ADDITIONAL INFORMATION REGARDING OVARIAN CANCER & RADIATION/CHEMOTHERAPHY BY GREG PAWELSKI
So Much For Carboplatin Being A Death Sentence
Based on the clinical trials, results showing no difference between single agent platinums (cisplatin or carboplatin) versus platinum/Taxol (GOG Trial # 132, ICON3), the British National Institute for Clinical Excellence (NICE) determined that platinum/Taxol should no longer be considered as "standard therapy"
click here for a summary and
click here for PDF file of document reviewing data and explaining recommendations) and that a range of therapies are equally acceptable. In the USA, where the administration of platinum/Taxol has been much more profitable to the treating oncologist than single agent platinum, there has been the dogged insistance that platinum/Taxol remains "standard," despite clear lack of support for this position, based on the entirety of the clinical trials literature.
The ICON-4 trial is misleading.
It took patients who relapsed with so-called "platinum sensitive" disease (relapse > 6 months following last chemotherapy). They were randomized between platinum/Taxol and single agent platinum. More than 80% of the platinum/Taxol group got carboplatin (as opposed to cisplatin). These all got carbo at a dose of 5 (AUC), which was the same dose given to the single agent platinum group. Also, a lot of the patients had been treated with single agent platinum as first line therapy (it was a European trial). The advantage of the combination was modest (10% improvement in progression free survival at one year). Plus, the combination group got more intense therapy (same dose of carbo plus the addition of another drug). Plus, a lot of the patients were "seeing" Taxol for the first time.
If ever given the chance to do a trial, assay-directed chemotherapy will "defeat" any fixed regimen (combination or single agent).
The problem is the complete irrelevance of this study to the question of first line therapy. This question has been asked and answered. Twice. GOG-132 and ICON-3. Platinum-Taxol is NOT superior to single agent carboplatin and single agent cisplatin. I still can't believe that an oncologist would actually tell a patient that single agent platinum would be a "death sentence." This is more "Lies and the Lying Liars Who Tell Them" type stuff.
It has not been shown that platinum-based combination therapy is superior to single agent alkylator therapy. No substantial benefit has been found in giving ovarian cancer patients this therapy. Clinicians have found that the toxic effects of this treatment can cause a lower quality of life for these patients.
Taxol does not improve standard first-line ovarian cancer treatment. Studies (Lancet - August 17, 2002 edition) suggest that for initial treatment of women with ovarian cancer, widely used standard drugs are equally as effective as treatments that include Taxol and Carboplatin and may be considered the preferred treatment as they have fewer side effects. The results of these studies doesn't mean that Taxol has not role in the treatment of ovarian cancer, but they allow doctors and ovarian cancer patients to have choices according to each individual's needs.
Twenty-five years of clinical trials in ovarian cancer have never proven that platinum-based combinations are superior to the single agent alkylators used since the 1960's and it has never been proven that expensive platinum/Taxol combinations are superior to single agent cisplatin or single agent carboplatin (carboplatin having much lesser side-effects). Two large, unrefuted studies (GOG-132 and ICON-2) showed that single agent carboplatin was at least as good and in some respects better than platinum/Taxol. Paclitaxel (Taxol) plus carboplatin failed to achieve superiority over carboplatin alone in the ICON-3 study.
There are few more imprecise and drastic measures than chemotherapy as a treatment for cancer. The process involves poisoning a patient's system with toxic chemicals in an effort to kill malignant cancer cells. As one who has personnally seen a loved one suffer, I can attest to its destructive and debilitating side effects. Patients generally need steroid pre-treatment and many have a severe reduction in white blood cells.
There has been no real progess 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.
Investigators rely on models that are grossly deficient at predicting success. Hundreds of cancer drugs are pushed into the pipeline and many are approved by the FDA, even though their proven activity has little to do with curing cancer. Hundreds of clinical trials of one-size-fits-all therapy in tens of thousands of patients having results that have trivial hypotheses and produce no progress.
Proof of efficacy of a cancer treatment such as chemotherapy requires a randomized trial in which it has been shown that the group treated with chemotherapy experienced significantly increased survival when compared to that of an untreated group. This has never been done. Most claims for the efficacy of a chemotherapeutic agent comes from trials showing shrinkage of tumors or from comparison of survival rates of unmatched groups over time. Unless tumor shrinkage is accompanied by evidence of increased survival, the treatment cannot be claimed to be effective.
Additionally, in clinical trials, many patients are excluded because they could not complete the rather arduous treatment. So randomized comparisons are of healthier treated patients against all the controls, rendering a lot a trials flawed.
Commentary On Oral-Dose Targeted Chemotherapy Under Medicare
Under previous law, Medicare covered chemotherapy as well as radiation treatment for cancer patients, but did not pay for oral-dose anti-cancer drugs, unless they were available in both oral and injectable form. Medicare Part B covered a total of seven oral-dose anti-cancer drugs, under this provision. Older Americans were being denied access to the latest generation of cancer drugs simply because these therapies came only in pill form.
