A 50-year-old method for delivering chemotherapy
directly into the abdomen is making a comeback as
investigators have found that it increases survival —
by more than a year — in some women with advanced
ovarian cancer.
Results from a seven-year study of more than 400
patients nationwide are published in the Jan. 5 issue of
the New England Journal of Medicine.
Investigators randomly grouped women with newly
diagnosed stage III ovarian cancer into two categories:
those who would get all chemotherapy intravenously and
those who would get chemotherapy both intravenously and
through a catheter inserted directly into the abdomen.
"The catheter allows us to bathe the entire abdominal
area with a high concentration of chemotherapy for a long
period of time, which appears to be better at destroying
lingering cancer cells," said Deborah Armstrong, associate
professor at the
Johns
Hopkins Kimmel Cancer Center and principal investigator
for the study, which was conducted by the Gynecologic
Oncology Group. While the main site for ovarian cancer
spread is the abdominal area, Armstrong said that the
intravenous round of chemotherapy is needed to catch cancer
cells that may have spread outside the abdomen.
Overall survival for 205 patients receiving abdominal
(or intraperitoneal) chemotherapy in the study was an
average of 65.6 months, a 25 percent improvement over the
intravenous-only group of 210 patients, whose average was
49.7 months. Similarly, relapse-free survival for those
receiving intraperitoneal chemo was 23.8 months compared
with 18.3 months for the intravenous-alone group, a 20
percent improvement.
"This is a significant improvement in survival for
women with this disease, which is most often diagnosed at
an advanced stage," Armstrong said.
Side effects, such as suppressed blood counts and
neurological problems, were significantly worse for the
group receiving intraperitoneal, or IP, chemotherapy. They
reported poorer quality of life during their treatment.
However, investigators noted that one year later, patients
in the IP group were on par with those getting only
intravenous chemo. Nine patients died due to complications
of the treatments, five from receiving IP chemotherapy and
four from intravenous.
With these study results, the team of investigators,
supported by the national Gynecologic Oncology Group, now
can recommend IP therapy as the new standard for many women
with ovarian cancer. According to Armstrong, many
institutions have already adopted this practice.
Armstrong believes that some clinicians might be
deterred by cost and lack of familiarity with IP. "We
haven't done a cost analysis, but we expect IP therapy to
be more expensive than intravenous [due to] more drug and
more staff time," she said.
Patients with adhesions, surgical complications or
poor kidney function, and those who have had the left side
of their colon removed during surgery, are not ideal
candidates for IP therapy.
It also is not clear whether the procedure has any
benefit for recurrent disease or for patients with large
amounts of residual disease after surgery.
Robert Bristow, director of the
Johns Hopkins
Ovarian Cancer Center, said, "The first and most
important step is good surgery. If you don't start with a
surgeon specializing in gynecologic oncology who can
effectively remove most of the tumor, then intraperitoneal
chemotherapy may not work."
According to Armstrong, fewer than 50 percent of U.S.
women with ovarian cancer seek a gynecologic oncology
specialist for their surgery, despite research showing
better outcomes for this group.
IP chemotherapy was first studied half a century ago
for colon cancer but never gained popularity for ovarian
cancer despite several studies that hinted at survival
benefits. The benefits were overshadowed by the promise of
new chemotherapy drugs such as paclitaxel, one of the chemo
drugs used in Armstrong's study.
The second chemotherapy agent used in the current
study was cisplatin, a drug that most clinicians bypass in
favor of carboplatin, a faster and better-tolerated drug.
But since it does not appear to penetrate tumors as well,
most believe that carboplatin is not currently a drug of
choice for IP therapy.
"Modern dosing techniques may reveal that may not be
true, and we're conducting an early study of IP therapy
with carboplatin," Armstrong said. Some investigators are
also studying ways to add new agents that are highly
specific for cancer cells into the IP regimen.
In addition to Armstrong, authors are Brian Bundy, of
the Gynecologic Oncology Group and Roswell Park Cancer
Institute; Lari Wenzel, University of California at Irvine;
Helen Q. Huang, Gynecologic Oncology Group; Rebecca
Baergen, New York Presbyterian Hospital; Shashikant Lele,
Roswell Park Cancer Institute; Larry J. Copeland, Ohio
State University; Joan L. Walker, University of Oklahoma;
and Robert A. Burger, University of California, Irvine.
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