factor: 14.307 View the current issue at: http://www.jci.org

Sounds promising. Cary http://carcin.oupjournals.org/cgi/conte ... t/bgh232v1 Abstract A significant anti-cancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP6) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP6 reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP6 on both. IP6 inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC50 = 0.74 mM). The combination of IP6 and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP6 inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP6 significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (p < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP6 for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP6 treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (p = 0.012). Thus, IP6 has an inhibitory effect on induced angiogenesis."

http://www.jco.org/cgi/content/abstract/22/14/2800 Allogeneic Vaccination With a B7.1 HLA-A Gene-Modified Adenocarcinoma Cell Line in Patients With Advanced Non–Small-Cell Lung Cancer Luis E. Raez, Peter A. Cassileth, James J. Schlesselman, Kasi Sridhar, Swaminathan Padmanabhan, Eva Z. Fisher, Paulette A. Baldie, Eckhard R. Podack From the Division of Hematology/Oncology, Department of Medicine, Department of Microbiology and Immunology, and Department of Epidemiology and Public Health, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL Address reprint requests to Luis E. Raez, MD, FACP, Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, 1475 NW 12 Ave # 3510, Miami, FL 33136; e-mail: lraez@med.miami.edu PURPOSE: To determine the safety, immunogenicity, and clinical response to an allogeneic tumor vaccine for non–small-cell lung cancer, we conducted a phase I trial in patients with advanced metastatic disease. PATIENTS AND METHODS: We treated 19 patients with a vaccine based on an adenocarcinoma line (AD100) transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated intradermally with 5 x 107 cells once every 2 weeks. Three vaccinations represented one course of treatment. If patients had complete response, partial response, or stable disease, they continued with the vaccinations for up to three courses (nine vaccinations). Immune response was assessed by a change between pre-study and postvaccination enzyme-linked immunospot frequency of purified CD8 T-cells secreting interferon-gamma in response to in vitro challenge with AD100. RESULTS: Four patients experienced serious adverse events that were unrelated to vaccine. Another four patients experienced only minimal skin erythema. All but one patient had a measurable CD8 response after three immunizations. The immune response of six surviving, clinically responding patients shows that CD8 titers continue to be elevated up to 150 weeks, even after cessation of vaccination. Overall, one patient had a partial response, and five had stable disease. Median survival for all patients is 18 months (90% CI, 7 to 23 months), with corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and 30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not bear a significant relation to response. CONCLUSION: Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination. Supported by the Research Career Development Award given by the American Society of Clinical Oncology, University of Miami/WCA, RO1-CA39201-14, and the family of Iris Zeitler. Preliminary results were presented at the 92nd Annual Meeting of the American Association of Cancer Research (AACR), San Francisco, CA, April 6–10, 2002, and the 10th World Conference on Lung Cancer, Vancouver, Canada, August 10–14, 2003. In memory of Dr Kasi Sridhar (1953–2001).

