You can watch a recording of the webinar on our website, along with all of our past patient webinars.

Webinar: What to Do When Your Doc is Out of 5-FU from Fight Colorectal Cancer on Vimeo.

Dr. Edith Mitchell

Last night, Dr. Edith Mitchell of Thomas Jefferson University Kimmel Cancer Center in Philadelphia, PA, updated colorectal cancer patients on the latest research and treatment news in an online webinar.

Dr. Mitchell highlighted the most important news for colon and rectal cancer patients to come from the 2011 Gastrointestinal Cancers Symposium held in San Francisco last month. She answer such questions as…

“Can doctors determine the chances that my cancer may return?”

“Can my doctors determine if I need chemotherapy?”

“Does Avastin or Erbitux benefit my stage III cancer treatment?”

“Are there any promising new treatments on the horizon?”

You can view the webinar online here.

The patient webinars are a program of the Colorectal Cancer Coalition and are offered to patients at no cost. If you would like to support this program through a financial donation, visit our Donate page.

Brain MRI’s before and chemotherapy found changes in brains of women being treated for breast cancer.

Women who had breast cancer surgery but didn’t have chemo had similar changes, but they were less severe. Brains of healthy women remained stable.

Changes were in gray matter in areas of the brain involving memory and the ability to process information.

A year later most– but not all — areas of the brain had returned to normal.

The study involved 17 women who had surgery and chemotherapy, 12 women who had surgery but no chemo, and 18 healthy volunteers.

• After surgery, but before any treatment with chemo, radiation, or anti-estrogen drugs, the MRI’s of all three groups were essentially the same.
• One month after chemotherapy ended, there were MRI decreases in gray matter density in both groups of women with cancer, although changes were greater in the chemotherapy group.
• A year later, some brain density had returned in the chemo group, but changes still remained.

Changes didn’t appear to be related to any other factors than chemotherapy.  There was no correlation to surgery, severity of cancer, other treatments, or psychiatric symptoms.

Dr. Brenna C. McDonald and her team wrote,

This study is the first to use a prospective, longitudinal approach to document decreased brain gray matter density shortly after breast cancer chemotherapy and its course of recovery over time. These gray matter alterations appear primarily related to the effects of chemotherapy, rather than solely reflecting host factors, the cancer disease process, or effects of other cancer treatments.

Writing in the NCI Cancer Bulletin, Dr. Julia Rowland, Director of the NCI Office of Cancer Survivorship, says that research like this helps to understand cognitive problems cancer patients have during treatment and recovery.  She says,

The very real challenges caused by cancer-related difficulties with memory and thinking have been poorly understood and are often dismissed when reported by survivors. Findings from these studies should empower survivors to ask their medical providers what can be done to help them improve their cognitive health, especially after treatment ends.

The NCI Bulletin has more information about research into possible mechanisms forchemobrain.

SOURCE:  McDonald et al., Breast Cancer Research and Treatment, online first August 6,2010.

MRI Brain image courtesy of Arthur Toga, University of California, Los Angeles.

Many patients have to stop oxaliplatin chemotherapy with before getting its maximum effectiveness because of peripheral neuropathy — tingling, numbness, or pain in their hands and feet.  Xeloda® (capecitabine) can cause painful skin redness and cracking on the hands and feet or hand-foot syndrome, which can also affect time on chemotherapy.

Giving only six treatments of Avastin® (bevacizumab) plus XELOX chemotherapy and then stopping XELOX and using only Avastin until cancer progressed was as effective for the initial or first-line treatment of colorectal cancer as continuing XELOX.  XELOX combines Xeloda® (capecitabine) with oxaliplatin.

In addition, the strategy reduced both severe peripheral neuropathy and hand-foot syndrome.

In the MACRO study, 480 patients who had not received previous chemotherapy for metastatic colorectal cancer were randomly assigned to get either get

• XELOX and Avastin until their cancer progressed or side effects made it impossible for them to continue treatment or
• Six treatments (18 weeks) of XELOX and Avastin followed by Avastin alone until progression.

