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Life Extension Magazine

LE Magazine September 2007
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Life-Saving Cancer Drugs Not Approved by the FDA


By William Faloon and Donna Pogliano

The FDA’s Lethal Impediment

Not only do FDA policies delay life-saving drugs from being approved, but they often keep effective medications off the market forever!

Take the case of Geron, a pharmaceutical company that is aggressively researching and developing a telomerase vaccine that would “teach” the patient’s own immune system to attack cancer cells while sparing other cells.42 If a small company like Geron were to run out of money before it could conclude the expensive clinical trials required for FDA approval, its vaccine research program could come to a grinding halt.

The FDA does have a “compassionate use” exemption that allows cancer patients access to experimental therapies.43 The problem is that the FDA mandates that these cancer patients first fail so-called “proven” therapies. When cancer cells are exposed to “proven” therapies like radiation or chemotherapy, they mutate in a way that causes them to become super-resistant to future therapies. The patient’s healthy cells (including dendritic cells of the immune system) are often seriously impaired when exposed to these “proven” treatments, thus making therapies like Geron’s telomerase vaccine less likely to be effective.

Contrast this with a free choice policy of giving dying cancer patients the chance to try Geron’s new vaccine immediately. Under this system, it could be possible to determine whether the vaccine worked within months, as opposed to the multi-year period currently mandated by the FDA. If it worked, then millions of cancer patients’ lives would be saved. If the vaccine failed, then these terminally ill cancer patients will have died as they would have anyway, willingly accepting the risks involved, and sacrificing their lives in the hope of saving the lives of those who come after them.

Getting the Best Therapies to Cancer Patients Now!

There are effective therapies and cancer detection methods approved by governments in countries other than the USA. Medical articles published in peer-reviewed journals read by physicians around the globe attest to the efficacy of such treatments and methodologies. A risk-free example of what Europeans have that Americans don’t is a diagnostic procedure called Combidex®. This procedure can detect lymph node metastases as small as 5 mm with a 95% level of accuracy.44 Combidex® has the potential to revolutionize the practice of oncology, yet the FDA has failed to recognize its potential and grant approval in the US. Combidex® involves the use of MRI (magnetic resonance imaging) in conjunction with a novel contrast agent—nanoparticles of iron. The very same iron nanoparticles are used to correct the anemia commonly occurring in patients on renal dialysis. Over 4,000 patients have been studied in the Netherlands with Combidex®. But Americans and Canadians wishing to have this study to most accurately document the extent of their cancer and to then choose treatment strategies that will optimize the chance of success have to travel to the Netherlands.

The FDA rejected the approval of Combidex®. Apparently, it would rather have patients go through surgery and/or radiation and fail either or both therapies due to lack of proper staging of the disease. Given this, it is no wonder that more patients are not cured of cancer, and that the cost of healthcare is so outrageous.

We need to bring proven diagnostic tools like Combidex® to patients in the USA who agonize over whether or not their cancer is systemic, and who have to decide whether to undergo local or regional therapies like surgery and/or radiation, when in reality their cancer may already be outside of the anatomic areas that can be cured by such therapies.

Photodynamic therapy (PDT) is approved for treating skin lesions, non-small cell lung cancer, and cancerous conditions of the esophagus, but its potential in treating a broader range of cancers has been largely overlooked.45

Abraxane® is now approved for use in breast cancer, but it is still not approved for anything else, despite evidence that it almost certainly will be effective against prostate and other cancers that have shown sensitivity to chemotherapy with taxanes such as Taxol® or Taxotere®.46 Abraxane® is another example of nanotechnology, as is Combidex®. In fact, Abraxane® is simply a nano-particle of Taxol® that is bound to albumin. Abraxane® is nab-paclitaxel, which simply stated is nanoparticle, albumin-bound Taxol®. Such nanoparticle technology allows for better penetration of the anti-cancer agent into the tumor’s vascular plexus. Additionally, tumor cells have albumin receptors that appear to attract the nab-paclitaxel (Abraxane®). Abraxane® has been approved by the FDA for treatment of metastatic breast cancer only. The FDA has required the manufacturers of Abraxane® to do further clinical trials to prove efficacy in women with breast cancer who are to receive taxane chemotherapy in the absence of metastatic disease. Imagine this mentality—the drug works in metastatic disease, but now the company should spend more millions of dollars to show that it works in less extensive disease. Can we afford this blatant waste of life and healthcare dollars?

