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.

Even as scientists plumb deep into cells and molecules to understand cancer, there are many immediate and “real-life” questions that researchers and clinicians are discussing at the 2013 annual ASCO meeting (American Society of Clinical Oncology).

One of the biggest puzzles for colorectal cancer is how to best treat the elderly, especially those with stages II or III (non-metastatic) cancer. It’s a huge question: today, 40 percent of colorectal cancer patients are elderly, and by the year 2030, more than 70 percent of non-inherited colorectal cancer will be among those 65 or older.

Currently, 70 years old is the median age at diagnosis, with fully 40 percent of diagnoses made in people over age 75. Yet when oncologists must consider, and explain, the risks versus benefits for treating colorectal cancer—especial stages II or III—in the elderly, there’s not enough research evidence to back informed decisions in that age group.

Lack of evidence, but elderly get chemo less often

Colorectal cancer clinical trials only enroll a minority of over-65s—and with the way current trials are designed, those probably  are the healthiest of seniors, wrote Dr. Richard Goldberg, a member of Fight Colorectal Cancer’s Medical Advisory Board, and his colleague Dr. Christina Wu also from Ohio State University, in a careful review of existing evidence. Their article, “Managing Choices for Older Patient with Colon Cancer,” one of just 133 articles among the hundreds selected for the 2013 ASCO Educational Book.

We do know that elderly patients get chemotherapy significantly less often than younger patients, according population-wide studies of patients in community practices, the authors wrote. One study found that only 58% of older-65s received chemo, compared to 84% of patients under 65.

But “it’s a disservice to classify patients based on their ..age alone,” Drs. Wu and Goldberg wrote. Doctors and patients must consider physiologic differences that can affect tolerance for chemo (e.g. body fat vs. muscle body composition; heart, liver and kidney function). Common medications (e.g. blood-thinners) can interact with chemo. Seniors who have neuropathy (i.e., numbness in feet) from diabetes or spinal stenosis perhaps shouldn’t try Eloxitin® (oxaliplatin) in the FOLFOX chemo regimen.

Life quality–and length

For elderly patients, other facts affecting treatment choices include social support—such as whether a person lives alone, and can drive or get a ride to treatments—and especially the individual’s desires for quality versus length of life.

Another paper presented at 2013 ASCO notes considerations of life-expectancy—how long the patient might expect to live—might challenge some stereotypes among both doctors and patients. In 65-year-old people (a common age for diagnosis), women have an average 18 more years of life, and men have about 14 more years. And an individual’s level of basic fitness makes a huge difference, the authors note: A healthy, fit 75-year-old man has a life expectancy of more than 14 years compared to barely 5 years for a frail 75-year-old man.

In their summary, Drs. Wu and Goldberg concluded:

“Analyses of available data in older patients…show that, as a group, they may not benefit from adjuvant chemotherapy regimens containing [Eloxitin] oxaliplatin, or at least benefit as much as younger patients. Although older patients do appear to benefit from adjuvant FOLFOX in stage III disease…the benefit is less than that observed in younger patients….It is likely that some of the fit elderly will gain value from oxaliplatin-based regimens. In advising patients, clinicians should remember that the incremental benefit from 5FU-based adjuvant therapy overshadows the incremental benefit from adding oxaliplatin to those regimens, while avoiding long-term issues with peripheral neuropathy.”

 Dr. Goldberg told Fight Colorectal Cancer, “It is particularly important for older patients to maintain very close communication with their medical team with regard to goals and priorities, as well as treatment-related side effects so that prompt and effective management of side effects can be instituted to avert modest effects from transforming into potentially serious and treatment-limiting issues. Enrollment in clinical trials is needed to help us understand management issues in older patients better. ”

Patient take-away

If you are a senior, or have a parent diagnosed with colorectal cancer, know that especially for stage II and some stage III cancers, you should take time with your oncologist to balance risks and benefits, based on your personal level of fitness irrespective of age, plus other conditions, medicines, and especially personal goals.

Sources:

• “Managing Choices for Older Patient with Colon Cancer: Adjuvant Therapy,” ASCO 2013 Educational Book ;
• ‘Approach to the Older Patient with Stage II/III Colorectal Cancer: Who Should Get Curative-Intent Therapy?” by Drs. Ramsdale, Sanoff, Muss in ASCO 2013 Educational Book
• “Future of Cancer Incidence in the U.S.,” Dec. 2008 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.

By January 1, all insurers will be required to cover routine care for patients enrolled in clinical trials. (Typically any experimental care is provided at no cost to the patient.)

“This should be seen as a step forward for the U.S. oncology community,” wrote Dr. Y-Ning Wong in the ASCO Daily News from the American Society of Clinical Oncology’s meeting in Chicago. “However, patients and providers must remain vigilant about the law’s implementation.”

Currently there is a patchwork of state laws; as of January  2014, the Affordable Care Act (ACA) creates a federally required minimum that all private insurers must cover at least the usual care when patients enroll in a clinical trial.

Medicare already must cover routine care–plus costs due to medical complications associated with participating in a clinical trial–under a rule issued by President Clinton in 2000.

The one group not covered under the new federal rule will be “grandfathered” insurance plans—those plans of large employers which haven’t changed substantially since 2010 (from 30 to 66% of all large-employer plans in 2013, it’s estimated).

Fully 70% of children with cancer enroll in clinical trials, compared to about 3% of adults, and a majority of NCI-funded adult cancer trials failing to get enough participants to continue, according to a 2010 NIH report.

“Although the new law will not resolve all the reasons adults patients with cancer do no enroll in clinical trials,” wrote Dr. Wong, “It should remove one important (and fixable) barrier.”

