Fight Colorectal Cancer

Dr. John Marshall narrates webcast slide presentation of key colorectal cancer research abstracts which were presented at the June 2006 ASCO meeting in Atlanta.

• Research discussed includes:
• Giving metastatic colorectal cancer patients chemo holidays  or breaks from chemotherapy. 
• Optimal regimen for giving 5FU for first line treatment of metastatic colorectal cancer — infusional, bolus, or oral. 
• Combining all three chemotherapy drugs (FOLFOXIRI vs. FOLFIRI) as first line therapy analyzed for both effectiveness and side effects.
• Erbitux (Cetuximab) combined with chemotherapy for first-line treatment of metastatic colorectal cancer.
• Managing side effects of chemotherapy — neurotoxicity.
• Benefits and toxicity for colorectal cancer treatment for elderly patients.
• Gene expression analysis of risk and benefit for chemotherapy for early stage patients.
• Identifying patients with potentially surgically resectable liver metastases.

While designed as a continuing medical education program for health professionals, Dr. Marshall’s presentation can be understood by lay people interested in colorectal cancer research as well.  Registration is required to view the PowerPoint slides and audio.

Pooling data from four studies of FOLFOX4 treatment for colon cancer, researchers found that overall there was no significant difference in severe side effects between patients younger than 70 and those 70 year of age and older.  Treatment appeared equally effective for both groups.  The research team did point out that few patients over 80 were included in their analysis.

Although the median age for diagnosing colorectal cancer is 72, people over age 70 are not well represented in clinical trials looking at the safety and effectiveness of new treatments.  In order to find out whether FOLFOX treatment might be more toxic or less effective for elderly adults, the team looked back at data from four trials with over 3,700 people, including 614 who were at least 70.  Clinical trials included treatment after surgery for early stage colon cancer, as well as chemotherapy for those with metastatic disease.

Older patients had higher rates of grade 3 (severe)

• neutropenia — lowered white cell counts that can lead to infection.  Older patients had a 49% risk of neutropenia compared to 43% in younger patients.
• thrombocytopenia — reduced platelets or cells that contribute to blood clotting.  5% of older patients compared to 3% for those under 70.

However, they did not have more serious neuropathy, diarrhea, nausea and vomiting, or infection.

Treatment effectiveness did not differ significantly by age group either with older patients having similar response rates, progression times, and recurrence rates.

Dr. Richard M. Goldberg and his colleagues concluded:

FOLFOX4 maintains its efficacy and safety ratio in selected elderly patients with colorectal cancer. Its judicious use should be considered without regard to patient age, although scant data are available among patients older than 80 years.

Goldberg et al,  Journal of Clinical Oncology Vol 24, No 25 (September 1), 2006: pp. 4085-4091

In order to prevent passing on genes that would predispose their children to an inherited cancer, some parents are using elective in vitro fertilization (IVF) and testing cells from very early embryos for the genes that cause those cancers.  Preimplantation genetic diagnosis or PDG can help them choose an embryo free from the genetic defect for implantation into the mother’s uterus.  Couples are using PDG to select embryos that will not inherit an increased risk for colorectal cancer.

During the PGD procedure, a single cell is removed from a three-day old embryo and its genes analyzed.  It has been used since 1990 to prevent serious inherited childhood diseases, some of which are uniformly fatal.  Amniocentesis during pregnancy can also identify mutated genes, but can lead to difficult choices about aborting a growing fetus.

A small percentage (three to four percent) of colorectal cancers are directly inherited through a mutated gene.  Individuals who carry a gene for Lynch syndrome, or hereditary non-polyposis colon cancer, have an 80% lifetime risk of developing colorectal cancer.  In addition, people with the gene have an increased risk for other related cancers.  Women with Lynch syndrome have a greatly increased chance of having endometrial cancer (cancer of the lining of the uterus.)

In addition, about one percent of colon cancers result from familial adenomatous polyposis (FAP) where literally hundreds of pre-cancerous polyps line the colon.  FAP mutation carriers have a 100% risk of developing colorectal cancer without some intervention.  FAP cancers tend to occur very early, sometimes in the teens.

