My Concerns about Provenge Vaccine

This year, Provenge (sipuleucel-T), a form of immunotherapy using some of a patient’s own white blood cells, was approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic prostate cancer that is no longer responding to hormonal therapy.

A recommended course of therapy is 3 doses administered intravenously over a period of approximately 60 minutes at approximately 2-week intervals.

The active ingredients consist of the patient’s own mononuclear white blood cells that have been removed by a process similar to donating blood, called leukapheresis, three days before the treatment infusion date.

These cells are then cultured with a genetically engineered human protein, called PAP_GM-CSF, consisting of prostatic acid phosphatase (normally contained in prostate cancer cells) linked to granulocyte-macrophage colony stimulating factor, an immune cell activator.

During culture, the protein antigen – a substance that causes the immune system to produce antibodies and cancer-killing immune cells – can bind to and be processed by antigen-processing cells into smaller protein fragments.

This antigen-immune activator cocktail is designed to target the patient’s immune response to prostate cancer cells containing prostatic acid phosphatase.

Fairly severe flu-like acute infusion reactions have been observed in about 25% of patients. To minimize or avoid these symptoms, an antihistamine and anti-inflammatory drug is recommended 30 minutes before treatment.

The effectiveness of Provenge was evaluated in three similar multicenter clinical trials. Provenge did not significantly prevent the cancer from progression but was associated with about 4 months longer survival – about 1.5 months longer than can be achieved by standard chemotherapy with docetaxel (Taxotere).

Skepticism about the value of Provenge is justified because although the initial studies showed a survival benefit, they did not demonstrate a delayed progression of cancer.

Usually, both benefits are seen in proven cancer therapies. The reasons for this disconnect remain a matter of speculation.

Now that Provenge has been approved, another concern is capacity, because Dendreon Corporation, the manufacturer, does not presently have the facilities to handle the demand.

Dendreon intends to make Provenge available through about 50 centers, all of which were approved clinical trial sites. The company plans to expand its existing manufacturing facility in New Jersey and is building facilities in Los Angeles and Atlanta, scheduled to be complete in mid-2011.

Another concern is cost. Although some private insurers and Medicare insurance contractors are already paying for Provenge, Medicare may take a year to decide about national coverage. All Medicare contractors must adhere to a final decision, and most private insurers will probably follow suit.

A course of treatment has been estimated to cost $93,000. Even if Provenge is covered, many patients will need assistance to cover the co-pays charged by many plans.

I am concerned that information to the public has presented an unjustifiably optimistic view of vaccine therapy for prostate cancer and unrealistically suggests that Provenge will usher in a new era of cancer treatment more effective than surgery, radiation, or hormonal therapy.

In addition, from the data I have seen on Provenge, I am skeptical that it will add materially to the treatment of patients with advanced-stage prostate cancer.