TEL HASHOMER, IsraelIsraeli investigators report that a new technique
delivering waves of paclitaxel (Taxol) directly into recurrent brain tumors
has produced significant responses in patients with recurrent glioblastoma
(ASCO abstract 316).
Five of 12 patients treated in a phase I study had a complete response,
according to M. Raphael Pfeffer, MD, director of radiation oncology at Chaim
Sheba Medical Center in Tel Hashomer, Israel. One patient had already
survived 52 weeks, and another was 36 weeks out from the experimental
treatment. The Israeli team, led by Zvi Ram, MD, is planning a large
multicenter trial with investigators in Europe and the United States, Dr.
Pfeffer said, and several international studies will test the technique with
The new drug delivery method, called convection-enhanced delivery (CED),
is used in conjunction with diffusion-weighted magnetic resonance imaging
(MRI), as described at last year’s annual meeting of the American Society
of Clinical Oncology. CED pumps the drug
through a catheter that has been inserted directly into the tumor. Delivery
is in small pulses, rather than a continuous flow, and the researchers are
able to monitor response inside the tumor in real-time by the
diffusion-weighted MRI, which is sensitive to the speed of water molecules.
"Just like a wave propagates across a pond, the drug will propagate
across the tumor, and therefore it gets well distributed in the tumor,"
Dr. Pfeffer said.
Although paclitaxel has been shown to be effective against glioblastoma
in vitro, the drug does not cross the blood brain barrier. Previous attempts
to deliver the drug directly into a tumor were unsuccessful, according to
Dr. Pfeffer, because the drug pooled around the catheter. By delivering the
drug in small pulses at a rate is of 5 µL/min, CED "makes a wave of
fluid that oozes throughout the tumor," Dr. Pfeffer told ONI.
Dose Dropped 50%
The first three patients started treatment at a dose of 7 mg of
paclitaxel per day for 5 days. Two developed peri-tumoral edema, somnolence,
and chemical meningitis that lasted 4 to 5 days. The researchers dropped the
dose by 50% to 3.5 mg of paclitaxel per day for up to 5 days (a total dose
of 17.5 mg), and found the subsequent patients responded as well but without
these side effects.