Adding Erbitux® to a standard colorectal cancer chemotherapy treatment that also included Avastin® did not increase mortality according to initial reports of a randomized clinical trial for patients with advanced colorectal cancer.

The trial — CAIRO2 — conducted in Europe compared CAPOX plus Avastin to CAPOX plus both Avastin and Erbitux.  CAPOX combines the oral chemotherapy drug Xeloda® (capecitabine) with intravenous Eloxatin® (oxaliplatin.) Patients in the trial had advanced (metastatic) colon or rectal cancer, and this was their first chemotherapy for advanced cancer.

755 patients took part in the trial.  The study measured how long patients lived before their cancer grew or progression-free survival.

Analyzing safety information for the first 400 patients, researchers found an expected difference in serious toxicity when Erbitux was added to the standard treatment.  However, this was entirely due to skin rash, a known and common side effect of Erbitux.  Overall grade 3 and 4 toxicity from all causes was 81 percent in the experimental arm and 72 percent in the arm without Erbitux.

There was no increase in gastrointestinal side effects treatment-related deaths.

This analysis did not include information on the effectiveness of the new combination.

Writing in the Annals of Oncology, the Dutch Colorectal Cancer Group, concluded,

The addition of cetuximab to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of advanced colorectal cancer appears to be safe and feasible. No excessive or unexpected toxicity in the cetuximab-containing treatment arm was observed.

SOURCE: Tol et al., Annals of Oncology, advanced access published online February 13, 2009.

25 mcg/hr Duragesic® patches manufactured by ALZA corporation and sold by PriCara® or Sandoz in the United States are being voluntarily recalled.  The recalled lots have expiration dates on or before December, 2009.  Duragesic patches manufactured by ALZA and sold in Canada are also being recalled.

The recall does not affect other Duragesic strengths:  12.5, 50, 75, or 100 mcg/hr. Durogesic™ patches sold in Europe, Latin America, and Asia are also not included in the recall.

The patches may have a cut along the side of the reservoir that contains fentanyl gel potentially letting the gel leak into the patch packaging.  Fentanyl is a powerful opioid drug, and exposure to the gel could lead to dangerous effects which can be fatal.

Anyone with 25 mcg/hr Duragesic patches should check the box and the individual foil packages for expiration dates.  Do not open the foil packaging if you have any question about the safety of the patch inside.  Do not handle a potentially damaged patch.

Contact your doctor if you have concerns about what to do about pain management.

In the news release announcing the recall, Johnson and Johnson, the parent company of PriCara said,

Anyone who comes in contact with fentanyl gel should thoroughly rinse exposed skin with large amounts of water only; do not use soap. Immediately dispose of affected patches with cut edges by flushing them down the toilet, using caution not to handle them directly. Patches with a cut edge that have leaked gel will not provide effective pain relief.

Johnson and Johnson also says,

Anyone with 25 mcg/hr DURAGESIC patches being recalled should call 800-547-6446.

Anyone with 25 mcg/hr Sandoz Inc. patches being recalled should call 800-901-7236.

Patients using fentanyl patches who have medical questions should contact their health-care providers.

The FDA has previously issued a public health advisory about the safe use of fentanyl patches.

WHAT THIS MEANS FOR PATIENTS

Patients and their caregivers who are using the 25 mcg/hr Duragesic patches to manage pain should immediately check the box or foil package to see if the expiration date is on or before December 2009.

If so, do not open the foil package and do not handle the patch itself directly.

If you do get some gel on your hands, rinse them immediately with large quantities of water without soap.

All fentanyl patches of any strength should always be disposed of by putting sticky sides together and flushing down the toilet.  Don’t handle the 25 mcg patches directly while disposing of them.

Call your doctor about managing pain relief.

Call either Duragesic (800-547-6446) or Sandoz (800-901-7236) for information about the next steps in returning the patches.

A small fiber-optic probe the size of a pen that analyzes light shone on colorectal tissue just inside the rectum can predict whether or not there are precancerous polyps in other places in the colon.  Using enhanced backscattering spectroscopy or EBS, light that scatters back into the probe can provide a great deal of information about the smallest details of cells, including changes in normal cells that reflect more dangerous precancerous changes elsewhere in the colon.

Its inventors believe that it will be an important screening tool for colorectal cancer, accurately predicting people who need to have a full colonoscopy to find precancerous polyps or early colon cancer.

Vadim Backman, professor of biomedical engineering at the McCormick School of Engineering at Northwestern University in Chicago, developed the technique and has been testing it with Dr. Hemant Roy, gastroenterologist and associate professor at Northwestern’s Feinberg School of Medicine. They call it four-dimensional elastic light-scattering fingerprinting (4D-ELF).

In both mice and a pilot study of human colonoscopies, analysis of backscattering in normal tissue was able to predict the risk for precancerous changes throughout the colon.

In the pilot testing on 63 people undergoing colonoscopy, 4D-ELF was able to predict 100 percent of precancerous polyps.  Although some people without polyps also were identified as potentially needing colonoscopy, the screening with 4D-ELF reduced the need for colonoscopy by two-thirds.