After a median follow-up of 16 months, there were no significant differences in response rate, progression-free survival, or overall survival time.

• Median progression-free survival was 11.0 months when XELOX continued and 10.3 months when XELOX was dropped and Avastin continued as a single agent.
• Median overall survival was 25.3 months with continuous XELOX and 20.7 months continuing Avastin alone.
• Overall response rate was 60 percent for the continuing strategy and 57 percent for Avastin as a single agent after XELOX was stopped.

Severe grade three or worse side effects were

• Diarrhea:  11 percent in continuing strategy and 13 percent when Avastin was used alone.
• Hand-foot syndrome:  12 percent versus 6 percent.
• Neuropathy: 24 percent versus 7 percent

The researchers also pointed out that about 1 in 10 patients in both arms of the trial were able to have successful surgery to remove metastatic tumors.

Josef Tabernero, MD, and his colleagues concluded,

Bevacizumab (BEV) as a maintenance therapy following induction XELOX-BEV was not inferior to continuation XELOX-BEV. This study suggests that maintenance therapy with single agent bevacizumab is an appropriate option following induction XELOX-BEV in patients with metastatic colorectal cancer. Further studies evaluating single agent bevacizumab after standard chemotherapy in metastatic colorectal cancer are warranted.

SOURCE: Tabernero et al., 2010 ASCO Annual Meeting Abstracts, Abstract #3501

C3 has accepted donations from Roche and Genentech in  the form of unrestricted educational grants. C3 has ultimate authority over web site content.

Combining results of four randomized clinical trials of Avastin and chemotherapy in patients with advanced colorectal cancer, researchers found that adding Avastin increased both the time older patients lived and the time before their cancer got worse.

Patients who were 70 and older had similar improvements.

There were more serious problems caused by blood clots (thromboembolic events) in patients who got Avastin, mostly related to arterial events.  However, other serious side effects were no more common in older patients than in those who were younger than 65.

Although two-thirds of patients with advanced colorectal cancer are 65 or older and four out of ten are older than 74, older patients are not well represented in clinical trials.  Even when there are no age limits on trials, they may not be enrolled because of other medical problems or a conservative approach to treatment of the elderly.

Therefore, to get a clearer idea of how adding Avastin to chemotherapy affects patients 65 and older, the research team combined information from three first-line and one second-line trial of Avastin and chemotherapy together including 1,100 patients who were 65 or older.

They found that both progression-free survival and overall survival improved when Avastin was added to chemo, and that age made little difference in benefits.

Progression-free survival time with and without Avastin was:

• For those under 65:  6.7 months vs 9.5 months
• Those 65 and older:  6.9 months vs 9.3 months
• Those 70 and older:  6.4 months vs 9.2 months

Overall survival time with and without Avastin was:

• For under 65: 16.5 months vs 19.9 months
• 65 and older:  15.0 months vs 17.9 months
• 70 and older:  14.1 months vs 17.4 months

As patients got older arterial thromoembolytic events (ATE) such as heart attack, stroke, TIA’s, and angina increased with the addition of Avastin.

• Under 65:  no difference in ATEs was found — 2 percent in both Avastin and non-Avastin groups
• 65 and older: 5.7 percent ATE for Avastin compared to 2.5 in non-Avastin group
• 70 and older: 6.7 percent ATE for Avastin, 3.2 with no Avastin

Age made no difference in other serious side effects including bleeding, hypertension, and gastrointestinal perforations.

The study authors point out that patients in clinical trials are carefully chosen and may not reflect the health of a patients in the general population.  They warn that overall health should be carefully assessed before beginning treatment.

James Cassidy and his colleagues wrote,

In conclusion, this pooled analysis of data from phase II and III metastatic colorectal cancer studies demonstrates that bevacizumab in combination with chemotherapy had a similar impact on PFS and OS in protocol-eligible older versus younger patients. Careful patient selection, however, remains important and should include an objective assessment of the patient’s physical and mental status.

