Researchers at Cedars-Sinai Medical Center report
that very low doses of a potent new bisphosphonate, zoledronic acid (Zometa), reduces the complications arising from multiple
myeloma and breast cancer that have metastasized to the bone. The study,
published in Cancer (91:1191-1200), shows that a 5-minute infusion of
zoledronic acid has the same effect as much higher doses of pamidronate
(Aredia), a similar therapy administered over a 2-hour period.
"Not only was zoledronic acid effective in much lower
doses, but we could give the drug to patients over a much shorter time than we
could with pamidronate," said James Berenson, md, director of the Multiple
Myeloma and Bone Metastases Program at Cedars-Sinai Medical Center. "This
means a more potent and convenient alternative for patients battling the
debilitating effects of cancers that have spread to the bone."
Bisphosphonates vs Radiation
Both zoledronic acid and pamidronate are types of
bisphosphonatescompounds that work by slowing the production of cells that
destroy bone. Under normal conditions, cells called osteoclasts remove old bone,
after which cells called osteoblasts can begin building new bone. But when
cancer spreads, the normal balance of the cells is disturbed and the osteoclasts
are more active, causing bone fractures, pain, spinal cord compression, and
Radiation therapy is often required to help alleviate these
complications. However, radiation causes side effects such as extreme fatigue
and lower levels of infection-fighting white blood cells. Alternatively,
bisphosphonates cause fewer and less serious side effects, which include
flu-like symptoms and some bone pain, and can be given safely to patients
receiving simultaneous chemotherapy or hormonal therapy. Thus, pamidronate and
other bisphosphonates have been increasingly used for skeletal complications due
to cancers that have spread.
Zoledronic Acid vs Pamidronate
Earlier studies by Dr. Berenson and his colleagues have already
shown that a lower dose of zoledronic acid is safe and reduces the indicators of
bone loss, such as excess calcium in patients whose cancer had spread to the
bone. The purpose of this current study is to determine whether zoledronic acid
is as effective as pamidronate in reducing bone complications.
Investigators evaluated 280 patients with bone metastases due to
metastatic breast cancer or multiple myeloma. Those who received zoledronic acid
were split into three groups by dosage, either 0.4, 2.0, or 4.0 mg, infused over
5 minutes. Another group of patients received 90 mg of pamidronate infused over
2 hours. Both drugs were administered once a month for 10 months. The treatment
was considered effective if fewer than 30% of the group required radiation
therapy to the bone. Although some patients discontinued treatment due to death
or complications from their cancer, approximately 76% of all patients given
zoledronic acid and 82% in the pamidronate group completed at least 6 months of
The results show that zoledronic acid was as effective as the
much higher dose of pamidronate in reducing the need for radiation to bone. In
the 2.0-mg and 4.0-mg zoledronic acid groups respectively, 19% and 21% of
patients received radiation; 18% of patients in the pamidronate arm also
received radiation. The lowest dose (0.4 mg) of zoledronic acid was found to be
significantly less effective than either the higher doses of zoledronic acid or
pamidronate, with 24% receiving radiation.
"We found that the proportion of patients receiving
radiation to bone in the zoledronic acid group was very comparable to those
patients receiving the much higher dose of pamidronate," added Dr.
Berenson. "Complications such as fractures, spinal cord compression…and
hypercalcemia occurred less frequently in the patients receiving the higher
doses of zoledronic acid."
In addition, investigators found that the higher doses of
zoledronic acid increased bone density in the spine by almost 10%.
"Zoledronic acid may provide a much more convenient and effective therapy
for overcoming the skeletal complications of bone metastases," said Dr.
Currently, Dr. Berenson and his team are conducting phase III
clinical trials to further compare the effects of zoledronic acid and
pamidronate in bone metastases.