Xinlay™ (atrasentan) has been shown to double the time to progression of disease in prostate cancer patients, compared with placebo, but the FDA has still not approved it.47,48 We need to expand patient access to the countless promising drugs and technologies that have been determined to be safe, but have not yet been approved, or that are destined to meet their demise without ever receiving the touch of the FDA’s golden scepter.

An Interim Proposal for FDA Reform

Cancer patients should have access to drugs and technologies that have shown minimal toxicity, but that have shown efficacy based on peer-reviewed literature and formal presentations at recognized medical conferences. Such drugs and/or technologies could be granted a “semi-approval status” by the FDA with the implication that at some future date they could be granted full FDA approval.

The conditions for availability of such drugs and technologies would involve:

1. Patient access to drugs with evidence of significant activity and safety.

2. Pharmaceutical company ability to charge for agents without jeopardizing economic solvency, while agreeing to cost reductions of agents resulting from semi-approval status.

3. Ongoing collection of complete and accurate data by designated physicians that is submitted for review.

4. Physician reimbursement for services in delivering therapies.

5. Legal counsel preparing documents to eliminate risk of litigious actions. Patients wanting access to agents must assume risks and waive access to liability.

6. Creating task forces consisting of scientists, consumers, and other relevant individuals involved in a quarterly review process of clinical data.

We believe that access to state-of-the-art medicine is the birthright of all individuals. Included in that birthright is the option to use whatever alternative medicine or innovative medical procedure or pharmaceutical agent seems prudent, as it becomes available, without suppression by a politicized and bureaucratic governmental agency.

There is a revolution brewing, and FDA reform is the target. Every individual patient and all of those who are stakeholders—and that’s all of us—can be part of the solution, rather than passively accepting the status quo and remaining part of the problem. A government responsive to the needs of the people can’t help but recognize the legions of cancer patients and their loved ones who are taking to the streets in support of the approval of Provenge®, carrying signs and demanding that their voices be heard.49,50 Other campaigns—such as the “Raise A Voice” movement being conducted by prostate cancer patients who are running out of time—are waging war on their cancer by confronting the myopic agency that prevents them from gaining access to the drugs and procedures that can prolong the length and improve the quality of their lives.51

We are all a part of this struggle. This is our government, and these are our lives and the lives of our loved ones that are being jeopardized by an agency that seems increasingly inept and ripe for reform. We need to act now, before our very lives ebb away, as do those of thousands of cancer patients who are dying every day in the FDA’s waiting room.

What YOU can do! On page 13 of this issue of Life Extension magazine, there is a description of the legislative action you can take now to stop these needless cancer deaths.

The Life Extension Foundation has set up an easy-to-use website that lets you type in your zip code and then easily email your Representative and two Senators a letter urging them to support legislation that would provide seriously ill patients with quicker access to potential life-saving medications.

We ask every Life Extension supporter to spend only a few minutes to let their members of Congress know how critical it is to tear down the bureaucratic walls that are causing tens of thousands of Americans to die needlessly each year.

To log on to this special legislative website immediately, go to: www.lef.org/lac

If you have any questions or wish to discuss any aspect of this article, please call one of our Health Advisors at 1-800 226-2370.