http://seattletimes.nwsource.com/html/h ... ree30.html Cigarette stand-ins: a safer addiction? By Valerie Reitman Los Angeles Times A growing number of anti-smoking researchers and public-health advocates are adopting a tack that not long ago would have been considered heresy: suggesting that hard-core smokers who can't kick the habit would be better off switching to new smokeless tobacco products. With slogans such as "Spit-free" and "For when you can't smoke," these products differ markedly from the messy snuff and chewing-tobacco stereotypes associated with your granddaddy's spittoon or certain pro baseball players' stuffed cheeks. They are clean, discreet, last about 30 minutes and come in mint, wintergreen and other flavors. Some go down easily, dissolving much like a breath mint, while others look like tiny tobacco-filled teabags, tucked into the side of the mouth and discarded like chewing gum. Though no one is calling the products "safe" — any tobacco that has been cured contains some carcinogens — numerous epidemiological studies have shown that smokeless tobacco is far less likely to cause any type of cancer, including oral cancer, than cigarettes. "If someone can't quit smoking, there is no question that smokeless is much safer. It doesn't cause heart or lung disease, and if it does cause cancer, it does so at a much lower rate," said Dr. Neal Benowitz, a professor of medicine at University of California, San Francisco, and director of its cancer center's Tobacco Control Program. Gary Giovino, director of the Tobacco Control Research Program at the Roswell Park Cancer Institute in Buffalo, N.Y., agreed. "If everybody who smoked used these instead, there would be less disease." Many Americans may be unaware that most scientists and researchers say that smokeless tobacco is less hazardous than cigarettes in causing deadly disease. That's not surprising. For years, some private and government medical organizations have disseminated outdated information on the subject. For instance, the Mayo Clinic in Rochester, Minn., recently acknowledged that information on its Web site was incorrect and would be revised. Though some information on the Centers for Disease Control and Prevention's Web site was modified after one prominent researcher protested it, the agency, part of the U.S. Department of Health and Human Services, takes the position that "there is no safe form of tobacco" and that there "is no significant evidence that suggests that smokeless is a safer alternative to smoking," spokeswoman Karen Hunter said. Some tobacco researchers contend the misinformation hinders individuals from making educated decisions about whether to switch to smokeless products. "I think it's not scientific and is a deception," said Lynn Kozlowski, who heads Pennsylvania State University's biobehavioral health department. "What the studies show is that in the U.S., smokeless causes oral cancer but that cigarettes are even more likely to cause oral cancer." With names that include Ariva and Stonewall, both made by Star Scientific Inc., and Revel, made by the U.S. Smokeless Tobacco Co., which also makes the Copenhagen and Skoal brands, the new products have been rolled out in a few U.S. cities and are also available from their manufacturers' Web sites. They promise to deliver the nicotine fix smokers crave and take the edge off the physiological urge to light up. Smoke worse than nicotine Although the nicotine in cigarettes is powerfully addictive, it is the cigarette smoke — not the nicotine — that delivers the killer punch, possibly producing as many as 60 known carcinogens and about 5,000 other chemicals. Studies show that many people still believe that it is the nicotine that is the harmful element. Brad Rodu, an oral pathologist at the University of Alabama, said nicotine should be treated more like caffeine: as an addictive drug that can be used safely. (His "tobacco harm-reduction" research is funded by a five-year grant from U.S. Smokeless.) "We would have smokers understand the nicotine addiction can be separated from the smoking." Many public-health advocates fear that providing smokers with alternative products will keep them from quitting altogether, the healthiest option. They also fear that some nonsmokers might start using them and, if they do, that the nicotine will encourage them to start smoking. Some of this concern stems from the difficulty in knowing the long-term hazards of substitute products as well as the distrust of the tobacco companies based on past claims. For example, in 1981, the U.S. Surgeon General recommended that smokers who couldn't quit would be better off switching to "low-tar" or "light" cigarettes because they were less likely to develop smoking-related illnesses. Instead, smokers were found to puff harder and inhale more deeply to compensate, thus taking in an equal amount of tar or more. Internal documents revealed that the cigarette makers knew that to be the case all along. Kenneth Warner, director of the University of Michigan Tobacco Research Network, said he was convinced that the promise of reduced risk kept tens of thousands smoking rather than quitting — undoubtedly hastening many deaths. Nearly three years ago, the National Cancer Institute charged that light cigarettes did nothing to lower smokers' health risks. Worries about teenagers Among the largest fears is that teenagers will get hooked on smokeless products, then switch to smoking when they realize that cigarettes deliver a faster and more powerful hit of nicotine. Greg Connolly, former director of the Massachusetts Tobacco Control Program, said kids who start on smokeless tobacco were three times more likely to go on to smoking cigarettes — and that some smokeless companies had deliberately targeted teenagers. He agreed that the newer products are less carcinogenic and probably safer to use but said the new products were not being aggressively pushed by their makers. Instead, the more carcinogenic, dirtier discount brands of smokeless products are growing in popularity. "I'd be the first to say the new products are safer," Connolly said. "But I don't want them to be hurting our kids. This is an industry you can't trust." The push for safer alternatives comes amid mounting gloom about smoking. Although cigarette smoking has declined dramatically from its peak in the 1960s, it has leveled off in the past decade. About 46 million Americans — 22 percent of adults, according to the CDC — still light up each day despite aggressive public-education campaigns, heavy cigarette taxes to make them less affordable, significant social stigma and widespread smoking bans in public places. An estimated 10 million Americans use smokeless tobacco. It's a very tough habit to break — tobacco researcher and former smoker Giovino calls quitting "a toothache in the soul." Although 70 percent of smokers say they want to quit and 34 percent of them attempt to do so each year, only 10 percent manage to stay smoke-free for a year, according to the Institute of Medicine. "We are not promoting tobacco use," the University of Alabama's Rodu said. "But we have a reality of 46 million smokers, and they now have only one option: to quit. It's quit or die."

