For patients getting the common FOLFOX chemotherapy for colorectal cancer, many oncologists add intravenous calcium and magnesium, hoping to decrease the neuropathy (nerve damage) associated with oxaliplatin-based drugs.

But this week, experts at the 2013 ASCO meeting (American Society of Clinical Oncology), announced strong evidence that the calcium/magnesium does no good in either preventing or decreasing neuropathy—and it should no longer be part of routine treatment.

Neuropathy affects cancer treatment

Oxaliplatin-based chemotherapy (e.g. FOLFOX, with Eloxatin®) is one of the most commonly used drugs for people having high-risk stage II, or stages III or IV colorectal cancer. But far too often after patients have had many doses of FOLFOX over months, they have to stop this effective treatment because of increasing neuropathy—burning or numbness especially in hands and feet that becomes chronic, even permanent.

Based on two earlier preliminary studies (and biological reasoning), many oncologists began giving calcium and magnesium intravenously a half-hour before and/or after the chemotherapy, in an effort to prevent the nerve damage.

But in results from the first large, randomized trial announced at this week’s ASCO meeting, researchers found absolutely no effect from the calcium/magnesium.

Trial shows no benefit

A multisite trial randomly assigned 350 colon cancer patients receiving FOLFOX into three groups—one receiving the calcium/magnesium before and after chemo; a second receiving a look-alike placebo; and the third group getting calcium/magnesium before chemo and a placebo afterwards.

The symptoms of nerve damage—measured in multiple ways—were no different in any of the three groups of patients.

Also, there were no differences in the average number of days until symptoms became significant, or in the number of patients who had to stop the chemotherapy.

“This study did not demonstrate any activity of IV CaMg [calcium magnesium]…” said lead author Charles Loprinzi from the Mayo Clinic. He noted that when he has asked medical meeting audiences how many use intravenous Ca/Mg, more than half the clinicians present say they do.

“This practice should now be stopped,” he told Medscape Medical News in an interview.

Practice-changing results; lesson learned

The study was called “practice changing,” by Dr. Richard Wilson from Queen’s University Belfast in Northern Ireland, speaking at a “Highlights of the Day” ASCO session.

The lesson learned, Dr. Wilson said, was that the original 2004 French study was not randomized and too small for definitive proof, but raised doctors’ hopes. Another 2011 study by Mayo Clinic’s Dr. Axel Grothey (a Medical Advisory Board member for Fight Colorectal Cancer) also showed promising early results. But Grothey’s study had to be stopped early before it could get enough participants because of concerns (later disproven) from a different ongoing study. Studies have shown that the calcium/magnesium infusion does not cause harm, and does not interfere with other chemotherapy drugs’ effectiveness.

Patient take-away

If you are currently getting chemotherapy based on oxaliplatin (e.g. FOLFOX, CapeOx), ask if you are also getting a calcium/magnesium intravenous infusion. If you are, take some time to discuss your particular case with your doctor—because another lesson we’ve learned is that every individual situation is different.

This is also an excellent example of why you see recommendations for treatment, tests, and diet change over time. Science—and our understanding of cancer—builds step by step, as evidence and lessons are learned from many tests done over time.

For more information: You can ask further questions by email in advance, or live by phone, in the upcoming webinar reviewing ASCO called “What’s New and What’s On the Horizon” on Wed., June 19, at 8-9:30 pm. ET. Click here for more information or to register.

Sources:

• “Phase III randomized, placebo-controlled, double-blind study of intravenous calcium/magnesium…” 2013 ASCO meeting and Journal of Clinical Oncology 31, 2013 (suppl; abstract 3501)
• ‘Stop Using Calcium and Magnesium With Oxaliplatin,” June 3 2013 Medscape News
• Intravenous Calcium and Magnesium…”, Grothey, Feb. 1 2011 Journal of Clinical Oncology

Disclosure: Fight Colorectal Cancer has accepted funding for projects and educational programs from sanofi-aventis in the form of unrestricted educational grants. Fight Colorectal Cancer has ultimate authority over website content. See the Fight Colorectal Cancer Funding Policy and Disclosure.

Recent studies show some promise in understanding chemo-caused neuropathy, and perhaps in using a common medicine to ease the worst symptoms in some people.

Study shows neuropathy relief for some using antidepressant

 A well-designed clinical study has provided the first evidence that the antidepressant Cymbalta® (duloxetine) can provide some patients with significant relief from peripheral neuropathy caused by chemotherapy.

From 20 to 40 percent of cancer patients given neurotoxic chemotherapy–taxanes, platinum-based including Eloxatin® (oxaliplatin), vinca alkaloids, bortezomib–will develop painful peripheral neuropathy (numbness, tingling, burning in hands or feet). If the pain is severe, colorectal cancer patients often have to reduce the dose or stop taking Eloxatin. Even then, this painful condition can persist for months, even years, after chemotherapy is stopped.

