1. Researchers from Turkey had confirmed that a regimen of Carboplatin and Gemzar was effective for the treatment of recurrent platinum-sensitive ovarian cancer. Participants in the study included women diagnosed with epithelial ovarian cancer whose disease had recurred more than six months after discontinuing first-line platinum-based chemotherapy. It was concluded that the combination of Gemzar and Carboplatin is a feasible treatment option for patients with platinum-sensitive recurrent ovarian cancer. The details of this phase II study were reported in the February 2005 issue of Gynecologic Oncology.

The superiority of the addition of Gemzar to Carboplatin (14% vs 6%) for the treatment of advanced ovarian cancer that has recurred in the clinical trial stated in this post, seems to merit widespread use. Gemzar and Platinum (whether Cisplatin, Carboplatin or Oxyplatin) has been a "powerful" drug combination found effective against a range of cancers, discovered through drug sensitivity tests reported at the 34th annual meeting of the American Society of Clinical Oncology in Los Angeles, CA.

However, giving this combination to everyone would not be that helpful, because the organ toxicity, immunosuppression, and mutagenicity of the combination cancels out in many patients, the gains in a few, fortunate patients. More emphasis should be put on matching treatment to the patient and having more respect for minimal partial response or stable disease.

What you may want to do is to reserve the 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 medicine approaches.

It could be that a better approach for treating recurrent cancer is not to give more aggressive and toxic and 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.

Posted at 3:32PM on Sep 19th 2006 by Gregory D. Pawelski

2. "discovered through drug sensitivity tests reported at the 34th annual meeting of the American Society of Clinical Oncology in Los Angeles, CA."

The approval of the combination is not based on drug sensitivity tests of a decade ago, but a recently completed, evidence-based, study:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16966687&query_hl=5&itool=pubmed_docsum

For now, "the Gynecological Oncology Group has approved the concept of performing a trial to assess assay directed therapy for patients with platinum resistant epithelial ovarian carcinoma. We await the results of this and other "assay directed" trials with the hope that the time for successful tailored therapeutics has finally come."

http://www.jco.org/cgi/content/full/23/15/3641

Posted at 7:18PM on Sep 19th 2006 by Michelle

3. If I'm correct and they have not changed the design, GOG intends to treat patients and only then use the assay to select therapy. A prior paper already established that the assay can identify a small percentage of patients who will not respond (i.e. EDR), but then when the results were used to select an non-EDR alternative, it did not provide responses. Thus, using non-EDR drugs will not improve outcomes. In this light, the EDR assay has the advantage of telling you who will not respond but cannot in any way change the death sentence by selecting an active alternative. Perhaps the EDR can give more time to select a mortuary. The best trial is a first-line study, no prior therapy, assay versus a control.

However, greed and certitude in the power of the dollar have once again clouded judgement. Not everyone is willing to sell his principles so cheaply. The persons making these decisions are not friends of cell culture assays, but they are smart and cynical enough to accept baksheesh from the very persons whose technology they are bent upon discrediting. It's death by clinical trial, the academician's weapon of choice, which they wield expertly. These guys know very well what they are doing. In essence, it's "Thanks but we've heard these arguments before - no need trouble yourself by repeating them." Good grief, they aren't even trying to make it appear as though they are doing the right thing.

Different methods of assay endpoint results should be applied in choosing a particular drug regimen to be used in treating an individual patient's cancer. Different methods of assay endpoints will sort the different reasonable treatment regimens into the different groups (above-average, average, below-average and very below-average), which would direct attention away from regimens "less" likely to provide benefit and toward regimens which are "more" likely to provide benefit.

In the meantime, over the last 15 years, there is the gyn-onc who doesn't get paid for 40% of all the care he provides. He'll take a patient who is medically indigent after using up all of her insurance and, knowing he won't make a penny, will start operating at 9 AM and will proceed to spend the next twelve hours removing every last vestige of tumor. And then spend many hours over the next week providing post-op care. And then gives assay directed therapy with drugs which would make him no money, even if the patient did have insurance. All in the science of saving lives.

