mantle cell lymphoma, in 2006. The drug is highly effective in
patients with multiple myeloma, with its use almost doubling the
five-year survival rate. Many patients, like Congressman M.
Robert Carr, have achieved a durable complete response to the
treatment ( 83).
Bortezomib is a unique drug that blocks the breakdown of proteins,
leading to the disruption of multiple pathways that are necessary
for tumor cell proliferation. Its mode of action is not as precise as
that of drugs that target cancer-driving molecular defects intrinsic
to cancer cells, and as a result it has significant side effects. One
side effect that considerably diminishes the quality of life of many
patients is a condition called peripheral neuropathy, which causes
numbness, loss of sensation and pain in the hands and feet.
Two FDA decisions in 2012 should help reduce this serious adverse
side effect and will increase the number of treatment options
available to patients with multiple myeloma. The first was the July
2012 FDA approval of carfilzomib (Kyprolis) as a new treatment for
multiple myeloma. Like bortezomib, carfilzomib prevents the
breakdown of proteins, but its blocking effects are more sustained
and it can be administered on a schedule that is effective but
significantly reduces peripheral neuropathy ( 84). The second was
the January 2012 FDA approval of a change to the way that
bortezomib can be given to patients. Clinical trial results indicated
that administering bortezomib under the skin, rather than into the
veins, did not diminish treatment effectiveness, but dramatically
reduced suffering related to severe peripheral neuropathy ( 85).
A New Day for Existing Drugs
After performing arduous clinical trials that lead to FDA approval for
a drug, researchers and clinicians continue their endeavors,
seeking to maximize the number of patients who can benefit.
Determining if treatments for certain cancers might benefit other
groups of patients and if a drug’s side effects can be mitigated to
make it tolerable to more people not only improves patient care,
but it also increases the return on prior investments in cancer
research. In the first eight months of 2012, the FDA expanded the
use of three previously approved cancer treatments—pazopanib
(Votrient), everolimus (Afinitor) and, as noted above, bortezomib—
increasing their true clinical worth.
• Employs approximately 6, 100
• Admitted 40,192 inpatients, 2,062 of
which were cancer-related admissions
• Admitted 411,514 outpatients, 82,190
of which were cancer-related
admission in 2011.
Dana-Farber Cancer Institute
• Is the only NCI-designated
comprehensive cancer center in
• Employs 3,763 people.
• Had more than 353,000 adult and
pediatric outpatient clinic visits and
infusions in 2011.
The FDA approved pazopanib for the treatment of metastatic renal
cell carcinoma in October 2009. It targets the VEGF receptor family,
disrupting the growth and stability of the emerging blood and
lymphatic vessel networks that support the cancer’s growth. A
recent large-scale clinical trial showed that pazopanib more than
doubles the time to disease progression in patients with certain
metastatic soft-tissue sarcomas ( 86), a group of cancers that it is
estimated will be newly diagnosed in more than 11,000 Americans
in 2012 ( 3). In light of this, in April 2012, the FDA approved the drug
as a treatment for advanced soft tissue sarcoma, providing new
hope for patients who have seen little change in their treatment
options for decades.
Everolimus targets the key molecule, m TOR, in the m TOR signaling
pathway, which senses energy levels, controls tumor cell viability
and drives cell growth. As a result of various genetic mutations, this
pathway is overactive in several types of cancer, and over the past
few years the FDA has approved everolimus for the treatment of
metastatic renal cell carcinoma, certain pancreatic cancers called
neuroendocrine tumors, and noncancerous brain tumors in patients
with an incurable inherited disease called tuberous sclerosis (see
Table 4, p. 38). Between 25,000 and 40,000 Americans have
tuberous sclerosis, which causes noncancerous tumors to grow in
the brain and many other vital organs ( 87). A recent clinical study
indicated that everolimus reduces the burden of noncancerous
brain tumors in patients with tuberous sclerosis and also
dramatically shrinks their noncancerous kidney tumors, data that
led to the April 2012 FDA approval of everolimus for this condition
( 88). In July 2012, the FDA approved everolimus for the treatment
of women with hormone receptor–positive advanced breast cancer
(see below) after a large-scale trial showed it significantly
prolonged time to disease progression or death ( 89).
Increasing the number of cancer types for which a drug is approved
as a treatment is not a trivial advance. It is one that is significant
for the many patients, their families and their loved ones who have
benefitted from this progress. Numerous studies are underway to
pair other proven cancer treatments with new patient populations,
and these are expected to uncover new ways to enhance and
expand both the clinical value of our knowledge and the return on
prior investments in cancer research.