Cancer #1 Killer

[gpawelski]

The Associated Press reported that Cancer is the Top Killer for Those Under 85. There has been no real progress in the treatment of most common forms of cancer. Recent NCI data showed that U.S. cancer mortality rates have increased and age-adjusted cancer mortality rates in response to treatment have not improved in several decades, despite the introduction of many new drugs. There is a mind-set of cancer culture that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs, that rewards academic achievement and publication over all else. Tumor shrinkage should not be the criteria for approving cancer drugs.

The January 10, 2002 issue of the New England Journal of Medicine noted that 20 years of clinical trials yielded survival improvement of only 2 months for patients with advanced lung cancer. It also pointed out that oncologists at a single institution may obtain a 40-50% response rate (not cure) in a tightly controlled study, but when these same studies are administered in a real world setting, the response rates (not cure rates) decline to only 17-27%.

In the March 15, 2004 issue of the Journal of Clinical Oncology, an editorial stated that a review of all the large, prospective, randomized trials published comparing the newer taxane-based regimens, none of these regimens have increased either complete response rates or overall survival, with median survivals remaining at two years or less. This is precisely the same results which were being obtained 30 years ago.

The results of nearly 30 years of clinical investigation in the treatment of patients with cancer, neither standard or high-dose regimens had done a great deal to improve the outcome of patients. For over the past 20 years, they relentlessly combined chemical agents in various regimens with ever-increasing dose intensity and the survival for patients is exactly the same, less than two years. Not a hint of significantly improved survival.

In the March 22, 2004 issue of Fortune, an extensive expose of why there has been no progress in drug treatment of cancer in three decades, the author writes that it is not localized tumors that kill people with cancer, it is the process of metastasis, 90% of the time. Aggressive cells spreading to the bones, liver, lungs, brain or other vital areas, that are wreaking havoc. You'd think cancer researchers would be bearing down on the intricate mechanisms of invasion and spread? However, according to a Fortune examination of NCI grants going back to 1972, less than 0.5% of study proposals focused primarily on metastasis, trying to understand its role in cancer or just the process itself. Of nearly 8,900 NCI grant proposals awarded in 2003, 92% didn't even mention the word metastasis.

So pharmaceutical companies don't concentrate on solving the problem of metastasis (the thing that really kills people); they focus on devising drugs that shrink tumors (the thing that doesn't). There is a national problem in the way we treat the problem. It is time to set aside empiric "one-size-fits-all" treatment of cancer for "individualized" treatment based on testing the individual properties of each patient's cancer.

The Fortune article is one of the most complete and revealing on the subject; a must reading for anyone who wants to understand the US healthcare's mistaken direction.

http://blog.aperio.com/articles/Fortune_Cancer.pdf

[gpawelski]

On most cancer message/discussion boards, one of the most common themes is that of "chasing mets" (metatasis). Cancer patients are chasing mets because of the wrong type of chemotherapeutic regimens for their type of cancer histology. But why do patients with histologically similar tumors respond differently to so-called "standard" drug treatments? That is one of the main problems associated with chemotherapy. Patient tumors with the same histology do not necessarily respond identically to the same agent or dose schedule of multiple agents.

Medical oncologists select a drug and must wait to see whether it is effective on a particular patient. Conventionally, oncologists rely on clinical trials in choosing chemotherapy regimens. But the statistical results of these population-based studies might not apply to an individual. And when patients develop metastatic cancer, it is often difficult to select an effective treatment because the tumor develops resistance to many drugs. For many cancers, especially after a relapse, more than one standard treatment exists.

A cell culture assay is a diagnostic test (not a treatment) to help measure the "efficacy" of cancer drugs. They cannot make the cancer drugs do better, it can only measure the "best" probability of successful drugs. This is in stark contrast to "standard" or "empiric" therapy (also called physician's choice therapy), in which chemotherapy for a specific patient is based on results from prior clinical studies.

Laboratory screening of samples from a patient's tumor (if available) can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents. It can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient. This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free and overall survival.

