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.

Protection from the Cold

Acute Neuropathy

During your oxaliplatin infusion and for the next few days

• Avoid cold drinks, very cold food, or frozen treats like ice cream.  They will cause sudden pain in your mouth and throat that is intense and may provoke frightening spasms.
• Don’t suck on ice during treatment to prevent 5-FU mouth sores.  Avoid ice altogether.
• Use pot holders or gloves to remove items from the freezer or ask for help.
• Wear mittens and warm socks to treatment and ask for a blanket.
• For a few days after treatment, stay inside where it is warm.
• If you must be outside, wear mittens, warm socks, and boots.  Cover your mouth with a scarf to avoid breathing cold air,
• If you suddenly feel spasms in your throat, relax.  You are able to breathe.  Breathe slowly and deeply in through your nose and exhaling through pursed lips.  This will help you relax until the spasm eases.

Chronic peripheral neuropathy

• Keep hands and feet warm and dry with mittens and socks.
• Talk to your doctor about your symptoms and consider lowering the oxaliplatin dose or discontinuing it altogether.

Safety First

When your hands and feet are tingling or numb, you need to take special care to avoid cuts, burns, and falls.  Serious neuropathy may affect your balance, and when you can’t feel your feet you can easily fall.

• If you can, avoid using knives and sharp tools.  Ask for help in the kitchen and with chores that require tools that might slip.
• Turn down the thermostat on your hot water heater so that your won’t burn yourself washing your hands, doing dishes, or taking a shower.
• Always use hot pads or oven gloves handling hot dishes or pans.  Ask for help if they feel heavy or hard to hold.
• Always wear shoes — indoors and outside.
• Get rid of scatter rugs and obstacles that you might trip over in the house.
• Be sure that there are railings on both sides of staircases and walk slowly on stairs.  Don’t carry baskets or bundles up and down stairs.
• Consider installing bars in the bathroom or use a shower seat.
• If you have serious problems walking or keeping your balance, ask your doctor for a referral for a home visit from an occupational therapist who can help you with home safety.

Slow down, sit down, and ask for help.

Allergic Reactions

Oxaliplatin can cause an allergic reaction that is different from the reaction to cold.  Allergic reactions can occur even after several successful treatments so,

If you experience any of the following symptoms, ask for help from the oncology nurse and your doctor immediately.

• You feel like your throat is closing up.
• You have shortness of breath.
• Your face gets red and feels hot.
• You get a rash.
• Your lips or tongue swell.
• You have a sudden cough.
• You get dizzy, sweat, or have chest pain.

There is more information about coping with oxaliplatin-induced neuropathy in the Fight Colorectal Cancer patient information section.

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

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.

The Cost of Cancer Care

In an editorial in the ASCO Daily News, published every day for ASCO attendees, Jeffrey M. Peppercorn, MD, MPH, discussed the rising out-of-pocket costs of cancer care for patients and their families.  Although cancer care costs overall are growing fast, the costs that patients bear are growing even faster.  About a third of cancer patients say they have trouble paying their bills, and one out of four have exhausted their savings.

Although the ASCO Task Force on Cost of Cancer Care calls for oncologists to discuss out-of-pocket expenses with patients, few do, and a survey found that about half of oncologists are uncomfortable talking about costs in deciding on treatment.

To learn more, join us for our next patient webinar:

The Big News in Colorectal Cancer from the 2011 ASCO Annual Meeting
June 20, 2011
8 – 9 PM Eastern time
Register to join us.

 

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.

In the trial, 48 patients who were already having pain after oxaliplatin infusions were randomly assigned to get 50 mg of immediate release venlafaxine an hour before their treatment or a placebo.  They then took an extended release venlafaxine capsule or a placebo twice a day for the next ten days, stopping the medicine two days before their next oxaliplatin treatment.

They rated their symptoms on the day of treatment and four days after it using the Neuropathic Pain Symptom Inventory (NPSI), a scale that rates 12 neurosensory feelings (for instance, burning pain, pins and needles,pain made worse by cold,pain like electric shocks, pain that is worse when something touches you).  They also reported changes in function — how well they could use their hands or feet.