Source: May 31 ASCO Daily News

Long before Angelina Jolie gripped the American public’s attention by announcing her double mastectomy due to a genetic mutation, Fight Colorectal Cancer had been educating patients about family histories, plus supporting and reporting research advances in genetics—especially Lynch syndrome.

One of our most reliable sources for patient information and webinars  has been Heather Hampel, MS, CGC, a genetic counselor for 18 years, and Associate Director of the Division of Human Genetics at the Ohio State University Comprehensive Cancer Center.

We’re proud to announce that Heather Hampel is now an official member of our Medical Advisory Board. She first became aware of Fight Colorectal Cancer years ago when the late Kate Murphy, (one of our founders and Research Communications Director, who survived 30 years with Lynch syndrome) “introduced me to this group that was doing awesome work.”

Hampel is a nationally known and respected researcher in colorectal cancer genetics as first author of articles in both the New England Journal of Medicine and Cancer Research; she has served on editorial boards of many genetics journals; she is former President of the American Board of Genetic Counselors; and serves on panel overseeing national colorectal cancer screening guidelines for NCCN (National Comprehensive Cancer Network, an alliance of the world’s leading cancer centers).

Fittingly for our Medical Advisory Board, Hampel complements her academic research by keeping one foot firmly planted in direct patient care, spending one day a week counseling patients and families. As a genetic counselor, her role is to explain complex science and help families make informed, deeply personal decisions about genetic testing and medical treatments.

Lifelong path to be genetic counselor  

Heather Hampel decided at age 12 that she wanted to be a genetic counselor, when her pregnant mother had to decide about having an amniocentesis. As a high-school sophomore, Hampel challenged her favorite biology teacher: “In this teeny town of Ohio, let’s see them find someone for me to job-shadow who does genetics.” She was sent to a local university where a pediatrician allowed her to sit in on a genetic counseling session with a pregnant woman, husband, and the woman’s brother who had Hemophilia as they discussed whether the woman should be tested. “I was hooked,” Hampel said.

After getting a degree in molecular biology at Ohio State University, she ventured to New York City for Sarah Lawrence College’s graduate school—the nation’s first and still largest Master’s degree program in genetic counseling. With New York City as a melting pot for all nationalities, it’s the perfect place to study genetics in different populations—and it was home to Memorial Sloan Kettering Cancer Institute, one of fewer than five medical centers in the U.S. doing cancer genetics counseling in the mid-1990s. “It was an incredibly exciting time: six months before I started, they’d found the first breast cancer gene (BRAC1), and six months later, they found the second.” Hampel’s early research work was with the Ashkenazi Jewish population which had a specific inherited mutation for colon cancer.

Balancing research with patient care

From graduate school, she went directly to Memorial Sloan Kettering where she started a work-pattern that continues to this day of combined academic research and clinical practice. When she wanted to move back to Ohio to be nearer family, it happened to be the very moment that Ohio State University recruited the  world-famous genetic researcher Albert de la Chapelle (known for his Finnish work in colon cancer genetics) to start its Human Cancer Genetics Program.

Fifteen years later, Hampel will be helping to start a training program for genetic counselors at OSU. In her 18 years of genetic counseling, Hampel has seen genetic medicine change from a day when there were no tests for Lynch syndrome or tumor genetic analyses, to today’s explosion of discoveries, even ads for people to buy their own self-test kits. The need for reliable, up-to-date, useful genetic information has never been greater.

We at Fight Colorectal Cancer are privileged to have Hampel as a member of our Medical Advisory Board.

For more information about genetics, family history, Lynch Syndrome:

• Nov. 2012 webinar  “Talking Turkey about Lynch syndrome” and family histories, featuring Heather Hampel
• “All in the Family,” Summer 2012 newsletter article  with Hampel
• The National Society of Genetic Counselors
• “Does Colorectal Cancer Run in Your Family?” webinar with Dr. Henry Lynch and the late Kate Murphy.
• April 16 2013 Research News blog on the current Supreme Court case on patenting genes, “You don’t own me—but do you own part of my genes?”

Colorectal cancer patients and survivors who sit less and exercise more actually live longer, according to a carefully designed study published in a recent Journal of Clinical Oncology .

Researchers found that cancer survivors who got exercise equaling about 150 minutes per week of moderate to vigorous walking had a 28% lower risk of death from any cause than those who did less than 60 minutes per week of walking.

And no matter their job, people who spent 6 or more hours a day of their leisure time sitting (reading, watching TV, computer-anything) had 36% higher risk of death from any cause, than people who sat 3 hours or less per day during leisure time.

Perhaps most striking, those who reported leisure-time sitting of more than 6 hours after they were diagnosed with colorectal cancer had a 62% higher risk of dying from colorectal cancer.

This was the first-ever study of the association between leisure-time sitting and death rates, but also one of the first-ever prospective, long-term studies of exercise and survival “that was beautifully designed and analyzed” according to University of Oxford professor Dr. David Kerr.

Using a national study of 184,000 people who filled out questionnaires at the beginning of a 16-year study, researchers focused on 2293 people who developed either localized or regional—but not metastatic—colon or rectal cancer during that time. (The average time of survival after their diagnosis was almost 7 years.) They compared the participants’ reported exercise and sitting times both before and after diagnosis with death from colorectal cancer or any other cause.

The study authors wrote, “Our results add to mounting evidence that physicians should consider counseling colorectal cancer survivors to adopt a physically active lifestyle …150 minutes per week of moderate intensity activity, such as walking, and to avoid prolonged sitting.”

So shut down your computer, and go out for a walk!

SOURCES: “Associations of Recreational Physical Activity and Leisure Time Spent Sitting With Colorectal Cancer Survival,” March 1 2013 Journal of Clinical Oncology (JCO 31:876-885); Medline abstract ;“Get Off Your Bottom,” David Kerr, April 19 2013 Medscape .