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1. Eric
   M.D. Anderson Cancer Center is taking a new look at how to evaluate new medicines and treatments for cancer. “We need to rethink how we design and conduct clinical trials in the U.S.” says Dr. Donald Berry, one of its scientists. He feels that we should turn the ‘statistical method’ used to evaluate new drugs on its head, stating that it limits innovation and learning.
   What he’s talking about is the adoption of the Bayesian method of science because it is more in line with how science works. They are putting this approach to the test with more than 100 cancer-related phase I and II clinical trials being planned or carried out using the Bayesian approach. Of course, the Bayesian method is no stranger to the technology of Cell Culture Assay Testing (Chemosensitivity Testing). In fact, it is what gives credit to the accuracy of assay testing.
   Clinical trials test the efficacy (not the accuracy) of a drug. The efficacy of a drug is to produce a desired effect, which is tumor response (shrinkage). Single arm clinical trials provide the tumor response evidence that is the basis for approving new cancer drugs. The Bayesian methology can bring some much-needed “accuracy” to the forefront of clinical trials.
   Clearly, more effective cancer therapies are desperately needed, and after 30 years of investigation aimed at intensified multi-agent chemotherapy, we should look for other avenues of study. In an era of ever-increasing numbers of partially effective cancer therapeutics, there is an obvious need for more accurate methologies. We cannot afford any more ‘trial-and-error’ treatments.

2. My 76 year old mother’s doctor told a room full of worried relatives that he could not remove the tumor from her liver and pancreas, and had to close up the wound. He said there was nothing that could be done, he was specific, NOTHING would help her, not chemo, not radiation. Several hours later when she was lucid, and she asked if chemo and radiation would help, he said yes, and arranged for them. I could not believe my ears! Her suffering was long lasting and horrid. She could not eat, her teeth crumbled because of the radiation. She lasted a while, but her quality of life was extremely poor. I went with her once while she was hooked up to chemo, and she broke down and started to cry, and said she could not take any more of those toxic drugs. After the treatment whe would be deathly sick for several days, not being able to eat anything. My heart broke when I saw that. She was on seven medications before her diagnosis of cancer! I have very little respect for doctors. My brother died of Leukemia 16 months after my mother died. His doctors actually told him that they made a mistake in his protocal for the chemo. They gave him too high a dose, time after time. They cured his cancer but he died from lack of red blood cells, his red blood cell count was down to three, he suffocated to death. He was 58 years old. A doctor friend of his was his friend’s death watch, and had to leave the room as it was bothering him so much to see Jim gasp for air and his chest heaving. His doctor said that if our brother had done nothing at all, he could have lived two more years. He missed out on seeing a new granddaughter born. Now I have learned that oncologists are getting wealthy from handling chemo drugs through government assistance. How unethical. There is a higher court that they will have to answer to, and I think everyone knows who the judge is in that court. What happened to the oath “TO DO NO HARM”?

3. Dr. Andrew C. von Eschenbach, chief of the National Cancer Institute and tapped to be the temporary chief of the FDA is championing the cause of “individualized treatment.” Von Eschenbach has said that our increasing understanding of diseases at “a molecular level” will lead to an entirely new kind of health care.
   “Now, doctors treat illnesses based on how well other people have responded to a given treatment (evidence-based). Soon, they will develop a tailored response built around specific understandings of the patient, the treatment and the disease,” he said.
   “Much of what we have done … has been based on a model of empiricism. Soon, doctors will be able to intervene with medical treatments more effectively matched to a specific patient’s illness. Preparing the FDA for this transformation is among his goals,” von Eschenbach has said.
   The technology needed for producing individualized cancer therapies is already available, but to the frustration of many, did not have the leadership to transform this mode of treatment to clinical oncology. Now we have that leadership.
   The needed change in the “war on cancer” will not be on the types of drugs being developed, but on the understanding of the drugs we have. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them.

4. Look, I’m not saying oncologists don’t take advantage, but: 1) They do operate by protocol, 2) They do contribute to field research (if not with a present case than by being the main specialty of medicine and surgery that sets that precedent), 3) Keeping said database is not easy, moreover, it IS complicated and expensive and not to the extent required, ‘what they do anyway, 4) They hope and treat accordingly (You wouldn’t have it any other way). This is not to say that they could be more discretionary but that’s Monday morning quarterbacking at its worst.
   Give ’em a break
   P.S. I’m a practicing pediatrician and former medical director for a number of health plans
   Please also see the following (cut and paste) URL, my website–http://www.managingmanagedcare.com/,ManagingManagedCare.com} – – > Evidence-based Medicine (EBM) – (D}x), (T}x) and (R}x – – > Disease and Clinical Conditions – – > and then, http://www.managingmanagedcare.com/discus/messages/225/215.html?1131108684 for “Cancer Cures and Controversies.”