Results

• 31.3 percent of patients taking venlafaxine had complete relief of symptoms compared to 5.3 percent of those on placebo.
• 58.8 percent of patients had some relief, at least 50 percent, of symptoms compared to 26.3 percent of those taking a placebo.
• None on venlafaxine had grade 3 acute neuropathy with serious pain, loss of feeling, or loss of function while 33.3 percent of those on placebo did.

Venlafaxine also improved problems with pins and needles and functioning.

There were no serious side effects for those taking the medicine.  The most common side effects were mild to moderate feelings of general weakness and nausea.

While the study showed that venlafaxine may be helpful in reducing acute neurotoxicity from oxaliplatin, it was small.  Larger trials are necessary before its safety and effectiveness can be reliably demonstrated.

Effexor® (venlafaxine) is approved by the FDA to treat depression and anxiety disorders.  While it is sometimes used off-label to treat other conditions, including diabetic neuropathy, it is not approved for acute neuropathy from oxaliplatin treatment.  Like other anti-depressants that are similar to it, it carries a warning box on its label for risk of suicidal feelings.  It may interact with a number of prescription medicines as well as some herbal products, including St. John’s Wort.

SOURCE: Durand et al., Annals of Oncology, Advance Access, March 22, 2011.

Colon cancer patients over 70 actually had a greater reduction in disease-free survival than did younger ones with a new regimen of Xeloda® and oxaliplatin compared to older IV 5-FU treatments according to a new analysis reported at the GI Cancers Symposium in Orlando.

With the bolus IV 5-FU and leucovorin regimens, stage III colon cancer patients over 70 had about a 60 percent chance of being alive and free from cancer three years after surgery. With a combination of Xeloda (capecitabine) and oxaliplatin in a treatment called XELOX, their three-year disease-free survival was 66 percent.

Younger patients had about a 3 percent absolute improvement between the two treatments from 69 percent to 72 percent.

The Xeloxa clinical trial compared the oral drug Xeloda plus intravenous oxaliplatin to then standard IV 5-FU and leucovorin regimens after surgery for stage III colon cancer. The trial (NO16968) enrolled nearly 1,900 patients, including more than 400 who were age 70 and over.

After three years, there was a six percentage point increase in disease-free survival in the older patients. The spread remained true when the cut-off age was dropped to 65. Patients 65 and older had a 62 percent chance of disease-free survival at three years on the older 5-FU treatments compared to 68 percent on the XELOX regimen.

Speaking during a GI Symposium press briefing, Daniel G Haller, MD, of the University of Pennsylvania, said,

XELOX is a new standard of care for patients with early colon cancer, regardless of age. Patients receiving XELOX immediately after surgery live disease-free for longer, and there is a trend towards superior overall survival with XELOX.

SOURCE: Haller et al., Efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-FU/LV for stage III colon cancer (NO16968): No impact of age on disease-free survival (DFS), Abstract #284, 2010 GI Cancers Symposium.

Disclosure: C3 has accepted funding for projects and educational programs from Roche and sanofi-aventis in the form of unrestricted educational grants. C3 has ultimate authority over website content.

Patients with diabetes aren’t any more likely to develop neuropathy in hands and feet when treated with oxaliplatin.

Learn more about  current colorectal cancer prevention and treatment at a Memorial Sloan Kettering CancerSmart workshop on November 12.  NIH has a downloaded booklet on palliative care, and Oncology on Canvas is looking for artwork from cancer patients and their families and caregivers.

Research Reports

• Diabetic patients have no more risk of developing peripheral sensory neuropathy when they are treated with oxaliplatin than do patients without diabetes.  A pooled analysis looked at three studies totalling almost 1,600 patients.  Of those, 135 or 8.5 percent had diabetes.  The percentage of patients without diabetes and with diabetes who developed neuropathy was almost identical for each grade:  45.0%/46.7% (grade 1), 28.6%/26.7% (grade 2), and 13.0%/12.6% (grade 3).   Diabetic patients who had neuropathy before beginning treatment with oxaliplatin were not included in the study.  R. K. Ramanathan reported results from clinical trials for first and second line metastatic colorectal cancer and the adjuvant MOSAIC trial in the Annals of Oncology Advance Access, November 3, 2009.

