Provenge®

Should Medicare spare no expense in extending the lives of elderly people with incurable advanced cancer? Should cost-effectiveness be taken into consideration when approving a drug that works—sort of—but is extremely expensive?

Such questions are crucial to sustaining our currently unsustainable medical care system. But they were studiously avoided last month when Medicare announced that it would pay for Provenge, the controversial drug/vaccine for advanced prostate cancer. Rationing would, of course, be the outcry, but as someone has already pointed out, “It is irrational to think that we can have a medical care system that avoids rationing.”

It also seems irrational to approve a drug for symptomless cancer when the drug itself has a list of distressing symptoms (side effects), according to the company’s official website. Medicare approval was very specific regarding who should receive Provenge: “Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer.” Translation: this drug is proven effective only for men with minimal or no symptoms of advanced prostate cancer that did not respond to chemical castration, aka androgen deprivation therapy.

Here’s the backstory for Provenge, which has been controversial for over three years. The drug/vaccine costs about $93,000, delivered as three intravenous infusions approximately 2 weeks apart. It has been shown to extend life for about four months compared with a placebo. Another way of putting the same information: In the trial conducted for FDA approval, men with advanced prostate cancer who received no treatment lived a median of about 26 months; the men who received the drug/vaccine lived a median of about 30 months.

High hopes were pinned on Provenge by groups representing men with prostate cancer largely because it is a vaccine. It is not a vaccine for prevention; rather it is a vaccine for men who already have prostate cancer. Provenge stimulates the body’s immune system to resist the disease…at least for a short period of time. The voices of patient advocacy were heard loud and clear three years ago when the FDA decided not to approve Provenge for any stage of prostate cancer because effectiveness was uncertain. The advocacy groups generally wanted blanket approval for Provenge. Researchers and policy makers, on the other hand, know from experience that once a high-profile drug like Provenge is approved, it will be prescribed for earlier stages of prostate cancer. Knowing this is likely to happen, Medicare has issued a statement that Provenge should be prescribed for earlier stages of prostate cancer only in the context of a clinical trial. I think we can count on it being ignored, despite the fact that the evidence supporting Provenge’s use for earlier stages of prostate cancer has been described as “virtually nil”.

The cancer patients’ understandable need for hope and extended survival has become the driving force behind the demand for FDA approval whether the scientific evidence is weak, strong, or non-existent. But does it make sense to demand a blank check for anything the drug companies put on the market? And why would a drug company go back to the lab and come up with a more effective drug when it can make lots of money on one that’s only marginally effective?

Though not a chemotherapy drug, Provenge is emblematic of new cancer drugs with extremely high cost and effectiveness so miniscule that one British blogger wrote, only half in jest: “We doctors will have to start measuring chemotherapy’s effect on survival with stopwatches.”

Can we have a national conversation about these issues that is rational? No, is the obvious answer, but it is worth considering the options before you ever develop a terminal condition. Last summer the New England Journal of Medicine published a study that defies conventional wisdom about aggressive treatment for advanced cancer. It showed people with terminal lung cancer who chose early, palliative care offered by hospice had a better quality of remaining life and, surprisingly, a longer life than those given the standard aggressive treatment at the end of life. Click here

Maryann Napoli, Center for Medical Consumers©

Prostate cancer treatment misused

Androgen deprivation therapy (ADT) is prescribed inappropriately for many men in the early stages of prostate cancer and is associated with an increased risk of cardiovascular disease and diabetes. This was shown in a new study of over 37,000 men treated at the early stages of prostate cancer in the Veterans Healthcare Administration between 2001 and 2005. Published in a recent issue of the Journal of the National Cancer Institute, the study raises questions about informed consent and how much information men are given about ADT beforehand. There is no proof that it can prolong life or help men with low-risk, early-stage disease, yet ADT can cause severe adverse effects because it is drug-induced castration.

The research team led by Nancy L. Keating, MD, Brigham and Women’s Hospital, Boston, found that the high risks of diabetes (25%) and cardiovascular disease (20%) were associated with the gonadotropin-releasing hormone (GnRH) agonists. The drugs, sold under the brand names of Lupron and Zoladex, are injected by a physician or implanted under the skin every few months. No increased risk of diabetes and cardiovascular disease was associated with oral anti-androgen drugs like Euflex and Casodex, which are usuallly given in conjunction with GnRH agonists or, rarely, by themselves.

The increased use of ADT was linked to widespread screening with the PSA (prostate-specific antigen) blood test in a hard-hitting editorial that accompanied the VA study. The author, Peter C. Albertsen, MD, Department of Surgery, University of Connecticut Health Center, Farmington, states that the VA study offers a rare glimpse into the extent of ADT usage. He went on to note that PSA screening has dramatically changed the type of patient newly diagnosed with prostate cancer. “Before the advent of PSA screening, physicians used ADT to relieve symptoms of advanced prostate cancer. Now we use ADT primarily to treat patients with a rising level of PSA.” And most tellingly, Dr. Petersen writes, “We do not know whether these treatments [ADT] have prolonged survival, but [this study] confirms that this approach has the potential for substantial unintended side effects.”

Hot flashes, weakness, fatigue, cognitive impairment, and depression are the “substantial unintended side effects” of ADT, aka chemical castration. The VA study is not the first to link ADT to an increased risk of diabetes and cardiovascular disease, but it shines a light on unproven uses of this drastic therapy. The study shows that ADT is often given as the primary treatment for men with local and regional prostate cancer who have no symptoms of the disease, as well as symptomless men whose post-treatment PSA test show rising levels. The increased use of ADT can be chalked up to the fact that the PSA screening test was introduced in the late 1980s. This is well before the benefit of finding prostate cancer before symptoms appear was proven to reduce a man’s chances of dying from prostate cancer. See results of two recent clinical trials that explored this important question.

Dr. Keating, the lead author of the VA study, was asked to identify the men with prostate cancer for whom the proven benefits of ADT outweigh its considerable risks. “There are proven benefits to ADT for men with symptomatic metastatic prostate cancer in terms of controlling the spread of the disease which causes symptoms such as bone pain and fractures,” answered Dr. Keating in an e-mail, “and [there is] also a survival benefit to ADT when used as adjuvant [additional] therapy for men with high-grade disease, which is localized disease with high-risk features that make it more likely to return after primary treatment [with surgery or radiation therapy].”

And for whom is ADT most likely to be questionable? “The concern is that many men are treated with ADT for indications where there have never been studies showing benefit (e.g., as a primary treatment of prostate cancer and as a preventive against recurrence in those whose PSA levels rise after primary treatment). In these settings, the risks may outweigh any benefits,” answered Dr. Keating. “I think this has become a popular treatment because patients and doctors like the idea of doing something to treat the cancer. But the problem is, it has never been studied, and may have substantial adverse effects.”

So has the PSA screening test saved at least some lives? Apparently not, according to editorialist Dr. Petersen, who compared the current prostate cancer death rate with that of the era when men were not diagnosed with prostate cancer until they noticed symptoms. “Before the widespread use of PSA screening, an American man had an 8.7% lifetime risk of being diagnosed with prostate cancer and 2.5% risk of dying from this disease. By 2005, the lifetime risk of being diagnosed had increased to 17%, whereas the lifetime risk of dying from prostate cancer remained virtually unchanged.”

Maryann Napoli, Center for Medical Consumers(c)