5. Eric
   There is a need for changes in our approach to the chemotherapy of the most common forms of adult cancers. The experience in metastatic breast cancer shows that back in the early 70s, the median survival for metastatic breast cancer was just under two years. Today, it is just under two years. Despite scores of prospective randomized trials involving tens of thousands of patients, showing that response rates (tumor shrinkage) have gone up, yet the overall survival rates have not improved.
   You give more aggressive chemotherapy by utilizing combinations, high dose therapy, etc, in diseases like metastatic breast cancer and ovarian cancer and you increase response rates, but you don’t improve overall survival. The true situation is that ineffective, aggressive chemotherapy can diminish not just quality of life but also quantity of life, through organ toxicity, immunosuppression, and inducing genetic mutations. The result is no improvement in the treatment of the most common forms of metastatic cancer over the past 30 years.
   You want to reserve aggressive therapy for those patients who will derive more benefit than harm, while identifying the most promising treatment regimens for everyone. In patients with tumors very resistant to cytotoxic chemotherapy in general, the most promising treatments may include angiogenesis inhibitors, growth factor inhibitors, or more integrative holistic therapy approaches.
   A better approach may be not to give more aggressive, toxic, mutagenic and immunosuppressive combinations, but to give targeted single agents, or to give the least toxic and mutagenic “active” combinations. Higher response rates don’t necessarily lead to improved clinical outcomes.
   The era of empiric, aggressive multi-agent cytotoxic chemotherapy for adult solid tumors should come to an end. We should put much more emphasis on matching the treatment to patient, though the use individualized testing, have more respect for minimal partial response or stable disease, when it can be achieved through the use of the least toxic and mutagenic drug regimens, and reserve the use of higher dose therapy or agressive combination chemotherapy to those fortunate patients with tumor biologies most amenable to attack and total or near-total destruction by these aggressive treatments.
   There are over 100 different therapeutic drug regimens out there (400 are in the pipeline). Any one or combination of them can help cancer patients. The system is overloaded with drugs and under loaded with wisdom and expertise for using them.

6. Greg- what do you mean by “aim higher”? How would you design trials for new drugs? Who would/ should pay for them? If the drug manufacturers must pay– then the conflict of interest will exist. New drugs cost, currently, 100s of millions of dollars to get to market. Would you have the public fund trials of privately developed drugs? Who should get profits?

7. The problem is that, all too often, the “best” therapy is so poor that it does not deserve the exhalted status of “standard” therapy.
   Current approaches to cancer therapy are too often ludicrously ineffective and “progress” over the past 30 years has too often been virtually non-existent, from the viewpoint of anyone who is not impressed when a 2,000 patient prospective randomized trial produces a “significant” improvement in median survival which translates out to an 18.4 month median survival versus a 17.1 month median survival and that means that everyone should receive the treatment producing the 18.4 month survival, even when the next three trials fail to confirm this “advantage.”
   I think ASCO and NCCN are protecting the status of treatments which are only marginally and minimally and inconsistently effective. This prevents serendipitous and fortuitous discovery. Truly effective treatments don’t need prospective randomized trials. If we’d never done a single prospective, randomized trial in ovarian cancer, for example, I am certain that we’d be no worse off than we are today and we’d probably be a lot better off. Same thing for the chemotherapy of metastatic breast cancer and lung cancer.
   We need to aim higher.

8. The Oncology Industrial Complex is astonishing. In the course of our research on the evolution of specialty drug management, oncology continues to stand out for its well-organized resistance to anything that would challenge its independence and authority. The changes to Part B may achieve somethign despite this: as more and more commercial insurers move to adopt the Medicare payment rate (ASP+6%), pressure on providers will grow. Since payers aren’t buying the “I’ll-start-sending-patients-to-the-hospital” argument, I think this is going to have a significant impact on cancer medicine, particularly in terms of drug choice at the margins. We predict a rationalization in drug use within the next 12-18 months.
   One final point: I recently asked the Medical Director of a health plan in Louisiana whether his organization had had any luck getting oncologists to change their practices. He sighed and said, “Well, we’ve gotten them to stop administering drugs in the funeral home.”

9. Reminds me of the movie “Whit,” which was also a play: the story of an English professor who gets cancer and is pressured by research oriented physicians to endure excrutiating treatment that helps their study even though a more gentle plan may have been better.
   The thought of being a patient is downright scary when other people are making the crucial decisions that affect your life and health.