http://www.healthtalk.ca/mint_cancer_07052004_4930.php Mint Leaf May Destroy Cancer July 05, 2004 Researchers say they have discovered a chemical in a Chinese mint leaf that destroys cancer cells. Professor Alan McGown of Salford University near Manchester, England, extracted a chemical from the Chinese herb that he says blocks the blood supply to tumors, thus destroying the cancer cell's ability to grow. The only testing of the chemical so far has been in a laboratory, McGown hopes to change that. If funding can be secured, Professor McGown hopes to conduct live and human trials within the next three years. Doctors in China have been using the mint herb (scutellaria barbata) for hundreds of years to fight disease. It belongs to a group of herbs named the Scutellaria species or scullcap. Both the root and the above-ground part have been used to make herbal medicines. The root has been used in traditional Chinese medicine to treat lung cancer and other medical problems.

http://tinyurl.com/yrjxg July 9, 2004 p39 Avastin, Tarceva combination yields initial promising results for cancers. 2004 JUL 9 -- Genentech, Inc., (DNA) and OSI Pharmaceuticals (OSIP) announced results from phase I/II clinical studies examining the combination of Avastin (bevacizumab) and the investigational small molecule Tarceva (erlotinib HCl) in the treatment of metastatic renal cell carcinoma (kidney cancer) and relapsed non-small cell lung cancer (NSCLC). These trials are important because patients received no chemotherapy and instead were treated with a combination of two therapies targeted at two distinct avenues of growth in cancer: angiogenesis and EGFR signaling. The results were presented at the 40th Annual Meeting of the American Society of Clinical Oncology (ASCO). Avastin is a therapeutic antibody designed to inhibit angiogenesis, the process by which new blood vessels develop, which is necessary to support tumor growth and metastasis. Avastin is currently approved in the United States for use in combination with intravenous 5-Fluorouracil (5-FU)-based chemotherapy as a treatment for first-line metastatic colorectal cancer. Tarceva, an investigational therapy, is an oral, once-a-day, small molecule designed to target the human epidermal growth factor receptor 1 (HER1/EGFR) pathway, which is one of the factors critical to cell growth in many cancers. "As cancer patients lives longer, quality of life and avoiding toxic side effects become more important," said Gwen Fyfe, MD, Genentech's vice president, Clinical Hematology/Oncology. "Evaluating the combination of Avastin and Tarceva in certain cancers is representative of our strategy to inhibit tumor growth by simultaneously targeting different cancer pathways. We are encouraged by the response and progression-free survival data observed in these studies of patients with advanced kidney and lung cancers and believe these data support future evaluation of this combination in multiple tumor types," Fyfe said. In addition to the combination studies in recurrent NSCLC and metastatic kidney cancer, preliminary data from studies evaluating the combination of Avastin plus Tarceva in metastatic breast cancer and recurrent and/or metastatic head and neck cancer will be presented at this year's ASCO meeting. This single-arm phase II study, presented by John Hainsworth, MD, of the Sarah Cannon Cancer Center in Nashville, Tennessee, focused on preliminary results from 62 patients with metastatic renal cell carcinoma (kidney cancer) treated with a combination of Avastin and the investigational drug Tarceva. At the time of analysis, 62 patients had been enrolled in the study and 58 were evaluable for response. The authors reported that at 8 weeks, 21% of patients (12/58) experienced an objective response (defined as a 50% or greater decrease in the size of a tumor) to the combined therapy and 66% (38/58) experienced a minor response or disease stabilization. At 6 months, 67% of the evaluable patients (39/58) had progression-free survival and after 1 year, 50% of patients (29/58) had progression-free survival. Overall survival after 6 months was 92% and after 1 year was 81%. The Grade 3 or 4 adverse events observed in the study included hypertension (8%, 5/58), diarrhea (10%, 6/58), rash (13%, 8/58), nausea/vomiting (10%, 6/58), bleeding (5%, 3/58), pruritus (3%, 2/58), proteinuria (3%, 2/58), neuropathy (3%, 2/58) and edema (2%, 1/58). Alan Sandler, MD, of Vanderbilt-Ingram Cancer Center, reported on results from a multicenter phase I/II study designed to evaluate the combination of Avastin and Tarceva in the treatment of recurrent non- small cell lung cancer (NSCLC) patients. To date, 40 patients have been enrolled in the trial. At the time of analysis, median survival was 12.6 months, median progression-free survival was 7 months and the estimated 1-year survival was 54%. Partial responses were observed in 20% of patients (8/40) and an additional 65% of patients (26/40) achieved stable disease in the study. The most frequent adverse events reported were mild-to- moderate rash (93%, 37/40), diarrhea (78%, 31/40) and proteinuria (18%, 7/40). Traditionally patients with relapsed NSCLC are treated with chemotherapy, which may be very poorly tolerated by some advanced patients. If randomized, phase III trials of Avastin plus Tarceva show clinical benefit, this combination could provide an important treatment option that does not include chemotherapy.