Other Headlines

• Memorial Sloan Kettering Cancer Center offers An Update on Colorectal Cancer next Thursday, November 12, from 6:00 to 7:30 pm. Oncologist Leonard Saltz, MD,  surgeon José Guillem, MD, MPH,  and radiation oncologist Karyn Goodman, MD will discuss up-to-date information on screening and treatment for colorectal cancer.  Part of MSK’s CancerSmart, the program will be held at the MSKCC Rockefeller Research Laboratories, 430 East 67th Street in New York City.  Call 212-639-3074 for more information.
• The National Institute of Nursing Research has a booklet for patients and families that can be downloaded: Palliative Care: The Relief You Need When You’re Experiencing the Symptoms of Serious Illness. In explaining that palliative care is different from hospice care, the booklet says, “Palliative care is available to you at any time during your illness. remember that you can receive palliative care at the same time you receive treatments that are meant to cure your illness. its availability does not depend upon whether or not your condition can be cured. The goal is to make you as comfortable as possible and improve your quality of life.”
• Oncology on Canvas provides a way for people affected by cancer to express their experiences through art.  The 2010 competition is now open.  Registration must be submitted by June 10, 2010 and artwork completed by June 30, 2010.  Work in watercolor, oil, pastel, photography, acrylic or mixed media is acceptable.  Artists must be someone diagnosed with cancer, or a family member, friend, caregiver or healthcare provider of a person diagnosed with cancer.

Roche announced results of a Phase III clinical trial that compared XELOX chemotherapy to bolus 5-FU and leucovorin.  The trial, nicknamed XELOXA (NO16968), enrolled almost 1,900 patients in 29 countries.

Its primary goal was to see if combining the oral drug Xeloda® (capecitabine) with Eloxatin® (oxaliplatin) could improve disease-free survival for stage III colon cancer patients.

In a press release, Roche said that full results of the trial will be presented at upcoming scientific meetings.

Patients were randomly assigned to one of two trial arms for a total of 24 weeks after their surgery:

• XELOX:  8 treatment cycles consisting of IV oxaliplatin on day 1, oral capecitabine on days 1-14, 7 days of rest.
• 5-FU/LV:  Bolus IV injections of 5-FU modified by IV leucovorin in either the Mayo Clinic plan or Roswell Park plan depending on center.

Further analyses of the XELOXA trial are planned to determine:

• Whether XELOX improves overall survival.
• Whether patients find the XELOX treatment more convenient and are more satisfied with it.
• How much medical care is used with both treatments.

An analysis of XELOX safety and side effects was published in 2007 in the Journal of Clinical Oncology. That study found that overall treatment side effects were similar in both the XELOX and 5-FU/LV groups, but the type of side effects differed.

• Overall, patients on XELOX experienced less diarrhea and hair loss, but they had more neuropathy, vomiting, and hand-foot syndrome than those who got FU/LV.
• Compared to the Mayo Clinic 5-FU treatment, patients on XELOX had more serious (grade 3-4) GI side effects and fewer changes in blood counts.
• Compared to the Roswell Park regimen, XELOX patients had fewer serious GI problems and more changes in blood counts.
• Treatment-related deaths (6 per 1000) were the same in both groups.

William M. Burns, CEO of Roche’s Pharmaceuticals Division, said,

While Xeloda is already approved for the treatment of early-stage colon cancer as monotherapy, the results of this study mean that physicians will now be able to offer their patients Xeloda as a combination chemotherapy. This is an important development for patients as colon cancer, if caught early enough, can be cured, so physicians need a wide range of treatment options.

Roche is planning to ask health authorities to extend the current Xeloda labeling to include use with oxaliplatin for stage III colon cancer.

Disclosure: C3 has accepted funding for projects and educational programs from Roche in the form of unrestricted educational grants. C3 has ultimate authority over website content.