An expert panel of the American Society for has issued a 2006 update of the use of tumor markers in the prevention, screening, treatment, and surveillance of gastrointestinal cancers including colon, rectal, and pancreatic cancer.

The guidelines were last updated in 2000.  This new update reviewed medical literature for evidence that specific tumor markers provided information that could help decision-making for screening and diagnosis of colorectal cancer, prognosis, progression, and recurrence. The panel also considered the role of tumor markers in predicting response to chemotherapy and other treatment.  For the first time, a recommendation for the use of a tumor marker in pancreatic cancer was included.

CEA (CARCINOEMBRYONIC ANTIGEN) AS A MARKER FOR COLORECTAL CANCER

• CEA is not recommended as a screening tool for colorectal cancer.
• CEA may be used preoperatively if it will assist in staging and treatment planning.
• CEA level is not recommended for making decisions about adjuvant treatment.
• Postoperative CEA should be monitored every 3 months for 3 years in patients with stage II or III colorectal cancer.  The panel concluded,
  • “An elevated CEA, if confirmed by retesting, warrants further evaluation for metastatic disease, but by itself does not justify systemic therapy for presumed metastatic disease.”
• In monitoring response to therapy for metastatic cancer, CEA should be measured every 1 to 8 months during active treatment.

In discussing the use of CEA to monitor potential metastatic cancer progression during treatment, the panel wrote:

Persistently rising values above baseline should prompt restaging but suggest progressive disease even in the absence of corroborating radiographs. Caution should be used when interpreting a rising CEA level during the first 4-6 wk of a new therapy, since spurious early rises may occur especially after oxaliplatin.

OTHER POTENTIAL MARKERS FOR COLORECTAL CANCER

After studying available evidence the panel concluded that there is insufficient evidence at this time to recommend the use of the following markers for screening, diagnosis, staging, prognosis, or monitoring treatment of colorectal cancer.

• CA 19-9
• DNA ploidy or flow cytometric proliferation analysis
• p53 expression or mutation
• ras oncogene
• TS (thymidine synthase), DPD (dihydropyrimidine dehydrogenase), or TP (thymidine phosphorylase)
• Microsatellite instability in the hMSH2 or hMLH1 genes
• Assaying for loss of heterozygosity at 18q or DCC (deleted in colon cancer )protein

USE OF CA 19-9 FOR PANCREATIC CANCER

• CA 19-9 is not recommended as a screening test for pancreatic cancer or as a test to determine whether surgery is warranted or what its outcomes might be.
• CA 19-9 is not recommended alone as to provide evidence of pancreatic cancer recurrence without additional imaging studies.
• Present evidence is not sufficient to recommend routine use of CA 19-9 to monitor response to treatment.  However, measuring CA 19-9 at the start of treatment for locally advanced metastatic disease and every 1-3 months during active treatment may provide an indication of progressive disease that should be verified with other studies.

Writing October 23, 2006 in an early online article of the Journal of Clinical Oncology the panel emphasized,

It important to emphasize that guidelines and technology assessments cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to
particular patients or special clinical situations, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same result. Accordingly,
ASCO considers adherence to this guideline assessment to be voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient’s individual circumstances

More specific information about the studies used to determine the recommendations is available in the Journal of Clinical Oncology.

The expert panel was co-chaired by Robert C. Bast, Jr. MD from M.D. Anderson Cancer Center and Daniel F. Hayes MD from the University of Michigan Cancer Center.  Dr. Pam McAllister, a C3: Colorectal Cancer Coalition research advocate also served on the panel as a patient representative.

One of the most troublesome side effects of oxaliplatin (Eloxatin®) chemotherapy for colorectal cancer is the development of peripheral sensory neuropathy in hands and feet.  Peripheral sensory neuropathy (PSN) includes tingling, numbness, burning pain, and difficulty using the hands or feet.  In severe cases patients may have problems walking or balancing.

An international trial is enrolling patients to learn whether or not xaliproden can reduce the severity and duration of peripheral sensory neuropathy without reducing the effectiveness of chemotherapy for metastatic colorectal cancer.  EFC5505 will randomize patients to receive either Xaliproden or a placebo during first-line chemotherapy with oxaliplatin.

Patient information about the clinical trial, peripheral sensory neuropathy, and how to enroll is available online at Chemoeffects.com.

Eligible participants include patients who:

• Have metastatic (stage IV or recurrent) colorectal cancer that cannot be treated surgically.
• Have measurable tumors.
• Have not previously received chemotherapy for metastatic colorectal cancer. (Patients with recurrent colorectal cancer who received adjuvant chemo for stage II or III disease may be eligible.)
• If they have recurrent stage II or III cancer, have been cancer-free for at least 6 months since the end of adjuvant treatment or 12 months if chemotherapy included oxaliplatin.