http://washingtontimes.com/national/200 ... -5620r.htm Drug role limited in 'chemobrain,' study finds ATLANTA (AP) — Anticancer drugs might not be entirely to blame for the mild mental impairment suffered by some cancer patients undergoing chemotherapy, a study found. The findings suggest that the forgetfulness and other symptoms associated with so-called "chemobrain" might be caused by cancer itself rather than potent cancer-fighting medicines, researchers said in a study published today in the online version of the journal Cancer. In a study of 84 breast-cancer patients diagnosed with neurological problems, 35 percent reported cognitive problems before receiving chemotherapy drugs. Chemotherapy did cause a mental decline in the other patients. The study was the first of its kind to find cognitive impairment in cancer patients before they received chemotherapy. Other symptoms of the disorder include difficulty speaking or interacting socially. In the past, doctors might have assumed that all cognitive impairment found after chemotherapy stemmed from anticancer drugs because physicians never examined a patient for mental decline before treatment, said Dr. Christina Myers, professor of neuropsychology at the M.D. Anderson Cancer Center in Houston and one of the study's authors. The findings are important because some cancer patients have been hesitant to undergo chemotherapy out of fear of developing post-treatment problems, including chemobrain.

http://www.medicalnewstoday.com/medical ... ewsid=9685 Quit smoking when you are under 35 and you will live as long as someone who never smoked 20 Jun 2004 If you smoke and you are under 35 you can still expect to live as long as someone who has never smoked if you quit now, a new study reveals. Researchers said that in their studies, only the people who had given up smoking 15 years or more before they began their study had any chance of a similar life expectancy of a lifelong non-smoker. They also stressed that making a decision to take up smoking knowing that you will give up before you are 35 is wishful thinking – giving up is very hard and most people fail on the first attempt. The study was carried out at Duke University, North Carolina, USA, and was led by Dr. Taylor. The researchers said that we often overlook how badly smoking affects our quality of life while we are still alive. Most of the focus is on life expectancy. But smoking, they say, undermines you general health and quality of life while you are alive. In this study, the researchers studied the transcripts of interviews that had been carried out with middle-aged and elderly people. They talked about their health and whether they smoked or not and when they had given up. Over a period of many years these people were contacted again (on several occasions). The aim was to see how their health altered. Most people, they found, had predictable health patterns according to how they described their health at the time. The researchers calculated how long these people could expect to live and live healthily. They found that smokers lived less long than lifetime non smokers. They also found that smokers had longer periods of bad health while they were alive. Those who had given up 15 years (or more) before the start of the study lived as long as non smokers and enjoyed similar periods of good health while they were alive. Even smokers who did not complain of health problems lived less time than non smokers. It is crucial, they said, that you are not a smoker when health problems start. The longer the period of non-smoking before a health problem, the longer you are likely to live and the better your health will be while you are alive, they said. The message here, they say, is to focus on the quality of life you want while you are alive – and not just to acknowledge that smoking shortens your life. Therefore, the argument that it is better to live a short happy life than a long boring one does not stand – the smoker will most likely have a short and unhappy life in comparison to the non-smoker.

