Fight Colorectal Cancer

Doctors found no objective responses to a combination of Xeloda™ (capecitabine) and thalidomide in a small study of patients whose tumors had progressed on standard chemotherapy.  About a third of patients (38%) achieved stable disease on the regimen, but no tumors got smaller.

In a phase II clinical trial, 34 patients received oral capecitabine twice daily along with oral thalidomide.  Median progression-free survival on the regimen was 2.6 months; median overall survival was 7.1 months.

Serious side effects (grade 3 or 4) included fatigue (15% of patients), blood clots in veins (12%), sleepiness (12%), and constipation (9%).  15% of patients had grade 2 hand-foot syndrome.

In a report in the February 2006 American Journal of Clinical Oncology, the research team concluded:

Though well-tolerated, the combination of capecitabine and thalidomide was not associated with objective tumor responses in a population of patients with previously treated metastatic CRC.

After 7 years of follow-up, there was no difference in the incidence of colorectal cancer between women who received daily supplements of calcium and vitamin D and women who received a placebo according to a report in the February 16, 2006 issue of the New England Journal of Medicine..

As part of the Women’s Health Initiative, over 36,000 postmenopausal women randomly received a twice daily supplement of 500 mg of calcium plus 200 units of vitamin D3 or a placebo.  Neither the women or their doctors knew whether they were getting the supplements or the placebo.

Incidence of colorectal cancer did not differ significantly between the two groups. There were 168 cases of cancer in the supplement group and 154 among those taking placebo.  For those with cancer, tumor characteristics were similar.  Frequency of colorectal screening and abdominal symptoms were also the same.

The researchers did point out that seven years might be too soon to judge whether the supplements were effective given the long time period for the development of colorectal cancer.  They will continue to follow the women to see if there will be a difference over time.

The Women’s Health Initiative research team concluded:

Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention.

In a companion study also reported in NEJM, the same women were assessed for hip fracture risk.  Although there was a small improvement in hip bone density after 7 years of supplements, there was no difference in hip, spine, or overall fractures.  In addition, there was an increased risk of kidney stones in those taking daily calcium plus vitamin D3.  for a subset of women over 60, there was a 20% reduction in risk of breaking a hip.

Another story on the study is available on MedPage Today.

Genentech, the manufacturers of Avastin, announced on February 12, 2005 that they were temporarily suspending enrollment in a large, international trial of Avastin™ (bevacizumab) and chemotherapy for early-stage colon cancer to give safety monitors an opportunity to review information about an unusually high number of deaths of patients in one arm of the trial.

In addition, enrollment to the trial has been unexpectedly high — over 200 patients a month — and data safety monitors need more time to ensure that trial treatment is safe.

The AVANT trial compares three regimens for treating stage III and high-risk stage II colon cancer after surgery to remove the tumor in the colon.

• ARM A:  FOLFOX (oxaliplatin, leucovorin, and continuous infusion 5FU) alone
• ARM B:  FOLFOX plus Avastin™ (bevacizumab)
• ARM C:  XELOX (oxaliplatin and oral capecitabine) plus Avastin™

Since the study opened in December of 2004, there have been an usually high number of participant deaths in Arm C — the XELOX plus Avastin arm.  Excluding deaths from recurrent colon cancer, there have been

• 4 deaths (0.6%) in Arm A
• 3 deaths(0.4%) in Arm B
• 7 deaths (1%) in Arm C

Accrual to the trial has been rapid, with over two-thirds of the targeted 3,450 participants enrolled by January 2006.  The trial is being conducted internationally, including in the United States, in 308 centers in 33 countries.  Patients who have already been enrolled in the trial will continue treatment.

Gastrointestinal perforation rates in the trial have been about 1%, lower than those in previous trials with Avastin™ for people with metastatic colorectal cancer.

Roche, the manufacturers of Eloxatin™ (oxaliplatin), also released information about the trial suspension.