It would be highly desirable to know what drugs are effective against particular cancer cells before cytotoxic agents are systemcially administered into the body. Cell culture assays are clinically validated drug tests on living (fresh) specimens of cancer cells to determine the optimal combination of chemotherapy drugs. These assays are specifically tailored for each individual patient based on tumor tissue profiling, with no economic ties to outside healthcare organizations, and recommendations are made without financial or scientific prejudice.

Recommendations are designed scientifically for each individual patient. Various assays are performed on a tumor sample to measure drug activity (sensitivity and resistance). This will determine not only what drug or combinations of drugs will not effectively work, but which will be most effective for an "individual's" cancer. Then a treatment recommendation is developed through what is known as "assay-directed" therapy.

http://www.rational-t.com/

http://www.precisiontherapeutics.com/

http://weisenthalcancer.com/index.htm

[Donna G]

I truely agree that not enough is being done but there is hope. I have heard these doctors speak at the Twin Cities Thoracic Onocology Consortium.

Robert Kratzke, M.D., and Michael Maddaus, M.D., are using a molecule-based technique called polymerase chain reaction (PCR) to detect lung cancer micrometastases, cells too small to otherwise be detected. In this nationwide study, the largest of its kind, Kratzke and Maddaus are evaluating whether PCR techniques can reliably predict .cancer recurrence or poor treatment outcome in patients with the most common type of lung cancer.

In a study that could allow physicians to make an accurate prediction of cancer recurrence risk, Robert Kratzke, M.D., and Michael Maddaus, M.D., found that the technique quantitative reverse-transcriptase PCR can identify metastatic lung cancer cells in each lymph node. If left untreated, undetected metastatic cells can form new tumors. Their study was published in Journal of Thoracic and Cardiovascular Surgery, March 2002.

http://jtcs.ctsnetjournals.org/cgi/cont ... /123/3/484

Donna G

[gpawelski]

Good information Donna. Add that to some technologies that already exist with some that are coming to fruition, and there is endless possibilities for a new paradigm in cancer care.

Gene Expression assays are panels of markers that can predict the likelihood of cancer recurrence in various populations.

Chemosensitivity testing is a test for drug activity against a tumor.

Pharmacogenomic testing is a test to identify patients who are likely to have the most (or least) toxicity.

By testing the gene expression markers of a patient, oncologists can identify those patients unlikely to benefit from adjuvant chemotherapy from those that would. If the patient needs adjuvant chemotherapy, by testing the patient's tumor cells and testing the patient toxicity tolerance, the oncologist can select drugs that have a higher probability of being effective for an individual patient rather than selecting drugs based on the average responses of many patients in large clinical trials.

What a cancer patient would like ideally, is to know whether they would benefit from adjuvant chemotherapy (something gene expression assays may be good at). If so, which active drugs have the highest probability of working (something chemosensitivity testing is very good at) and are relatively non-toxic in a given patient (something pharmacogenomic testing should be good at).

[john]

There is research into the idea of cell adhesion and metastasis. One protien that has been identified is E-cadherin.

There is also some ideas that cancer has unusual cell surface carbohydrates that make them "slippery"

Additionally there is research into MMP-9, and how it promotes invasion.

Remember another big problem with cancer is that it mutates. So if one gets a snapshot of the gene expression at time X it might not be the same some many days later.

Many times drugs work for a while, but once the cancer mutates, it is no longer susceptible to the drug.

http://mayoresearch.mayo.edu/mayo/resea ... disLab.cfm

I think after a while proteomics will eventually pay off, but it will take time. There are 30,000 genes, but there are millions of proteins that the genes express.

http://www.ludesi.com/tibet/chamdo/temp ... ageid=1070

[gpawelski]

Title: ASCO MEETING: Taxol Plus Carboplatin Fails To Show Clinical Advantage Over Standard Regimen In NSCLC

URL: http://www.pslgroup.com/dg/FE506.htm

Doctor's Guide

May 18, 1999

ATLANTA, GA -- May 17, 1999 -- Total drug costs for Bristol-Myers Squibb Co.'s Taxol (paclitaxel) Injection plus carboplatin for non-small-cell lung cancer (NSCLC) were five times those of Glaxo Wellcome Inc.'s Navelbine (vinorelbine tartrate) Injection plus cisplatin according to results of the phase III, multicentre Southwest Oncology Group (SWOG) Study 9509.

