Almost all patients who are receiving the EGFR inhibitor cetuximab (Erbitux) will have decreasing levels of magnesium (hypomagnesemia). 

To study this side effect, Belgian researchers measured magnesium levels in the urine and blood of 98 patients receiving EGFR treatments, either as a single drug or in combination with chemotherapy.  97% of them had magnesium levels decrease during treatment.  Controls on only chemotherapy did not have a similar side effect.

Urine testing and a special IV magnesium load test revealed that the kidneys were not reabsorbing magnesium and returning it to the bloodstream.

Led by Prof. Sabine Tejbar, M.D., the team concluded:

EGFR-inhibiting antibodies compromised the renal magnesium retention capacity, leading to hypomagnesemia in most patients. Future studies should address the effects of exposure and target affinity. Our study suggests a pivotal role of the EGFR-signalling pathway in regulating magnesium homoeostasis.

SOURCE:  Tejbar et. al. Lancet Oncology, early online publication April 17, 2007.

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

Leroy Sievers, who is living with metastatic colon cancer, is featured on National Public Radio’s call-in program Talk of the Nation, Monday, April 16th.  Live shows are carried by NPR stations at 2 p.m. and 3 p.m. Eastern time.  An audio webcast will be available on the Talk of the Nation site about  6 p.m. that day.

The show will be broadcast from Washington D.C. before a live audience.  People who want to be part of the audience should contact NPR at talk@npr.org.

Sievers writes an insightful daily blog  for NPR — My Cancer — where he chronicles his life dealing with colon cancer that has spread to his brain. 

Talking about the language of cancer, he writes,

Maybe the best thing to say is that we all just “deal with it.” Some days that involves fighting; other days, coping. Some days we don’t win, some days it’s a struggle to do the smallest thing and other days the battle swings our way. We all just deal with it in our own ways and do the best we can on any given day.

Sievers has won 12 national news Emmys and two Peabody awards.  He worked for ABC News Nightline for 14 years, four years as executive producers.  As a correspondent he covered more than a dozen wars, accompanying Ted Koppel during the invasion of Iraq.

His blog has many followers, both cancer patients and family members, who write often to comment on what he says each day.

Leptin, a hormone that is released from fat cells, caused an increase in the development of colon cancer cells in three colon cancer cell lines.  When the cell lines were treated with leptin the number of cells increased and fewer cells died.

Leptin may provide the connection between obesity and increased risk for colon cancer. 

Researchers at the University of California at San Diego not only discovered the effect of leptin on colon cancer cells, they studied signalling pathways by which it appears to act.  When the treated the cells with inhibitors of MAPK and PI3-K signalling, fewer new cancer cells developed and cells died.

This may provide a target for a drug that could treat colon cancer.

M.R. Hoda and team at UCSD concluded:

Chronic increases in leptin concentration may enhance the growth of colonic cancers via MAPK and PI3-K pathways. These effects of leptin could provide a link between obesity and colonic cancer, and may represent a target for anticancer drug development.

SOURCE: Hoda et. al., British Journal of Surgery, Volume 94, issue 3 pages 346-354, March 2007.

An article about the study from BBC News.

Obesity is a major risk factor for colorectal cancer.  And studies show that eating fruit and vegetables also reduce colon and rectal cancer risk.

But an annual study conducted by the Centers for Disease Control found that men and women of all racial backgrounds are failing to get enough exercise and eat at least five servings of fruit or vegetables every day.

CDC analysts reviewed self-reported data from the 2005 Behavioral Risk Factor Surveillance System (BRFSS), a telephone survey of nearly 318,000 Americans. 

To find out if an individual was eating five or more servings of fruits or vegetables each day they asked:

How often do you drink fruit juices such as orange, grapefruit, or tomato?” “Not counting juice, how often do you eat fruit?” “How often do you eat green salad?” “How often do you eat potatoes, not including French fries, fried potatoes, or potato chips?” “How often do you eat carrots?” and “Not counting carrots, potatoes, or salad, how many servings of vegetables do you usually eat?”

They also asked about physical activity:

To measure physical activity, respondents were asked how often they engaged in physical activities of moderate intensity (i.e., brisk walking, bicycling, vacuuming, gardening, or anything else that causes small increases in breathing or heart rate) and vigorous intensity (i.e., running, aerobics, heavy yard work, or anything else that causes large increases in breathing or heart rate) for at least 10 minutes at a time in a usual week. Respondents were classified as being regularly active if they reported engaging in moderate-intensity activity at least 30 minutes per day, 5 or more days per week, or vigorous-intensity activity at least 20 minutes per day, 3 or more days per week.

They then combined the two responses to identify people who both ate fruits and vegetables and exercised regularly and another group who did neither. Results were classified by sex and racial background.

Percentages of study responders who combined both healthy diet and exercise were:

• Non-Hispanic white men — 12.6 percent
• Men of other races — 16.5 percent
• Non-Hispanic black women — 12.6%
• Hispanic women — 14.8 percent
• White women — 17.4 percent

The study concluded

These results underscore the need to promote diets high in fruits and vegetables and regular physical activity among all populations in the United States and among racial and ethnic minority communities in particular.

SOURCE: J. Kruger et. al., Centers of Disease Control, Morbidity and Mortality Weekly Report, Volume 56, Number 13. April 6, 2007.