Company Dendreon
Information www.provenge.com
Provenge is the first FDA-approved personalized immune-boosting compound for the treatment of cancer that was shown to provide a survival benefit for patients. In clinical trials, the Provenge group lived significantly longer and had a 22.5% reduction in the risk of death compared with men in the control group. As a result, questions abound regarding this treatment. In this section, we’ll try to provide answers about this new therapy.
Dosage As a quick overview, the Provenge treatment is accomplished by removing a small quantity of your immune cells at a blood bank or medical center. (More explanation of this process follows later in this chapter.) Those cells are then sent to the company’s manufacturing facility. After two or three days, the patient returns to a doctor’s office or medical center trained in this treatment to receive an infusion of the boosted cells. The entire Provenge procedure is repeated three times over a period of approximately four weeks.
Question: Who qualifies to get Provenge right now?
Answer: The FDA has approved Provenge for men with metastatic castrate-resistant (hormone refractory) prostate cancer that is asymptomatic (without symptoms) or with minimal symptoms. Basically, if a patient’s PSA rises 3 consecutive times on LHRH or androgen-deprivation therapy (ADT), and the doctor finds metastatic disease (bone metastasis, for example, using a bone scan), then that patient potentially qualifies.
Question: Do I have to remain on my hormone therapy (LHRH treatment) when I receive Provenge?
Answer: In the clinical trials, men stayed on their hormone therapy, so it would seem wise to do the same. However, that decision will be made in consultation with your doctor.
As discussed earlier, some believe that hormone therapy gives a slight immune boost itself in the way that it treats the disease, but others do not believe this boost exists. Those who believe a boost exists point to an increased immune reaction found at some tumor sites in men who had their prostate removed and were on LHRH treatment. Also, the thymus, a gland in the neck that helps to mature and perhaps produce some immune cells, shrinks with age and becomes less functional. However, researchers have noticed that in some patients the thymus can actually begin to grow again and become more active during hormone therapy. Of course, the low testosterone level produces many side effects, but it is important to consider that all men who were treated in the Provenge FDA-approved clinical trial had castrate testosterone levels during the trial.
Advantages The treatment is simple, has a low rate of side effects, and gives men a new option before (or even after) chemotherapy. The FDA has also offered flexibility in who receives it, making it available to men without symptoms or with minimal symptoms of HRPC who have metastatic disease.
The catch It’s expensive. Total cost of treatment is in excess of $90,000. However, insurance, including Medicare, will cover most of the cost.
What else do I need to know? There are numerous medical centers trained to administer the treatment right now, and more sites are being added. Both oncologists and urologists can provide Provenge.
Question: Can you walk me through the actual Provenge treatment process?
Answer: The treatment process with Provenge takes place in three steps. In the first step, the leukapheresis process, blood cells are withdrawn from a patient’s arm. The blood goes through a machine that separates the white blood cells (immune cells) from the rest of the blood and collects them. The patient’s blood, minus those cells, is returned to his other arm. In step two, the patient’s white blood cells are sent to a facility where they are combined with a protein that is unique to prostate cancer cells. That protein helps to produce an immune response to the patient’s cancer. In step 3, the immune-boosted cells are returned to the patient to combat his cancer. This process is repeated for three cycles, each approximately two weeks apart.
THE PROVENGE PROCESS
The precise mechanism of action of PROVENGE is not known.
Question: What happens if a treatment is missed or delayed?
Answer: Once step 1 is completed, it is important to stay on schedule through step 3 unless there is a true emergency situation. If the infusion step is delayed, then the cells will not be usable and the leukapheresis would need to be repeated, adding additional cost in the case of patient delays not related to patient health. The boosting process was really the key treatment step that significantly increased life expectancy in men with HRPC.
It is less critical that the treatments occur at 2-week intervals. Each time a treatment occurs, the patient receives an immune response that lasts for a variable but lengthy time period. The schedule developed is believed to be optimal, but patients will still receive a benefit from delayed treatments if the patient’s situation requires the delay.
A good analogy for the immune-boosting process would be a military one. The patient’s immune cells are basically immature inexperienced soldiers, and some are removed from the war (the body) in step 1. The immune-cell soldiers are sent to boot camp (the manufacturing facility). Within a few days, they are turned into experienced, smarter, and more fit military veterans, capable of doing battle with the cancer (step 2). Step 3 returns them to the battlefield (the infusion process) to fight the enemy, cancer.
Question: Can you explain more about the negatives associated with this treatment, other than the cost? What were some of the most common side effects, how serious are they, and how long did they last?
Answer: The most common side effects that occur within one day after step 3 are (as reported by the New England Journal of Medicine):
| Chills | 51 percent of the individuals |
| Fever | 23 percent |
| Fatigue | 16 percent |
| Nausea | 14 percent |
| Headache | 11 percent |
Most of these flu-like side effects are temporary and are common with immune-related procedures. The side effects generally end within a day or two after the procedure. There were very few cases of “dropouts” or patients who discontinued the entire treatment because of side effects. In fact, in fewer than 1 percent of cases were any side effects serious enough to stop a patient from receiving all 3 treatments.
Question: Are older patients (65 years and older) more likely to experience a side effect from Provenge as compared to younger patients?
Answer: No. There were no differences in safety between older and younger men. The latest Provenge clinical trial included men as young as 40 years old and as old as 91 years old, with the median age in the study being 71 years old.
Since this treatment works in a new and different way, it is worth considering how doctors know that patients are responding to Provenge. Only in a minority of patients is there a PSA drop or a change in an imaging test, such as a bone scan. The FDA no longer bases its evaluation of response in clinical trials for men with HRPC on a change in PSA, but rather on the extension of life. This FDA evaluation change makes a great deal of sense due to the fact that therapies may not change PSA, but may still extend life. This is what was demonstrated in the Provenge clinical trials. Provenge extended survival in patients with HRPC significantly more than the control group and therefore was