Another Phase III trial for stage II and III patients that compares FOLFOX alone to FOLFOX plus Avastin™ will continue accrual.  NSABP C-08 is a two-arm trial that does not include a capecitabine regimen.  The National Surgical Adjuvant Breast and Bowel Project (NSABP), a cooperative group conducting the trial, has consulted with their own Data Safety Monitoring Board.  The DSMB has found no discrepancies in either deaths or gastrointestinal perforation in the C-08 trial participants.

On February 6, 2006 the President proposed a budget freeze for the National Institutes of Health (NIH) in 2007 which will hold its funding steady at $26.6 billion. Most of NIH’s 27 institutes and centers will ge a slight cut under the President’s plan. The budget designates $4.75 billion for the National Cancer Institute which is a $40 million cut from fiscal year (FY) 2006.

The following quote if from the article “NIH Faces a Tough Budget Year” by Jocelyn Kaiser on the ScienceNOW Daily News web site:

“We’re not in a position to do as much as many of us would like,” said Michael Leavitt, secretary of the Department of Health and Human Services, at a budget briefing today. When asked why biomedicine was not included among the science agencies funded by the president’s American Competitiveness Initiative, NIH Director Elias Zerhouni explained that the physical sciences are “complementary” to NIH’s mission. “I don’t think biomedicine is necessarily less urgent … but you have to make choices that are not necessarily going to make everybody happy.”

The FY 2007 NCI funding comes on top of the hard cut it received in the FY 2006 budget. The 2006 budget gave a slight increase to NIH and NCI but when the one percent across the board cut to domestic discresionary programs enacted is factored in the increase becomes a decrease. Go here to read a previous post on the FY 2006 budget.

Congress took a bold step forward in 1998 when it promised to double the NIH budget within five years. Congress kept that promise and opend the floodgates to countless new opportunities and advances in cancer research and programs. The result is that cancer survivorship rates have steadily increased each year and for the first time since 1930 the number of cancer deaths in the United States decreased in 2003.

This research momentum will not continue without a stable and reasonable level of funding increases. Less funding translates into fewer discoveries, fewer new drugs in development, and fewer new treatments reaching patients.

In 2003 I made my first visit to Washington, D.C. to talk to my Senators and Representative as a part of the One Voice Against Cancer Lobby Day. One of the speakers quoted the President as saying, “In order to win the war against cancer we must fund the war against cancer.” I want to see deeds not just hear words.

Making cancer a national priority will save millions of lives, reduce untold suffering, and save the nation billions of dollars in healthcare costs now and in the future. The investment is surely worth it.

The transcript of the People Living with Cancer chat with Dr. Richard Schilsky is now available on the PLWC site.

Dr. Schilsky discussed Gastrointestinal Cancers: Scientific News for Patients on January 26, 2005 as part of the PLWC chat program.

He answered questions from family members and patients with colorectal, gall bladder, pancreatic, gastric, and esophageal cancers during the online chat.

In response to a question about new screening tests for colorectal cancer, he said:

Virtual colonoscopy and stool DNA testing are very exciting new approaches to screening for colorectal cancer. Virtual colonoscopy, which is a CT scan, seems to be as accurate as conventional colonoscopy in detecting colon polyps that are of a moderate or large size.

Stool DNA testing is still being evaluated, but it has the potential to be a better test than looking for blood in the stool because it is more specific for the presence of malignant cells.

Another question was asked about the limiting factors for using bevacizumab (Avastin) for treating advanced colorectal cancer.  Dr. Schilsky replied:

Generally speaking, bevacizumab is given together with chemotherapy for patients with advanced colon cancer. Most of the time, the bevacizumab treatment is stopped when the cancer progresses.

Bevacizumab can have many side effects, including high blood pressure and a risk of perforation of the bowel, and there is very little information on how long bevacizumab can be given safely.

Throughout March, Dr. Robert Mayer from the Dana-Farber Cancer Institute will answer email questions about Preventing, Screening, and Treating Colorectal Cancer.  You can down load a flyer with more information, submit a question, request a transcript, or find links to recommended reading on PLWC.