The new Medicare bill offered patients benefits they did not have before. There is now some coverage for oral chemotherapy drugs, which were not available before. Since April of 2004, $200 million was available so that some Medicare cancer patients would have transitional coverage for these drugs, until the bill goes into full effect in 2006. Although some benefit was realized, more might have been achieved if ASCO (American Society of Clinical Oncology) and other groups had lobbied as much for the oral chemotherapy drug issue as they did for office-practice expense reimbursement. ASCO fought long and hard to retain the Chemotherapy Drug Concession.
Increasingly, oral-dose anti-cancer drugs ar
e found to treat cancer effectively and seen as an intergral and necessary part of a patient's cancer care. A number of these breakthrough cancer drugs came on to the market that are only in oral form and previously not reimbursed under Medicare. Patients were being forced to compromise their cancer care due to Medicare not covering many of these life-saving therapies.
The new legislation started the process of providing access to a full range of the latest cancer-related prescription drugs at manageable costs to enhance the quality and standard of treatment for cancer. Cancer patients under Medicare are now able to rely on treatment decisions that are dictated by good medicine and not just economics. Medicare recipients were being relagated to treating their diseases with older, more toxic infusional chemotherapy agents at a time when new and more promising cancer drugs were reaching the market.
The new targeted, relatively non-toxic oral anti-cancer drugs are based on a variety of biological mechanisms that essentially stop cancer from spreading. Targeted cancer therapies use drugs that block the growth and spread of cancer. They interfere with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than current treatment protocols and less harmful to normal cells.
Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die (apoptosis) and new cells take their place. Sometimes this orderly process goes wrong, new cells form when the body does not need them and old cells do not die when they should. These extra cells can form a mass of tissue called a growth or tumor (lesion). Cells in cancerous (malignant) tumors are abnormal and divide without control or order.
These anti-proliferative agents have such names as signal-transduction inhibitors (cascade of cellular and biochemical events), farnesyltransferase inhibitors (cell death inducer) and angiogenesis inhibitors (new blood vessel blocker). Targeted cancer therapies interfere with cancer cell growth and division in different ways and at various points during the development, growth and spread of cancer. By blocking the signals that tell cancer cells to grow and divide uncontrollably, targeted cancer therapies can help to stop the growth and division of cancer cells.
These new products are an indispensable new feature of quality cancer care and will replace, enhance or even make more effective therapies that are largely based on intravenous administration (infusion therapy).
Compared to infusional therapy, oral-dose anti-cancer drugs can make receiving cancer treatment more convenient for patients by allowing flexibility in taking medication without disrupting work or other activities. They can often result in less time spent in office-based oncology practices because of the absence of intravenous administration and its related side-effects.
Targeted cancer therapies will give doctors a better way to tailor cancer treatment. Treatments may be individualized based on the unique set of molecular targets produced by the patient's tumor, and these important treatment advances will require individualizing treatment based on testing the individual properties of each patient's cancer. Chemosensitivity Testing (Cell Culture Drug Resistance Testing) can improve patient survival in chemotherapy for cancer.
These new differences in therapy hold the promise of being more selective, harming fewer normal cells, reducing side-effects and work to improve the quality of life for people with cancer and can translate into savings for them and overall for the health care system.
Changing the Identity of Medical Oncology
The new Medicare Bill (MMA) still has major flaws, in that it continues to provide incentives to administer chemotherapy, in the same way that surgeons have a financial incentive to recommend surgery. Additionally, it is a certainty that there will be large differences between the profit margins of administering different drugs, providing continuing incentives to base drug selection on profit margin. However, the new system is clearly an improvement from the standpoint of cancer patients, taxpayers, and advocates of basing drug selection on individual tumor biology, rather than on a least common denominator approach which invites "conflict-of-interest medical decision-making."
What this shows is that simply reducing reimbursement for drugs isn't the answer to the biggest problems, which are financial incentives for infusion therapy over oral therapy or non-chemotherapy, and financial incentives for choosing some drugs over others. One example, oncologists will just not give gemcitabine and /or irinotecan, but instead will choose drugs which are profitable.
Oncologists should simply submit copies of their drug invoices and get paid the exact cost of the drugs, plus a small markup for administrative expenses. They should get reimbursed for the costs of actually adminsitering the drugs, plus a small markup which is not enough of an incentive to treat with infusion therapy, rather than just writing a prescription for drugs which would be filled at a pharmacy.
Under the new Medicare Bill (MMA) medical oncologists will be reimbursed for providing evaluation and management services, making referrals for diagnostic testing, radiation therapy, surgery and other procedures as necessary, and offer any other support needed to reduce patient morbidity and extend patient survival.
Because oral-dose drugs ultimately deliver on their promise of combining equally efficacious therapy with better adverse event profiles and easier administration, they will rightfully gain their appropriate share of the marketplace, again.
What needs to be done is to remove the profit incentive from the choice of cancer treatments. Patients should receive what is best for them and not what is best for their oncologists.
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Last Updated On: 02/08/2006
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