The study of 444 patients was presented at the 35th annual meeting of the American Society of Clinical Oncology (ASCO) and made available to the media by Glaxo Wellcome. Navelbine-cisplatin was established as the SWOG standard of care in a study presented at ASCO in 1996.

The resource utilisation results of SWOG 9509 showed that drug costs and total medical costs (median per patient) were lower for the Navelbine-cisplatin arm ($4,116 US and $17,876 US) than for the Taxol-carboplatin arm ($19,895 US and $34,693 US). These results were the only significant difference between the two treatment regimens -- no significant differences in survival, response rates or quality of life were seen between the Navelbine-cisplatin and the Taxol-carboplatin treatment arms.

The primary objective, according to Karen Kelly, MD, University of Colorado, the study's lead investigator, was to determine whether Taxol-carboplatin offers a survival advantage over the SWOG standard regimen Navelbine-cisplatin. Based on the study design, the Taxol-carboplatin combination would have been superior if median survival was increased by 50 percent.

The study showed that both treatment arms had median survival, the most important clinical endpoint, of eight months and response rates of 27 percent. One-year overall survival was also reported to be similar for the Navelbine-cisplatin and Taxol-carboplatin arms (36 percent and 38 percent, respectively). It is notable that the Navelbine-cisplatin results of this study were remarkably consistent with those of the SWOG 9308 study, after which Navelbine-cisplatin became the new SWOG standard regimen for NSCLC.

A comparison of toxicities showed that the Navelbine-cisplatin arm was associated with significantly more grade IV neutropenia, leukopenia and nausea and vomiting; whereas the Taxol-carboplatin arm was associated with significantly more grade III peripheral neuropathy. Quality of life was maintained (improved or stable) in both treatment arms, which may indicate that although the two arms had different toxicity profiles, tolerability was similar based on patient quality of life assessments. Nausea and vomiting are treatable short-term effects of therapy. In contrast, peripheral neuropathy may have long-term consequences.

Navelbine Injection is indicated as a single agent or in combination with cisplatin for the first-line treatment of ambulatory patients with unresectable, advanced NSCLC. Navelbine is the only single agent approved by the FDA in 20 years for the treatment of advanced NSCLC. In addition, Navelbine is indicated in combination with cisplatin and offers clinical benefit as evidenced by response rates and overall survival. Navelbine is contraindicated in patients with pre-treatment granulocyte counts less than 1,000 cells/mm3. Granulocytopenia is dose limiting but is generally reversible and noncumulative over time.

In two large phase III studies, Navelbine plus cisplatin demonstrated an increase in overall response rate and median survival time, compared with cisplatin alone or cisplatin combined with vindesine.(A-C) The ASCO non-small-cell lung cancer expert panel has recommended this combination as among those that are effective first-line therapies in advanced unresectable disease.

[Larry]

This discussion i've found very informative and some what supportive of my view's. I have this feeling that if a person changes his/hers life styles and refuse the Chemo routine that your siurvival odd's are just as good if not better. In fact there are some studies out that seem to support that view.

Were all going to die of something so why not feel as good as we can while we can.I set here day after day watching how miserable my wife feel's, not that she's in all that much if any pain it's just the general not feeling good that is so bad.She has hinted at stopping treatment and if she chooses to do so i'll support her as of right now she is alive but no life if you understand my point.

I read where every one is praying for this one or that one and yet the result's never seem to change.I believe in GOD and attend mass weekly but i'm loosing my faith in praying and beginning to think it is just wishfull thinking.Enough of my emotional Roller coaster and back to subject at hand. I read that in a survey taken by some group that 80% of onocologist say they would not take Chemo if DX'ed with Cancer.And another place i read that late DX'ed staged prostrate Cancer victim's lived longer if they recieved no treatment.

I think most Doctor's have become like Car Mechanic's they open the book and replace the part and off you go. I know that one feel's like were on a assembly line with dealing with the Doctor's and they seem to have lost the one on one approach.