Products
Malignancy
Results of Trials

Provenge®

Prostate cancer (PC)

Trial D9901: At 3 years, the Provenge® group had three times the survival rate vs. placebo group (34% survival versus 11%). The chance of this occurring simply by accident is 0.5%.52 Update of D9901 Trial: Average prostate cancer specific survival was 35.2 months for Provenge® vs. 23.5 months for placebo.53 D9905: 72% of patients receiving Provenge® were able to prolong their PSA doubling times by 62% [4.9 to 7.9 mos] (p=0.09).54

Phenoxodiol

Ovarian cancer

Study involved heavily pretreated patients who had an average of 5 prior chemotherapy regimens (range 2-10). On phenoxodiol, 5 of 13 patients were stable and still alive approximately 9.5 months after treatment.55

Phenoxodiol

Prostate cancer (PC)

This study involved late-stage androgen-independent PC. In the 200 mg three times per day and the 400 mg three times per day groups, 2 of 4 and 3 of 4 patients, respectively, had no evidence of disease progression at 6 months. The PSA levels in these 5 patients at 6 months were at or below the PSA baseline levels. No toxicity from phenoxodiol was seen.56,57

Junovan™ (L-MTP-PE)

Osteosarcoma

There was a relative reduction in risk of recurrence of 25% and a relative reduction in the risk of death of 30%.58

Genasense® (oblimersen sodium)

Melanoma

In a randomized study of 771 patients, Genasense® plus dacarbazine chemotherapy showed an improved survival trend (median, 9.0 vs. 7.8 months; p=.077) with 2-years of minimum follow-up. Increases in progression-free survival (median, 2.6 vs. 1.6 months; p<.001), overall response (13.5% vs. 7.5%; p=".007)," complete response (2.8% vs. 0.8%), and durable response (7.3% vs. 3.6%; p=".03)" were seen. Genasense® significantly increased survival if baseline serum LDH was not elevated (median overall survival, 11.4 vs. 9.7 months; p=".02).59"

Genasense® (oblimersen sodium)

Chronic lymphocytic leukemia (CLL)

Patients were randomly assigned to 28-day cycles of fludarabine (25 mg/m2/d) plus cyclophosphamide (250 mg/m2/d) administered i.v. for 3 days with or without oblimersen (3 mg/kg/d as a 7-day continuous i.v. infusion). In 241 patients, complete remission (CR) & partial remission (PR) occurred in 20 of 120 (17%) patients in oblimersen group versus eight of 121 (7%) patients in chemotherapy-only group (p=.025). Achievement of CR/PR was correlated with an extended time to progression and survival (p<.0001). In patients who remained sensitive to fludarabine, oblimersen was associated with a four-fold increase in the CR/PR rate and a significant survival benefit (p= ".05).35"

Xinlay™ (atrasentan)

Prostate cancer

Atrasentan significantly delayed time to clinical progression and PSA progression. Comparing placebo, 2.5 mg, and 10 mg atrasentan, the median time to clinical progression was 129, 184 (p=0.035), and 196 (p=0.021) days, respectively. Median time to PSA progression was 71, 134 (p=0.13), and 155 (p=0.022) days, respectively.60,61

Abraxane® (nab-paclitaxel)

Breast cancer

Abraxane® demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel (Taxol®) in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes such as Taxol® and Taxotere® make the novel albumin-bound paclitaxel (Abraxane®) an important advance in the treatment of metastatic breast cancer.62 Using Abraxane®, high response rates occur even in women with progressive cancer despite Taxol® or Taxotere® therapy. Abraxane® is currently approved for metastatic breast cancer, but was rejected by the FDA for earlier stages of breast cancer.

Combidex® (ferumoxtran-10)

Prostate cancer, other cancers that spread to lymph nodes

Combidex® has shown accuracy rates of 95% in the detection of nodal metastases as small as 5 mm.63 Contrast this with low sensitivity of 47% of CT scans and detection rate of 0.5% using bone scans in prostate cancer. The latter two insensitive imaging studies, in the evaluation of prostate cancer alone, result in an annual expenditure of $500 million worldwide.

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