Wow, I just saw this post. Great news!! Cary

I always believed the same as Hebbie, that the patient would always receive the "best standard care" apparently I was wrong. As disheartening as this article may seem, there will always be ethical/humane researchers and institutions that will not follow this new "trend" (hopefully). Cary

I could hardly believe this article when I first read it also. I did go back and read Hebbie's recent post "Treatments boost lung cancer survival" and apparently we all missed the hints at the end of the article. “Not only did our patients live longer but I like to say they lived better,” she said, noting that patients given the drug had less cough, shortness of breath and pain than those given placebo. Erlotinib, co-developed by OSI Pharmaceuticals, Roche and Genentech, works by inhibiting an enzyme called epidermal growth factor receptor, or EGFR, that is involved in the growth of some cancers. In the study of 731 patients, those receiving erlotinib survived a median of 6.7 months, compared with 4.7 months for those on placebo. After one year, 31 percent of those in the treatment group were alive, compared with 22 percent of the other group. Cary PS: Ry, I also have great respect for the University of Michigan and Dr. George Brewer, without them my dad wouldn't be here today.

I wasn't for sure where to post this. Cary http://tinyurl.com/38bky Doctors argue over use of placebos in cancer trials By AMY DOCKSER MARCUS The Associated Press 6/8/04 9:15 AM The Wall Street Journal In a controversial shift, some of the most promising new cancer drugs are heading into clinical trials where only some patients will get the actual drug. Other patients will be given a placebo. The use of placebos is a sharp departure from past practices and is strongly opposed by some influential cancer researchers. Placebo trials generally haven't been used in life-threatening diseases such as cancer. If there is any kind of effective therapy available, the argument goes, it is unethical to give a placebo. Now, drug makers including Bayer Pharmaceuticals Corp., Pfizer Inc. and Genentech are adding placebo arms to their trials in an effort to speed promising new drugs to market. Because placebo trials make it easier to verify results, the strategy can cut down on the need for additional studies and lead to faster regulatory approval. Many in the cancer community are angry about the new approach, saying that it denies desperately ill people a last best hope. Some leading cancer centers, including the M.D. Anderson Cancer Center in Houston and the University of Michigan Cancer Center in Ann Arbor, have refused to put patients in clinical trials that use placebos. Patient-advocacy groups have met with drug makers including Pfizer and Bayer in an effort to change their minds about running trials with placebo arms. Some of the most high-profile new drugs used placebo arms in recent trials, including OSI Pharmaceuticals, Genentech and Roche Group's Tarceva for lung cancer and Bayer and Onyx Pharmaceuticals Inc.'s BAY 43-9006 for kidney cancer. A Pfizer drug being tested for gastrointestinal stromal tumor (GIST) also has run a recent trial with a placebo arm. At the American Society of Clinical Oncology meeting this weekend, researchers presented positive results from the Tarceva and BAY 43-9006 trials. The practice of using placebos in a study -- whereby some patients get the active drug, but others are given look-alike sugar pills and no treatment -- is the gold standard for drug research in many fields of medicine. The strategy makes it much easier to determine whether it is the drug, and not some other factor, that is making the difference in patients. The U.S. Food and Drug Administration, responding to patients' concerns, has developed accelerated approval processes to speed drugs to needy patients even without placebo-based trials. Richard Pazdur, director of the FDA's oncology-drug products, says "we have not insisted that trials be placebo controlled." Drug companies say that such accelerated approval still requires certain additional trials that add to what already is an estimated $800 million price tag to bring a drug to market. And the research still takes longer to accomplish. In addition to patients' meetings with Pfizer and Bayer in the past few months, other efforts are under way by patient advocates to influence trial design. A GIST patient-advocate organization, the Life Raft Group, has set up a Clinical Trials Advisory Group of cancer patients to lobby drug companies against placebo trials. In