I believe the best one in the series of JCO "Correspondence" letters is the one from Dr. Michael Castro. The only one who had no conflict of interest, and his commentary was both reasonable and wise.

http://www.jco.org/cgi/content/full/23/15/3645

Posted at 8:33PM on Sep 19th 2006 by Gregory D. Pawelski

4. A clear, rational, concise, factual, thoughtful, fearless response

http://www.jco.org/cgi/content/full/23/15/3646

to the URL posted by Mr. Pawelski and to those who create fear in cancer patients through use of such emotionally-charged phrases like:

"greed and certitude"
"death sentence"
"select a mortuary"
"sell his principles"
"bent upon discrediting"
"cynical enough to accept [bribes]"
"death by clinical trial"

I wonder if he talks to cancer patients like this to their faces as they undergo treatment?

He talks to them like that here.

Posted at 11:09PM on Sep 19th 2006 by Michelle

5. Correspondence equally as pointed as the URL posted by Michelle A.

http://www.jco.org/cgi/content/full/23/15/3641

http://www.jco.org/cgi/content/full/23/15/3643

"Peer review can be performed successfully only if those involved have a clear idea as to its fundamental purpose. Most authors of articles on the subject assume that the purpose of peer review is quality control. This is an inadequate answer. Peer review must aim to facilitate the introduction into medicine of improved ways of curing, relieving, and comforting patients. The fulfillment of this aim requires both quality control and the encouragement of innovation. If an appropriate balance between the two is lost, then peer review will fail to fulfill its purpose."

Horrobin, D.F. (1990) The philosophical basis of peer review and the suppression of innovation. JAMA 263(10):1438-41.

Posted at 2:42AM on Sep 20th 2006 by Gregory D. Pawelski

6. "Some experts have been calling for either the F.D.A. or the Center for Medicare and Medicaid Services, which regulates clinical labs, to bolster regulation of genetic tests.

“There’s been a gaping hole in the oversight of genetic tests,” Dr. Hudson of Johns Hopkins said. “We have seen a tenfold increase in the number of genetic tests available over the last decade and an even greater increase in the complexity of those tests.”

F.D.A. officials said such tests needed regulation because the algorithms used are usually proprietary, making it hard for doctors to interpret the test results.

“It’s important for the agency to look at the data on which these tests are developed,” Dr. Daniel Schultz, the director of the F.D.A. Center for Devices and Radiological Health, said in an interview.

The F.D.A. said it would decide case by case what to do about the tests already on the market. Some might have to come off the market until the developer can provide enough data for approval. However, officials said they would work toward the “least burdensome” approach.

Some experts have been calling for either the F.D.A. or the Center for Medicare and Medicaid Services, which regulates clinical labs, to bolster regulation of genetic tests."

$3500 for the Oncotype GX test:
(it analyzes the activities of 21 genes in a sample of breast tumor and then computes a score that is said to be predictive of whether a patient’s cancer will recur and whether she would benefit from chemotherapy) That's a huge amount of money if this test is done on every breast cancer patient with the already massively struggling Medicare orderd to pick up the tab.


Let's get the science right instead of just taking the word of the manufacturers who may be doing good, yet unproven work. Ohterwise it's almost like we're buying something from an infomercial.

http://www.nytimes.com/2006/09/06/business/06drug.html?ex=1158897600&en=6e3a3ea391c5efd1&ei=5070

Posted at 12:49PM on Sep 20th 2006 by Michelle

7. Resistance to change may be active, covert, or organized from vested interests. It is unrealistic to expect independent change to tackle vested interest resistance, but change can signal to those interests, such interventions may be few but telling. Aside from everything we understand about ignorance, misunderstanding, personal and institutional agendas, and profit motive, is the fact that a decade-long campaign of side-door avenues and access-buying was done in the best political tradition.

These vested interests had been agnostic on the use of assays, but supposidly appointed a panel to study them. In the meantime, they want to make certain that they'll still get paid if they choose to use drugs which perform poorly in the assays. However, patients should receive what is best for them and not what is best for their oncologists. Here and there around the world, there are decisions still being made by oncologists who aren't in the pockets of American Big Business. They espouse individual intelligence, integrity and curiosity.

