SAN FRANCISCOGlutamine appears useful in preventing
taxane-induced neuropathies, according to Linda T. Vahdat, MD, assistant
professor of medical oncology at Columbia University’s College of Physicians
& Surgeons in New York City. A short course of oral glutamine given after
high-dose paclitaxel (Taxol) significantly reduced the severity of peripheral
neuropathy compared to prior patients who did not receive glutamine in a pilot
study. Glutamine has also been under study for prevention of gastrointestinal
toxicities associated with camptothecins.
Dr. Vahdat told Oncology News International that glutamine will be studied
further in a randomized, controlled trial of 80 patients with a history of
paclitaxel-induced peripheral neuropathies. This trial is expected to open in
late summer and enroll mainly breast cancer patients. The protocol will differ
from the pilot study in that glutamine or placebo will be given beginning on
the first day of paclitaxel administration, rather than after completion of
paclitaxel, and will continue for 9 weeks.
"Peripheral neuropathy limits the usefulness of many newer
chemotherapeutic agents such as the taxanes," Dr. Vahdat explained.
"In this study we report on the possible successful reduction of
peripheral neuropathy with glutamine administration after high-dose
Patients in the study received a high-dose chemotherapy
protocol, with the first high-dose cycle being paclitaxel at 825 mg/m2
given over 24 hours. All patients had complete neurologic examinations and
nerve conduction studies at baseline and at least 2 weeks after paclitaxel.
The first cohort of patients did not receive glutamine. The
second cohort received glutamine at 10 g po TID for 4 days starting 24 hours
after completion of paclitaxel.
Dr. Vahdat reported on paired evaluations, before and after
receiving paclitaxel, of 33 patients who did not receive glutamine and 12
patients who did. The median interval between the evaluations was 32 days.
Glutamine-treated patients had significantly less peripheral
neuropathy as measured by development of moderate to severe dysesthesias and
numbness in the fingers and toes (P < 0.05). These patients were also
less likely to have transient motor weakness (56% vs 25%, P = 0.04) or
deterioration in gait (85% vs 45%, P = 0.016). Glutamine-treated
patients also reported dramatically less interference with activities of daily
living (85% vs 27%, P = 0.001). Glutamine was associated with a nonsignificant
trend toward a reduced incidence of moderate to severe paresthesias in the
fingers (55% vs 42%) and toes ( 64% vs 50%). All of these toxicities were
reversible over time.
"We suspect that glutamine alters nerve growth factor
levels and that this mediates the neuroprotective effect," Dr. Vahdat