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.

The antidepressant drug Duloxetine (Cymbalta®) was shown in a recent study to provide pain relief to people suffering from peripheral neuropathy caused by chemotherapy.

Chemotherapy drugs such as oxaliplatin (Eloxatin®, used in the FOLFOX regimen for colorectal cancer) can damage “peripheral” nerve cells (those beyond the brain and spinal cord), causing pain, tingling, numbness especially in feet and/or hands. This side effect, called chemotherapy-induced peripheral neuropathy (CIPN), can worsen over time and last long after the chemotherapy has stopped. (More information on CIPN can be found here.)

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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 »

While there weren’t new blockbuster announcements for colorectal cancer this year at the American Society for Clinical Oncology’s (ASCO) Annual Meeting, there was plenty of focus on making what we already have work better and on choosing the patients who will benefit the most from treatments, as well as those who might not be helped at all. (Note, many of these issues will be discussed in detail on our upcoming patient webinar.)

Highlights:

• While adding oxaliplatin to 5-FU improves five year survival slightly for stage II colon cancer, it increases side effects, particularly tingling and numbness in the feet.  An analysis of several NSABP trials found that two or three more stage II patients out of every 100 would be alive five years later if they were given oxaliplatin in addition to 5-FU than if they only got 5-FU.  Risk of cancer returning was similar with an absolute improvement of 3 to 5 percent, depending on risk factors.  Doctors and patients need to think about whether the small benefit is worth the risk of neuropathy that may become permanent.
• Two speakers at the Saturday colorectal cancer oral abstract session addressed adding oxaliplatin to 5-FU as part of pre-surgical chemoradiation treatment for rectal cancer.  NSABP R-04 found that oxaliplatin did not help increase complete response rates, avoid colostomies, or downstage cancers. It did increase diarrhea significantly. On the other hand, early results from a German trial did find an increase in complete responses with oxaliplatin, and they didn’t see worse side effects.
• In the PRIME phase III clinical trial, patients receiving their first treatment for advanced colorectal cancer who had normal or wild-type KRAS genes in their tumor did better when Vectibix® (panitumumab) was added to FOLFOX chemotherapy.  But those patients whose tumor KRAS was mutated actually did worse than patients who only got chemotherapy.
• Side effects, while difficult for patients, may predict better outcomes from treatment.  Patients who got capecitabine as part of pre-surgical chemoradiation and developed hand-foot syndrome had fewer recurrences three years later and better survival at five years.  In another study of breast, lung, and colorectal cancer, patients who got high blood pressure while on Avastin® (bevacizumab) lived longer and it took longer before their cancer got worse.

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Infusions of calcium and magnesium can reduce numbness and tingling caused by oxaliplatin without affecting survival, according to a recent study in the Netherlands.  But the infusions didn’t affect treatment success.

Most colorectal cancer patients being treated with oxaliplatin chemotherapy experience some sensory peripheral neuropathy that may vary from mild tingling in their hands and feet to pain and difficulty walking.  Although peripheral neuropathy usually gets better within a few months after treatment ends, it can last years for some patients.

Sometimes patients need to stop oxaliplatin treatments before they get full advantage from them because of this troublesome side effect. Read the rest of this entry »