BY MARK SCHOLZ, MD
Since Xofigo was FDA approved two years ago, the
doctors at Prostate Oncology—Dr. Richard Lam, Dr. Jeffrey Turner and I—have
been avid users. So this seems to be a good
time to provide an informal update of our experience with Xofigo to the present
The clinical trial that led to Xofigo’s approval by
the FDA was a prospective, placebo-controlled study demonstrating improved
survival in Xofigo-treated men compared to men treated with placebo alone. The trial showed a very low incidence of side
effects and good relief for men who were suffering from bone pain.
Xofigo is made out of radium, a radioactive
element. After it is injected into the blood stream it concentrates near the
cancer and delivers a potent dose of radiation.
So after Xofigo is injected into the patient, it travels through the
blood stream and concentrates in the irritated areas of the bone and emits
radiation where the cancer is most active.
Since prostate cancer spreads almost exclusively to bone, an injection
of Xofigo ends up targeting most if not all of the cancer. Radiation consists
of high energy, subatomic particles that blast cellular DNA. Once the DNA of
the cancer cell has been hit, the cell is rendered incapable of reproduction. If you stop cancer reproduction you basically
stop the cancer.
To almost everyone, radiation conjures up
horrible visions of toxicity. Fortunately, bone marrow toxicity is rare in men
because Xofigo emits a different type of radiation, “alpha particles,” rather
than the standard “photon type” of external beam radiation. Alpha particles dissipate
their energy over a very short distance, only a couple of millimeters. External
beam radiation therapy, the type of radiation that has traditionally been
relied on to kill cancer cells in the bone, needs to be used very judiciously
because the radiation is “beamed” through the body to hit the target in the
bone. Typically it causes irreversible damage to the surrounding bone marrow.
Over the last two years at Prostate Oncology,
we have treated over 50 patients with Xofigo.
The treatment has been very well tolerated. Occasionally, we have seen a few patients with
mild diarrhea or nausea that has been easily managed with common medications. Men
experiencing pain from cancer usually see either partial improvement or total
resolution of their pain after one to three of the monthly treatments.
As reported from the original study that
led to FDA approval, even though pain relief occurs and alkaline phosphatase
(ALP) levels in the blood decline, PSA may continue to rise. This “disconnect” between PSA and other clinical
parameters such as pain and ALP can be disconcerting to doctors and patients
alike. The reason that it occurs is
unclear. A similar phenomenon has been observed with another FDA-approved
cancer therapy called Provenge.
Experts hypothesize that the survival
advantage from Xofigo and Provenge is due to a slowing of cancer progression
rather than an actual regression of the cancer. This “slowing” is powerful
enough to extend patients’ lives but insufficiently powerful to consistently
induce a decline in PSA. However, in our
practice at Prostate Oncology notable declines in PSA have been observed in a
few patients treated with Xofigo. One patient
dropped his PSA from 50 down to zero and his PSA still remains at undetectable
levels. Another recent patient has
dropped his PSA from 150 down to 8.
For the patients on Xofigo who have rising
PSA levels, it is logical to consider adding another effective anticancer agent
such as Xtandi, Zytiga or Taxotere. It
is encouraging to know that several studies now show that Xofigo can be safely
combined with these other effective therapies.
Xofigo has been a very welcome addition to
our anticancer armamentarium. The
standard FDA approved protocol consists of a course of monthly treatments
continued for a total of six months.
Further trials are in progress to study the potential advantages of
continuing Xofigo for longer than six months.
Our experience to date suggests that longer therapy would indeed be
advantageous in some instances.