Oral glutamine reduces oxaliplatin neuropathy in pilot study
While oxaliplatin is effective in colorectal cancer to increase survival time and prevent recurrence, it can cause serious peripheral neuropathy. Tingling, numbness, and pain in hands and feet can interfere with daily functioning and impair quality of life. If it becomes bad enough, doses of oxaliplatin must be reduced or discontinued entirely.
Researchers in Taiwan randomized 86 metastatic colorectal patients being treated with oxaliplatin to receive oral glutamine or not to see if the supplemental protein would reduce neuropathy. Patients were receiving their first treatment for metastatic colon or rectal cancer. Oxaliplatin was combined with leucovorin and bolus 5FU.
Although oxaliplatin does cause a short-term neuropathy in hands, feet, jaw, and larynx which can be triggered by exposure to cold, these symptoms usually get better within a few days of treatment and don’t interfere with further doses of chemotherapy. So instead, the research team focused on long-term peripheral neuropathy in hands and feet which gets worse over time as the dose of oxaliplatin accumulates.
The patients in the glutamine group received 15 grams of levo-glutamine (Sympt-X® manufactured by Baxter Health Care Corporation) twice a day for seven days every two weeks, beginning on the day of the oxaliplatin infusion. To avoid confusion, no patients had potentially protective infusions of calcium and magnesium.
Neurological symptoms and ability to accomplish fine motor activities of daily living such as buttoning buttons and opening jars were assessed at the beginning of therapy and after 2, 4, and 6 cycles of treatment. In some cases more extensive electrophysiological neurological tests were carried out.
There were significantly fewer neurological symptoms in patients who received glutamine than in those who did not.
- After two treatment cycles, 16.7% of the glutamine group experienced grade 1-2 sensory neuropathy compared to 38.6% of the control group.
- After four cycles, 26.2% of the glutamine group had grade 1-2 neuropathy compared to 36.4% of controls.
- Grade 3-4 neuropathy after four cycles was 4.8% in the glutamine group and 18.2% in controls. Grade 3 and 4 neuropathy is associated with pain and loss of normal function.
- Grade 3-4 neuropathy after six cycles was 11.9% versus 31.8% in controls.
- Acute, transient, cold-induced neuropathy was also significantly decreased by glutamine supplements — 33.3% versus 56.8%.
- Interference with activities of daily living was 16.7% with glutamine versus 40.9% of the control group.
However, electrophysiological tests, conducted on 14 members of the glutamine group and 14 controls, did not show a significantly objective difference. The team wrote:
Although glutamine supplementation significantly reduced the incidence of “subjective” neuropathy in these patients, it did not exert a protective effect on the deterioration of electrophysiological tests.
Although patients in the glutamine group required fewer oxaliplatin dose reductions, there was no difference in treatment effectiveness.
- No patients in either group had their cancer get worse (progress) after three treatment cycles.
- After six treatment cycles, about twenty percent of each group had progressing cancer.
- About half of each group responded to treatment with tumor shrinkage.
- Median survival for the glutamine group was 17.3 months versus 18.6 months for controls, not a significant difference.
Overall, the research team, led by Wei-Shu Wang, concluded:
In summary, our data suggest that oral glutamine has a potential neuroprotective effect in MCRC patients treated with oxaliplatin, and may therefore improve the therapeutic index. Larger placebo-controlled, randomized studies are needed to confirm the application of glutamine as a protective agent against oxaliplatin-induced neuropathy.
Glutamine is the most abundant protein in blood and in skeletal muscles. It is available as a nutritional supplement and is sometimes used during exercise and body building to improve performance. It can be reduced in the muscles during stress, cancer, and chemotherapy. Previously it has protected breast cancer patients receiving high doses of Taxol from neuropathy.
SOURCE: Wang et. al. The Oncologist, Vol. 12, No. 3, 312-319, March 2007
WHAT THIS MEANS FOR PATIENTS Although glutamine reduced neuropathy during this pilot study without appearing to effect chemotherapy outcomes, this was a small trial that needs to be confirmed in larger, placebo-controlled randomized clinical studies. Glutamine is available as an over-the-counter nutritional supplement, but patients should not take it without discussing it with their physicians.
This news article was originally posted on April 12th, 2007 and was accurate at the time of publication. Since then, information may have changed or links may now be outdated. Please call our Answer Line 1-877-427-2111 for the latest information, or talk to your doctor before making any medical decisions.
Posted by Kate Murphy on April 12th, 2007
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Dennis L.
April 14, 2007 at 6:54am
This study is potentially very good news. I am a gastroenterologist who initally presented with asymptomatic Stage IV disease and underwent combined colon and liver resection with six months of Folfox 7 (includes oxaloplatin). While experiencing cold intolerance and jaw claudication (transient pain with chewing) it was not until the chemo was completed that I experienced the symptoms of a peripheral sensory neuropathy: numbness, tingling, pain, decreased fine motor skills. While the hand coordination has improved the neuropathic symptoms overall have not despite having completed chemo two years ago; although, in the majority of patients the neuropathy tends to resolve. Any prophylactic measure that could be taken concurrently with the chemo that would allow maintenance of the therapeutic dose is clinically valuable. I am curently taking 100 mg. of Vitamin B6 which has improved the pain (not numbness) somewhat. Overall,I have adopted the philosophy that if neuropathy is the only legacy that I am left with following a diagnosis of Stage IV disease I can readily accept that side effect.
DE
October 3, 2007 at 9:24am
I am a colorectal cancer patient. Originally staged 3 T2, underwent 28 days chemo-radiation with 5FU continous infusion, ending June 1. Had surgery end of July, temp. ileo. and just began Folfox. Downstaged to T2N2. After much research, I am using Glutamine (powder) 10g 3x/day mixed in juice or Gatorade, taking a time release high potency B complex, and using acupuncture. I am also taking Avemar, a wheat germ extract that has been show effective as an adjunct to traditional therapy for colorectal cancer. (Avemar.com)
I will keep this board updated as treatments progress. I had chemo #1 on Monday, 10/1, experienced fatigue (not terrible), minor cold sensitivity (swallowing), and a litte tingling fingers and toes….all better by 2 days later. All anti nausea meds are working. So far, all manageable.