Children of parents who have one of the genes that cause Lynch syndrome or FAP cancers have a 50% chance of inheriting the gene from their parents.

Human genetic researchers have reviewed how preimplantation genetic diagnosis is being used to reduce the risk that children born to parents with inherited cancers will carry the mutation themselves.  Kenneth Offit and his colleagues discuss their findings in an Journal of Clinical Oncology early release published online on July 13, 2006. 

Although expensive and rare, they found cases where PGD had been used to select mutation-free embryos from parents with both FAP and Lynch syndrome in addition to other inherited cancers. They wrote,

Prenatal diagnosis and/or embryo selection after genetic testing has already been performed in the context of more than a dozen familial cancer syndromes, including the common syndromes of genetic predisposition to colon and breast cancer.

However, they were also concerned about the ethical considerations involved for patients, oncologists, and fertility specialists.  In conclusion, they said,

While constituting new reproductive options for families affected by cancer, the medical indications and ethical acceptance of assisted reproductive technologies for adult-onset cancer predisposition syndromes remain to be defined. Continued discussion of the role of PGD in the reproductive setting is needed to inform the responsible use of these technologies to decrease the burden of heritable cancers.

An article in the September 3, 2006 Sunday New York Times includes the story of Chad Kingsbury, a member of a Lynch syndrome family, who used in vitro fertilization and PGD to ensure that his daughter Chloe would not face the extra colon cancer risks that he did.

Rep. Ralph Regula (R-Dist. 16, OH), the chair of the House Appropriations Labor-HHS-Education subcommittee which oversees funding decisions for agencies such as the National Cancer Institute (NCI), promisd to maintain funding for cancer research at an August 28 town hall meeting in Wooster, Ohio.

C3 has been working with both House and Senate members to ensure an appropriate increase in NCI funding. Though Chairman Regula’s comments do not guarantee increases for fiscal year 2007, they do relieve our fears that current cuts in the House and Senate bills will ultimately be adopted.

C3 advocate Rebecca Dague raised the issue at the constituent gathering (as reported August 29 by The Daily-Record of Wooster, Ohio):

Rebecca Dague, a Medina resident struggling with colon cancer, questioned whether funding would be cut to the National Cancer Institute and research under way to find cures and new methods of treatment. Regula, whose subcommittee handles such funding, assured her otherwise.

“We’re not going to cut funding to NCI – take my word for it,” he said.

Thank you Rep. Regula. We appreciate your promise, and we look forward to working with you to make it real.

Click here to read the full article.

President George W. Bush announced on August 15, 2006 that he intended to appointed John E. Niederhuber, MD to be the 13th director of the National Cancer Institute (NCI).  Dr. Niederhuber has been acting director of NCI since June.

Before becoming acting NCI director, Dr. Niederhuber was NCI’s chief operating officer and deputy director for translational and clinical research.

He has had a long career in cancer research and treatment.  Prior to coming to NCI, he was professor of surgery and oncology at the University of Wisconsin School of Medicine in Madison.  At Wisconsin, he was also director of the University of Wisconsin Comprehensive Cancer Center, one of NCI’s 61 designated cancer centers.  Earlier, he was chair of the Department of Surgery at Stanford and held professorships at Johns Hopkins in Baltimore and the University of Michigan in Ann Arbor.

He is a graduate of Bethany College in West Virginia and the Ohio State University School of Medicine.

In a speech to the American Association for Cancer Research in April, Dr. Niederhuber talked about being able to bring the sequencing of the human genome to prevention of cancer and better treatment for individual cancer patients.

We are truly entering a new age of discovery and a new age of therapy: an age in which we will be able to specifically tailor our prevention and our treatment for each individual patient. Ladies and gentlemen, this new treatment isn’t decades away. The technology exists today. It exists because of our country’s investment in cancer research and because of the work in your laboratories.

Dr. Niederhuber’s complete biography is on the NCI web site.