September, 2006

Chemotherapy added to pre-operative radiation treatment reduces local recurrences in rectal cancer

While adding chemotherapy to radiation treatment given before surgery for rectal cancer did not improve overall survival, it did significantly reduce cancer returning locally at the surgical site.

In a clinical trial reported in the September 14, 2006 New England Journal of Medicine researchers randomly assigned rectal cancer patients who were receiving preoperative radiotherapy to:

preoperative radiotherapy without any chemotherapy
preoperative radiotherapy with chemotherapy before surgery
preoperative radiotherapy with chemotherapy after surgery
preoperative radiotherapy with chemotherapy both before and after surgery

Radiotherapy was delivered over 5 weeks before surgery. Chemotherapy consisted of cycles of 5FU (fluorouracil) and leucovorin given for 5 days per cycle. Preoperative chemotherapy was given for two cycles; postoperative chemo treatment was four cycles.

Over 1000 patients with T3 or T4 surgically resectable rectal cancers were entered in the trial. There was no significant difference in overall survival among the four groups — chemotherapy, whether given before or after surgery or not given at all had no impact on survival at five years. The combined five-year survival rate was 62.5%.

However, there was a significant difference in cancer returning to the original site in the rectum where it had been removed — local recurrence. Local recurrence rates for preoperative chemotherapy, postoperative chemotherapy, or both pre-and-postoperative chemo were 8.7%, 9.6%, and 7.6% respectively. For patients who received no chemotherapy in addition to their radiation treatment, local recurrence incidence was 17.1%.

Jean-Francois Bosset M.D. and his colleagues concluded:

In patients with rectal cancer who receive preoperativeradiotherapy, adding fluorouracil-based chemotherapy preoperativelyor postoperatively has no significant effect on survival. Chemotherapy,regardless of whether it is administered before or after surgery,confers a significant benefit with respect to local control.

Bosset et. al. New England Journal of Medicine, September 14, 2006, Volume 355:1114-1123

More information about the study is available from Medpage Today.

Posted by Kate Murphy on September 13th, 2006
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Understanding NCI — Fall Teleconferences

The National Cancer Institute sponsors regular teleconferences for cancer advocates, survivors, and their families and friends. Callers can ask questions of NCI officials during live calls. All calls are toll-free and replays are available for one month after the original teleconference.

The first teleconference is scheduled for Tuesday, September 19th and will feature newly appointed NCI Director Dr. John Niederhuber.

Update for the Advocacy Community from the NCI Director
NCI Director John Niederhuber, MD and Doug Ulman, Chair of the Director’s Consumer Liaison Group (DCLG)
Tuesday, September 19, 2006
1:00 pm (Eastern)
1-800-857-6584 Passcode: NCI
Telephone Playback available until October 19th at 1-866-372-3809

Other teleconferences in the fall schedule include:

October 31, 2006: The Impact of Nanotechnology Research on Cancer Patients
November 7, 2006: What Cancer Patients Should Know About Complementary and Alternative Medicine
December 5, 2006: Cancer Chemoprevention: A Discussion of Benefits and Risks

Details and passcodes for future conferences are available on the NCI website.

Posted by Kate Murphy on September 6th, 2006
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John Marshall MD: An overview of ASCO 2006 colorectal cancer research

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.

Posted by Kate Murphy on September 6th, 2006
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Analysis shows FOLFOX chemotherapy effective and safe for colon cancer patients over 70

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 selectedelderly patients with colorectal cancer. Its judicious use shouldbe considered without regard to patient age, although scantdata 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

Posted by Kate Murphy on September 4th, 2006
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Testing embryos for mutated colon cancer genes

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.

Posted by Kate Murphy on September 3rd, 2006
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