OncoLog, Volume 59, Number 10, October 2014 Page: 4
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Neoadjuvant Targeted Therapy May Offer Mul
for Patients with Locally Advanced Renal CaiBy Kathryn L. Hale
Despite definitive treatment with nephrec-
tomy, locally advanced renal cancer recurs in
20%-30% of patients, substantially reducing
their chance for long-term survival. To prevent
such recurrences and prolong survival, urologic
oncologists are studying the integration of
targeted molecular therapies with surgical
treatments.Patients with metastatic disease
surviving longer
The new approaches for locally ad-
vanced renal cancers have emerged from
what has been learned by treating met-
astatic disease.
Because conventional cytotoxic
therapies are not effective against
renal cancers, the recommended treat-
ment for locally advanced renal can-
cers is usually nephrectomy. For meta-
static renal cancers, however, surgery
is indicated in only a few well-selected
patients; and most patients with meta-
static disease had few options until the
introduction of targeted therapies less
than a decade ago.
Targeted therapies fight cancer by
inhibiting proteins such as vascular en-
dothelial growth factor receptors and
tyrosine kinases that stimulate tumor
angiogenesis or promote tumor growth
in other ways.
Since the introduction of these
agents for the treatment of renal can-
cer, said Christopher Wood, M.D.,
a professor in the Department of Ur-
ology at The University of Texas MD
Anderson Cancer Center, "Many pa-
tients with metastatic disease are liv-
ing significantly longer than expected;
the overall survival time has more
than doubled. Some of these patients
are now living for years, whereas be-
fore the median survival was less than
1 year."Targeted therapy for locally
advanced disease
The promising results of targeted
therapy in patients with metastatic
renal cancer prompted urologic oncol-
ogists to ask whether targeted agents
could be effective in prolonging sur-
vival in patients with nonmetastatic
disease. For these patients, surgery in
the form of partial or radical nephrecto-
my offers a chance at a cure; however,
the disease may recur after surgery, sig-
nificantly shortening survival.
The first trials of the targeted agents
in nonmetastatic renal cancer looked
at their effectiveness in the adjuvant
therapy setting (i.e., after resection)
with the goal of decreasing risk of re-
currence. The final results of these tri-
als have not yet been reported, but the
investigators agree on one point: the
targeted agents were not well tolerated
after surgery, especially for a prolonged
duration.
Dr. Wood said, "Many patients were
not able to tolerate the toxic effects
while recovering from surgery and had
to take a lower dose or drop out alto-
gether. Others were not willing to toler-
ate the agents' toxic effects in the face
of a recurrence risk of only 20%-30%."
These findings led the researchers
to test the agents in the neoadjuvant
therapy setting (i.e., before surgery) in
patients whose tumors were considered
resectable.The neoadjuvant therapy approach
in these patients has several potential
benefits: elimination of micrometastatic
disease, which may decrease the chance
of recurrence and prolong survival;
shrinking of the primary tumor, which
might allow a change in the surgical
approach to nephron-sparing partial
nephrectomy rather than radical neph-
rectomy or from open surgery to a mini-
mally invasive approach; and conver-
sion of an unresectable tumor to a re-
sectable one.
One risk of the neoadjuvant therapy
approach is that the toxicity of the tar-
geted agent might debilitate patients to
the extent that surgery would be more
difficult for them. Also, because many
targeted agents are antiangiogenic, they
may interfere with postoperative wound
healing. This is a formidable problem if
surgery is "sandwiched" between two
periods of targeted therapy.
In the early neoadjuvant therapy
trials, patients with locally advanced
or metastatic renal cancer were treated
with a targeted agent, underwent sur-
gery, and then resumed targeted therapy
as soon as possible afterward. The goal
of these early trials was to determine
whether this approach was safe and
effective in preventing recurrence.
Dr. Wood said, "These trials showed
that the agents generally were better
tolerated as neoadjuvant therapy than
as adjuvant therapy. They also showed
that the tumor's response to the therapy
was a good litmus test for whether the
patient was likely to benefit from sur-
gery.
Tumors that progressed while the
patient was receiving targeted therapy
were considered unlikely to be curable
by surgery, while tumors that remained
stable or, better yet, shrunk were consid-
ered very likely to be curable by surgery.
Neoadjuvant axitinib shrinks
locally advanced tumors
While the results of the early trials
of neoadjuvant targeted therapy for4 OncoLog October 2014
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University of Texas M.D. Anderson Cancer Center. OncoLog, Volume 59, Number 10, October 2014, periodical, October 2014; Houston, Texas. (https://texashistory.unt.edu/ark:/67531/metapth639809/m1/4/: accessed May 7, 2024), University of North Texas Libraries, The Portal to Texas History, https://texashistory.unt.edu; crediting UNT Libraries Government Documents Department.