November, three major professional organizations of cancer clinicians, oncologists and researchers will meet to come up with better ways to design trials for the new therapies that are emerging. All this comes amid growing concern that it is getting harder to get patients to participate in cancer-drug studies in the first place. Just 3 percent of adult cancer patients enroll in clinical trials, according to the President's Cancer Panel report issued last week. A number of national organizations, including the National Cancer Institute, the Lance Armstrong Foundation and the National Coalition for Cancer Survivorship, all are trying to increase the percentage of adult cancer patients who enroll in trials. What all these groups have found is that one reason patients don't enroll is fear of getting a placebo, so the outcome of this current debate is sure to affect recruitment efforts. The University of Michigan Cancer Center in Ann Arbor, along with the M.D. Anderson Cancer Center in Houston, both refused to participate in Pfizer's clinical trial for GIST patients because of their concerns over the trial's placebo arm. "There is almost no good reason to ever do a placebo trial in cancer," says Laurence Baker, director of clinical research at the University of Michigan center. "The only advantage is expediency to the drug manufacturer." When OSI Pharmaceuticals ran recent Phase III clinical trials for its drug Tarceva, for advanced lung cancer, the company didn't include any U.S. sites, concluding "it would take too long to enroll patients" because of the trial's placebo arm, according to OSI Pharmaceuticals Chief Executive Colin Goddard. This meant that patients here lost early access to a potentially beneficial drug. The company reported this weekend at ASCO that the drug extended the lives of patients who took it. Mr. Goddard acknowledged that patients on placebo died more quickly than those with the drug. But that "thanks to the sacrifice of those patients, we've taken lung-cancer treatment forward," Mr. Goddard said. "Future patients will benefit." Some drug companies say they are working to come up with innovative trial designs. In the current Phase III trials for Pfizer's GIST drug, called SU-11,258, doctors are allowed to intervene if a patient's tumor grows more than 20 percent. If it turns out the patient wasn't receiving the active drug, the patient is allowed to "cross over" to the drug arm and begin receiving the medicine. "We tried to minimize the number of people getting a placebo," says Charles Baum, the global clinical leader for the drug at Pfizer. Bernie Kaplan, 64, who was diagnosed with GIST in 2000 is enrolled in the Pfizer trial. When the first assessment showed that his tumors had grown, "I was praying I was on placebo," he says. It turned out he had been given a sugar pill. When he started receiving the drug, his tumors shrank. Many pharmaceutical companies say the very nature of these new cancer drugs makes it imperative to have a placebo arm for comparison. Unlike traditional chemotherapy, which is designed to shrink or eradicate tumors, many of these drugs aim to stop or slow tumors' growth and allow someone to live with their cancer. This makes it harder to measure if it is the drug that is working, or whether someone simply has a less-aggressive tumor. In addition, some of the diseases these drugs are targeted at have no other therapy against which a new drug can be compared. Bayer, which is testing its BAY 43-9006 in kidney-cancer patients, adopted a placebo-trial design in its Phase III trial of the drug that began in October 2003. This weekend, the company reported extremely promising results with an earlier-phase trial of the drug -- 37 out of 106 kidney-cancer patients had their tumors shrink 25 percent or more, and 38 had stable disease. Early positive results such as this make patient-advocate groups even angrier that some patients in later trials won't get any drug, effectively meaning they will die. A group of patients met with Bayer in December to discuss the trial design but, says patient advocate Steve Dunn, "they wouldn't budge." Susan L. Kelley, Bayer's vice president for product development in oncology, says pharmaceutical companies are trying to do the right thing. She says there are no options for kidney-cancer patients against which to compare the new drug. And, Dr. Kelley says, the company cannot allow patients on placebo whose tumors grow to then receive the drug, because "it would confound our ability to follow survival. We need definitive evidence that the drug is active."