Immune Treatment for PSA-Relapsed Prostate Cancer

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By: Mark Scholz, M.D.
Prostate Oncology Specialists
October 2010

PSA-Relapsed prostate cancer can be effectively controlled with Testosterone Inactivating Pharmaceuticals (TIP). When TIP is started soon after relapse, remissions last an average of 11 years. However, TIP has notable side effects such as low libido, hot flashes, osteoporosis, muscle wasting and weight gain. Quality-of-life is improved and long-term survival is unimpaired by taking treatment holidays—by using TIP intermittently. Maximizing the time off TIP by extending the “holiday” period as much as possible, improves quality-of-life even further.

A number medicines work via the immune system. Even TIP itself has been shown to have an activating effect on the immune system. Provenge®, a new treatment approved by the FDA in 2010, works by harnessing the immune system. Ipilimumab, another new immune medicine that functions by inhibiting the regulatory cells of the immune system—the T-Regulatory cells—is being evaluated in phase III trials in prostate cancer. In addition, a variety of agents such as Leukine®, low-dose cytoxan, and Celebrex® have anticancer effects mediated by the immune system.

The main issue that makes immune therapy attractive is fewer side effects.  Another relevant aspect of immune treatment is that it seems to succeed more frequently when the cancer is less advanced. Both of these characteristics are relevant to men with PSA relapsed prostate cancer on intermittent TIP.  First, TIP effectively kills cancer cells and reduces the amount of cancer in the body. Second, the side effects of TIP can be notable. So if nontoxic agents can keep the cancer in check during the holiday period, quality-of-life is improved. Men can enjoy the return of their normal testosterone levels for a more extended period of time.

In an abstract at ASCO in 2010, Prostate Oncology Specialists published the effect of Leukine, Celebrex and low-dose cytoxan in 24 men without bone metastasis and a PSA doubling time less than 12 months administered during the holiday period after 9-12 months of TIP. For the sake of clarity, in the remainder of this article, the combination of Leukine, Celebrex and cytoxan is referred to as “Immune Therapy.”

The median age and Gleason score for the 24 men was 72 and seven respectively. The median PSA at the start of the Immune Therapy was one. Fourteen of the 24 men on the Immune Therapy had more than a 100% increase in PSA doubling time. In the 14 responders the median doubling time before treatment was five months. The median doubling time while on Immune Therapy was 24 months.

The actual dosages of the medication were Celebrex 200 mg twice a day, cytoxan 500 mg once a month intravenously and Leukine 500 mcg injected subcutaneously three times a week. The most common side effect from the treatment was a red, itchy rash where the Leukine was injected. Three men required 50% dose reduction of Leukine due to muscle aches.

More recently, we have been adding Revlimid® 5 mg daily to the protocol.  The Revlimid is administered 21 days straight and then stopped for a week. In other words the schedule is 21 days on treatment followed by 7 days off.

Overall this combination of medications is well-tolerated.  When the Revlimid is added to the mix we see some increase in the incidence of skin rashes.  If the Revlimid is given continuously, i.e. without a week off each month, low platelet counts often occur.