Previous studies have found that Cymbalta eases the neuropathy pain caused by diabetes, but this is the first comprehensive trial testing whether Cymbalta could ease neuropathy from chemotherapy. As reported in the April 3, 2013 JAMA (Journal of the American Medical Association), the trial enrolled 220 patients at 8 different cancer centers across the U.S. who still had significant neuropathy (at least 4 on a pain scale of 10) at least 3 months after chemotherapy. (Over half, 129 patients, had taken Eloxatin, mostly for colorectal cancer.) In this randomized, double-blind (neither patients nor clinicians know who’s getting the test drug), crossover trial, one-half the group received Cymbalta for 5 weeks while the others took a placebo, and then the groups switched treatments.

Of those taking Cymbalta, 59% reported at least moderately decreased pain (minimum 1 point on the 10-point scale)—usually within the first week. Among those taking a placebo first, 38% reported decreased relief. Interestingly, Cymbalta-associated pain relief was significant only in feet, not hand, symptoms. Also, 11% of people taking Cymbalta had to stop due to side effects—mostly severe fatigue.

Experts theorize that the antidepressant might help because it reduces the neurotransmitters serotonin and noradrenaline, which deliver pain messages to the brain. The study authors pointed out limitations in this first study: relatively small numbers, the effects measured by patient self-report, and the study only followed patients for 5 weeks on Cymbalta.

However, “This is not just about improving quality of life by decreasing pain, but potentially it’s helping patients live longer because they can get their full chemotherapy treatment,” noted lead author Ellen M. Lavoie Smith, Ph.D., APRN, AOCN, of the University of Michigan Comprehensive Cancer Center.

Another expert not connected to the study, Marie Bakitas, D.NSc., at the University of Alabama at Birmingham School of Nursing, noted that the trial results weren’t surprising, because duloxetine is already being used in clinics. But, she also told Medscape, other treatments such as physical therapy, acupuncture and massage “are often neglected but can be very useful.”

Sources: “Effect of Duloxetine on Pain, Function, and Quality of Life Among Patients With Chemotherapy-Induced Painful Peripheral Neuropathy,” April 3 JAMA Network; “Drug for Depression Mutes Chemo Nerve Pain,”April 2 Medscape; “Antidepressant helps relieve pain from chemotherapy, study finds,” April 2 Univ. of Michigan Health Systems press release.

Searching for genes that could predict peripheral neuropathy

 Mayo Clinic researchers have reported that they’ve found that patients with mutations in  three specific genes were more likely to suffer peripheral neuropathy from chemotherapy.

Currently, doctors have no way to predict who will have the side effect, how severe it will get, nor how long it will last.

At the recent meeting of worldwide cancer researchers (AACR, or American Association of Cancer Researchers), scientists described how they studied more than 20,000 specific genes in 119 patients—over half of whom had developed peripheral neuropathy during chemotherapy. They pinpointed three genes, in which mutations were clearly associated with developing neuropathy. Their next step will be to expand their study of the entire genome in as many as 1000 patients. The ultimate goal would be to use these types of genetic clues to potentially predict which patients might suffer side effects from specific drugs.

Fight Colorectal Cancer’s Board Chair Nancy Roach noted that these first findings are a long way from proving cause-and-effect, creating a test, and actually being able to get a reliable test to doctors and patients.

Source: “Gene Variations Predict Chemotherapy Side Effects,”April 9 2013 Science News.

Disclosure: Fight Colorectal Cancer has accepted funding from Sanofi, manufacturer of Eloxatin, in support of its programs. Fight Colorectal Cancer has ultimate authority over website content.

There was frost on the grass this morning when I let the little dog out.  A hard freeze is predicted for the next few nights, a sign that winter and its ice and snow isn’t far off.

Cold is a special problem for people who are getting Eloxatin® (oxaliplatin) for colon and rectal cancer.  Almost all patients on FOLFOX will experience acute neuropathy within a few hours of each oxaliplatin infusion.  This is acute, short-term, and ends within few days.

About a third will go on to a chronic peripheral neuropathy that begins as oxaliplatin doses accumulate.  Most patients will experience some tingling and numbness in their hands and feet.  A very few will have pain and difficulty walking.

Chronic neuropathy usually fades in the months after treatment ends, but may linger as long as a year or 18 months.  It remains a long-term problem for a small percentage of patients.

As cold weather approaches, you need to take care if you are on FOLFOX treatment or have peripheral neuropathy left over from previous treatment. Read the rest of this entry »

If you are diagnosed with stage III colon cancer, you will probably receive about six months of treatment with FOLFOX after surgery. Research shows that this treatment regimen helps prevent recurrence for some – but not all – patients with stage III colon cancer.  A clinical trial has been launched to answer two questions about this current standard of care:

1. Will recurrence rates go down if both FOLFOX and celecoxib (a non-steroidal anti-inflammatory drug similar to aspirin) are used for treatment?

2.  Will recurrence rates stay the same and long term side effects decrease if FOLFOX is used for three months?

Read the rest of this entry »

Colorectal cancer patients getting oxaliplatin quickly learn to avoid cold. Drinks with ice, chilly air, even opening the freezer can produce sudden, sharp pain, burning, or an unpleasant pins and needle feeling in their throat and hands.

A small study has found that venlafaxine (Effexor) can completely eliminate acute neurotoxicity from oxaliplatin in about 1 out of 3 people.  More than half of patients who took it had more than 50 percent relief from symptoms. Read the rest of this entry »