Writing in Clinical Cancer Research, Dr. Roy said,

Finally, in pilot human studies, we observed that LEBS analysis of the endoscopically normal mucosa was able to detect differences in patients who harbored adenomas when compared with those who were neoplasia free. Thus, the technical advance of LEBS may potentially translate into a practical means for colon cancer screening.

With funds from the National Cancer Institute, Dr. Roy is testing 4D-ELF on 1,250 people who are having colonoscopies with the goal of developing rules for who may need a full colonoscopy based on 4D-ELF screening and who does not need further testing.  He will also be looking at patients with inherited colorectal cancer syndromes (HNPCC and FAP) to see if the probe can be helpful in surveillance for them.

The technology is also being explored for pancreatic cancer where the probe is used during routine endoscopic biopsies of the duodenum to find cancer in the pancreas.  Screening high risk families may find pancreatic cancer early enough to cure it.

An article on Dr. Backman’s research appeared in the Chicago Tribune.

SOURCE: Roy et al. Clinical Cancer Research, Volume 12, February 2006.

WHAT THIS MEANS FOR PATIENTS

Enhanced backscattering spectroscopy analysis is still experimental and is not available outside of clinical research.

While it shows promise as a colorectal screening method, people who need colorectal cancer screening should not delay their own screening in anticipation of this technology.

All people of average risk should be screened for colorectal cancer by one of the currently approved methods:  fecal occult blood tests, flexible sigmoidoscopy, double-contrast barium enema, or colonoscopy.

People with higher than average risk should be screened with colonoscopy on a schedule determined with their doctors.

Children and teens who have a confirmed mutation for familial adenomatous polyposis (FAP) are being recruited for a randomized clinical trial of Celebrex® (celecoxib).  The study wants to know if Celebrex can increase the time before polyps begin to develop or reduce the number of polyps.

Familial adenomatous polyposis or FAP is an inherited condition, passed directly from parent to child.  People with FAP develop hundreds, sometimes thousands, of polyps that literally carpet their large intestine due to a mutation in the APC gene which regulates cell growth.

Without intervention, polyps eventually progress to colorectal cancer. Polyps usually begin to appear in early teens with an average age for developing cancer of 39.

In order to be eligible, children must

• Be between the ages of 10 and 17.
• Have a confirmed genetic mutation for FAP.
• Have no more than 20 polyps, which must be removed before the study medicine is given.

Young people with attenuated familial adenomatous polyposis,  a different form of FAP with fewer polyps, are not eligible for the trial.

The study is being conducted in Spain and in Tennessee and Texas in the United States.  In the double-blinded study, half of the children in the trial will receive Celebrex, half a placebo.

Request information about a study center or call Pfizer CT.gov Call Center    
1-800-718-1021.

Although there are no clear guideposts to predict how long patients with cancer and chronic illness will live, all patients approaching the end of life should be assessed regularly for pain, breathlessness, and depression.  End of life or palliative care should not wait until patients are very close to death.

New clinical guidelines for palliative care at the end of life have been developed by the American College of Physicians based on known evidence for meeting the physical, psychological, social, and practical needs of patients and their caregivers. 

End of life is defined as that time when a person is living with an illness that will worsen and eventually cause death.  Good care can prevent or reduce suffering and provide support for patients and their families during a difficult time.

Strong recommendations from the ACP for patients with serious illness at the end of life include:

• Health professionals should regularly assess patients for pain, breathlessness, and depression.
• Therapies with proven effectiveness should be used to manage pain.  For cancer patients this includes nonsteroidal anti-inflammatory drugs (NSAIDS), opioids, and biophosphonates.
• Therapies with proven effectiveness should be used to manage breathlessness (dyspnea) which includes oxygen for short-term relief and opioids when dyspnea is unrelieved.
• Therapies with proven effectiveness should be used to manage depression.  For patients with cancer this includes, tricyclic antidepressants, selective serotonin reuptate inhibitors (SSRIs), or psychosocial therapy.
• Health professionals should ensure that advance care planning happens and advance directives are in place.

Studies have found that there is better use of palliative care and better outcomes for patients when

• Multidisciplinary teams involve nurses and social workers.
• Collaboration leads to continuity of care and service coordination.
• Communication is facilitated.

In addition, health teams should routinely screen family caregivers for emotional and practical needs as they care for patients at the end of life.

Planning for an individual’s end of life care should begin as early as possible in the course of a serious illness and be reassessed when medical situations change.

Headed by Dr. Amir Qaseem, the clinical guidelines team summarized:

Symptom control, continuity in care, and reducing caregiver burdens are critical elements of care for managing patients nearing the end of life. In addition, following appropriate treatment strategies for pain, dyspnea, and depression substantially affect patients’ end-of-life experiences.

Interventions where advance care planning includes trained facilitators (including palliative care providers), involves key decision makers, and addresses care across settings are beneficial for improving care.

Further research on potentially beneficial but understudied interventions, and conditions other than cancer, should be a high priority.

SOURCE: Qaseem et al. Annals of Internal Medicine, Volume 148, Number 2, January 15, 2008.