Pithy eloquence from Dr. Castro's correspondence: "should it (assays) be denied to patients, including those who walk in the door asking for it? Such an extreme proscription against (assay) testing outside a clinical trial makes it sound as if the existing data on the subject are largely negative. Yet, the review (of assays) hardly establishes such grounds for a summary admonition. Thus, we should reject their extreme proscription."

Maybe there is a glimmer of hope? A tribute to my dearly beloved spouse and a hundred thousand other ovarian cancer patients.

Posted at 1:54PM on Sep 20th 2006 by Gregory D. Pawelski

8. "Resistance to change may be active, covert, or organized from vested interests."

Luckily, there are those in the assay community who are beginning to perform testing to see if there is any legitimate benefit. Of course, THEY have a vested interest and there are good scientists at these biotechs. They know the importance of good research BEFORE espousing unproven benefit and declaring to cancer patients that they are doomed if they don't get one. (Almost sounds like a guy I know who tells me my family is doomed as terror will overtake us if I don't vote for members of his party.)

So they've begun studies.

"they want to make certain that they'll still get paid if they choose to use drugs which perform poorly in the assays."

No evidence of this cynicism which can't help but create fear in a cancer patient.

"Such an extreme proscription against (assay) testing outside a clinical trial makes it sound as if the existing data on the subject are largely negative."

There is no data. Finally, real clinical benefit is being studied. But, it's just the beginning. No benefit can be claimed. The inference from accuracy to claim of benefit only exists in the minds of the purveyors of imaginary information at this time. I hope it does benefit, but I will not create fear in patients, indicating to them that they have been "given a death sentence" as an incredible small minority (count them on one hand, maybe one finger) would have you believe.

"extreme proscription?"

Ugh. Again.

A tribute?

Posted at 5:54PM on Sep 20th 2006 by Michelle

9. M.D. Anderson Cancer Center is taking a new look at how to evaluate new medicines and treatments for cancer. They are rethinking how they design and conduct clinical trials in the United States. Dr. Donald Berry, one of its scientists, feels that they should turn the 'statistical method' used to evaluate new drugs on its head because it limits innovation and learning.

They adopted the Bayesian method of science (with its algorithms) because it is more in line with how science works. They put 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. 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 methodology 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 methodologies. We cannot afford any more 'trial-and-error' treatments.

http://www.mdanderson.org/departments/newsroom/display.cfm?id=f90987e4-8ebb-4e10-8ed282ec15dd38e9&method=displayfull&pn=00c8a30f-c468-11d4-80fb00508b603a14

Posted at 6:18PM on Sep 20th 2006 by Gregory D. Pawelski

10. Major strides have been made in cancer treatment and detection.

No one needs to die of colon cancer. It's a slow grower.

If you have a close relative with ovarian cancer, get an oophorectomy and watch your odds plummet.

Stop smoking.

Get your prostate checked. It's a slow grower.

Check out this on breast cancer. Wow:
http://www.seniorjournal.com/NEWS/Health/6-09-13-RaloxifeneMakes.htm

A few decades ago you would be cut open and closed, told to go home and prepare for the last weeks or months ahead.

Today it's years.

Research is ongoing. Support candidates who want to spend more of your tax dollars on that research. New therapies may work and many may not.

For a more balanced look at where we currently stand you may want to read this easy, informative article.

http://www.livescience.com/humanbiology/060919_bad_cancer.html

Doomed? Not anymore.

Posted at 6:47PM on Sep 20th 2006 by Michelle

11. Individualized testing of the gemcitabine + platinum combination began in the mid-1990s by Dr. Robert Nagourney, Director of Rational Therapeutics, Inc. Many patients received treatment with this regimen because of individualized testing long before any clinical trials in their particular disease types had ever been published. The contribution of Dr. Nagourney in terms of recognizing the synergistic effects of this combination had been very important in getting clinical trials with this regimen started in a broad spectrum of cancers.

http://www.genengnews.com/news/bnitem.aspx?name=3816301

Posted at 5:17PM on Nov 9th 2006 by Gregory D. Pawelski