Therapy for Recurrent Glioblastoma Multiforme (GBM)
Shows Promise in Clinical Trial
A number of the world’s leading brain tumor treatment
centers are investigating a new tumor-targeting platform
and rapid drug delivery system designed to treat recurrent
glioblastoma multiforme (GBM), a deadly form of brain
cancer with few current treatment options.
Each year 10,000 Americans are diagnosed with glioblastoma
multiforme. The median survival time after initial detection
is 12 months and 6 months after recurrence. The usual
treatment is surgery, followed by radiation and anti-cancer
chemicals. But unlike solid-mass tumors, glioblastomas
have tiny tentacles that spread into the brain, making
it impossible for a surgeon to remove every bit of the
tumor. The tumor grows back, usually within six months,
and is, for the most part, unresponsive to current drugs.(i)
The GLIADEL® Wafer, which delivers BCNU (or carmustine,
a commonly used chemotherapeutic anti-cancer agent)
directly to the brain tumor resection cavity, is one
of the available therapies for GBM. Up to eight dime-sized
wafers are placed in the space once occupied by the
tumor at the time of resection. The wafers slowly dissolve
over the next two to three weeks, bathing the cells
with BCNU. The GLIADEL® Wafer has been approved
by the Food and Drug Administration (FDA) for the treatment
of recurrent and newly diagnosed GBM. Studies have shown
that GLIADEL® Wafer extends the median survival
by eight weeks.(ii)
The PRECISE trial is a Phase III clinical trial of
NeoPharm’s investigational drug IL13-PE38QQR (cintredekin
besudotox). The purpose of the randomized trial is to
compare the survival of patients with first recurrent
GBM treated with IL13-PE38QQR, with the survival of
patients treated with GLIADEL® Wafer following surgical
tumor resection. Safety and quality of life are also
assessed in the study.(iii)
IL13-PE38QQR is made from a human protein, Interleukin
13 (IL-13), linked to a bacterial toxin, Pseudomonas
exotoxin (PE). Interleukin instructs immune cells to
divide or differentiate. IL-13 receptors are found on
malignant gliomas cells, but not to any measurable degree,
if at all, on healthy brain cells. IL13-PE38QQR is designed
to bind to IL-13 receptors on the tumor like a key fitting
into a lock. The cancer cell latches onto and absorbs
the IL-13 and the attached toxic agent, PE38QQR. As
a result, the cancer cell dies. The toxin is harmless
to healthy cells, which lack IL-13 receptors.(iv)
Because IL13-PE38QQR molecules are too large to pass
through the blood brain barrier, the study drug is infused
directly into the brain tissue surrounding the tumor
resection cavity using convection-enhanced delivery
(CED). This method of treatment involves surgical implantation
of 2-4 catheters in the brain. Pumps are used to infuse
the drug solution slowly into the area surrounding the
tumor resection cavity for a period of 96 hours (four
days).
“The early studies look promising for IL13-PE38QQR,
but the study drug may not work for everyone,”
says Dr. Leonard Cerullo, neurosurgeon and founding
member of Chicago Institute of Neurosurgery and Neuroresearch
(CINN), one of the participating trial sites. “When
it works, it can be very effective.”
Phase I results for IL13-PE38QQR look promising. The
median survival rate for 45 patients with GBM receiving
IL13-PE38QQR almost doubled from 26 weeks to 44 weeks.
Several patients survived for more than three years
including a few without any additional anti-tumor treatment
after IL13-PE38QQR, and the FDA has granted IL13-PE38QQR
rare fast-track designation to accelerate approval.(v)
More than 40 prestigious medical centers worldwide
are participating in the PRECISE trial, including Memorial
Sloan Kettering Cancer Center, Cleveland Clinic, M.D.
Anderson Cancer Center, and CINN at Rush University
Medical Center. Given the advancing PRECISE Phase III
study and the encouraging results of the Phase I studies,
a Phase II study for patients with new diagnosis of
GBM including IL13-PE38QQR, radiation therapy and temozolomide
(Temodar®) is planned for 2006.
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