Factors that might exclude participation:

• Existing peripheral sensory neuropathy greater than grade 1.
• Symptoms of brain metastases
• Use of other medications that might affect peripheral sensory neuropathy
• Medical history or condition that would not allow use of oxaliplatin or 5FU.

Peripheral sensory neuropathy is related to the cumulative dose of oxaliplatin.  As treatment progresses, symptoms of peripheral neurotoxicity appear and increase.  Most patients on oxaliplatin will have some level of PSN, about 20% percent will have severe symptoms.  Once chemotherapy ends, neuropathy gets better and will disappear over time in most patients, but even after a year or 18 months a small percentage will continue to have problems.

In a previous phase III trial Xaliproden showed effectiveness in reducing the severe peripheral neuropathy — grade 3 and 4 — where there is pain or loss of function in the hands or feet although it did not reduce overall neurotoxicity of all grades.  In the Xenox trial, about 12% of those on Xaliproden experienced neuropathy severe enough to interfere with their daily activities compared to about 17% of patients who took a placebo.  Overall, about 3 in 4 patients in both Xaliproden and placebo group experienced some peripheral sensory neuropathy.

Additional assistance with choosing or enrolling in clinical trials is available through the C3 Clinical Trials Matching Service.

In a study of over 600 patients, all of whom had three different imaging tests of their colons, colonoscopy was seen as least painful and the one that they would be most willing to repeat.

Patients who had a positive fecal occult blood test, blood in their stool, iron deficiency anemia, or a family history of colorectal cancer underwent three imaging examination of the colon:

• barium enema with air contrast
• computed tomographic colonography (so-called virtual colonoscopy)
• colonoscopy

The air contrast barium enema was performed first, followed in 7 to 14 days by computed tomographic colonoscopy and optical colonoscopy  Patients completed questionnaires on all three tests and also compared exams for experiences including bowel preparation, pain, embarrassment, and overall satisfaction.

They were least satisfied with barium enema, and fewer were willing to repeat it again.  Younger adults perceived it as more painful than older people.  There were no differences between men and women in how they judged the three tests, nor were there racial differences.

Hayden Bosworth, PhD, and his colleagues reported their results in the September 2006 issue of the American Journal of Medicine.  The research team concluded:

Taking into account a wide variety of patient experience measures, patients preferred colonoscopy to air contrast barium enema and computed tomographic colonography. This finding has important implications for physicians considering different colon imaging tests.

Bosworth et.al. American Journal of Medicine, Volume 119, Issue 9, September 2006, Pages 791-799

Led by its Editor-in-Chief, Daniel G. Haller, M.D., the October 1, 2006 Journal of Clinical Oncology remembered H. Samuel Wieand, cancer researcher and biostatistician who died on June 10th.

Sam’s colleagues from the National Surgical Adjuvant Breast and Bowel Project (NSABP), Mayo Clinic, North Center Cancer Treatment Group INCCTG), and the University of Pittsburgh described his many contributions to clinical cancer research.  They also remember his humility, wit, and generosity.

Dr. Daniel Sargent writes,

Perhaps Sam’s most notable characteristic was his
sense of humor—a friendly and warm humor that welcomed friendship.With Sam, there was no distinction of people by their titles or professional stature; rather, he embraced all through his sincerity,humility, and humor. He was also the prototypical mentor, pushing
each to achieve their best while allowing and accepting short-term set-backs.

The full-text of the memorial is available online.

As of October 2006, the National Surgical Adjuvant Breast and Bowel Project(NSABP)) had completely enrolled the necessary number of patients in C-08, a Phase III clinical trial that compares two treatments for stage II and III colon cancer after surgery to remove the tumor. More than 2600 patients have been randomly assigned to either FOLFOX6, the current standard surgical adjuvant treatment, or to FOLFOX6 plus bevacizumab (Avastin®).

C-08 will evaluate whether adding bevacizumab to FOLFOX increases disease-free survival at 3 years.  FOLFOX combines oxaliplatin, leucovorin, and infusional 5FU.

While C-08 is no longer an option for stage II or III patients who want to be part of a cancer clinical trial after their surgery, there are two other large randomized trials available for them.

Stage III patients, who have completed surgery within the past 8 weeks, can enter the N0147 Phase III trial.  N0147 compares treatment with FOLFOX to FOLFOX plus cetuximab (Erbitux®).

Patients with Stage II colon cancer are eligible for E5202 which will test patients for high risk factors and then randomize high-risk patients only to either FOLFOX or FOLFOX with bevacizumab (Avastin®).  More information and links to E5202 descriptions can be found on the C3 FightColorectalCancer.Org website.

The C3 Clinical Trials Matching Service can help you enroll in either of these trials or find an appropriate clinical trial that meets your needs. Call them at 1-866-278-0392.

The National Cancer Institute provides more information about cancer clinical trials.