SOURCE: Cassidy et al., Journal of Cancer Research and Clinical Oncology, Online First November 10, 2009.
Disclosure: C3 has accepted funding for projects and educational programs from Genentech in the form of unrestricted educational grants. C3 has ultimate authority over website content.

Compared to patients with consistently rising carcinoembryonic antigen (CEA), patients who had a CEA flare had more tumor shrinkage, longer time before their cancer got worse, and longer survival time.

Researchers measured CEA before chemotherapy started and at least twice during chemo in patients with advanced colorectal cancer who were receiving their first course of chemotherapy.

They grouped patients according to how the CEA measurements changed over time:

• flare
  
• decreasing CEA
• normal baseline CEA
• stable CEA
• increasing CEA

Comparing patients with increasing CEA measurements to patients whose CEA rose and then fell (flared):

• Overall response rate was 11 percent in increasing CEAs compared to 73 percent in flares.
• Progression-free survival time was 3.1 months compared to 8.3 months with flares.
• Overall survival was 10.9 months compared to 17.7 months when CEA flared.

A. S. Strimpakos and colleagues at the Royal Marsden Hospital in London concluded,

Compared with patients with rising CEA, flare was an independent favourable predictive and prognostic factor for tumour response and survival.

More information on the CEA flare during first-line chemotherapy  is available from Dr. Strimpakos’ poster presented at the 2009 GI Symposium.

SOURCE: Strimpakos et al., Annals of Oncology, Advance Access, October 27, 2009.

Finding the best imaging methods to diagnosis and monitor cancer and comparing new colorectal cancer screening technologies to current standards are among recommended priorities for comparative effectiveness research (CER).  The FDA reports new egg safety rules and the recall of a powdered dietary supplement.

Videos of cancer patients are now online discussing the emotional impact of their diagnosis in The Day I Found Out.

Research Reports

• Reduced uptake on FDG/PET after the first chemotherapy treatment may be able to predict how well patients will respond to chemo. In early information from a study of  advanced colorectal cancer patients reported at ASCO 2009, PET scans before initial chemo and  again two weeks later accurately predicted tumor response on later CT scans.   Dr.  Alain Hendlisz said, “Our results show that if tumor metabolism does not respond after 14 days, the patient is not likely to experience tumor shrinkage two or three months later on. Finding this out early on in treatment can help us avoid unnecessary side effects and also allows us to try another type of therapy sooner, if possible, to optimize results for our patients.”
• Chemotherapy before surgery to remove colorectal cancer that has spread to the liver makes CT scan evaluation less accurate. Doctors in France compared whether liver metastases were correctly identified in 92 patients, 30 of whom did not have chemotherapy before surgery.  CT either failed to find lesions or identified tumors that weren’t there in half of the chemotherapy patients but only about a third of those who went directly to surgery.  Other factors making CT scans less accurate were more than three liver tumors and fatty deposits (steatosis) in more than 30 percent of liver tissue.  Benjamin Angliviel and the team from the Hôpital Ambroise Paré in Boulogne report their results in the May, 2009 issue of the Annals of Surgical Oncology.

Other Headlines

• Finding the best imaging strategies for the diagnosis, staging, and monitoring of cancer is among the 25 most important priorities for comparative-effectiveness research (CER) recommended by a new Institute of Medicine report.  Comparing the effectiveness of new colorectal cancer screening methods, including CT colonographyand FIT, to usual care with FOBT and colonoscopy to prevent colorectal cancer is among the second tier of 25.  The IOM report chose 100 priorities from an initial list of 1,300 as important for $1.1 billion in CER funding to help Americans make good health care decisions based on evidence from research.  Said Dr. Harold C. Sox, co-chair of the IOM panel, “Healthcare decisions too often are a matter of guesswork because we lack good evidence to inform them.”
• Cancer survivors share their stories of diagnosis and treatment on video talking about The Day I Found Out. Developed by the Seattle Cancer Care Alliance, the videos include several colon cancer patients including C3 advocate and stage IV survivor Anita Mitchell who talks about her oncologist who gave her hope when he said, “I have a plan for you.”  She says, “All I needed was that hope.”
• The FDA has issued new rules to help reduce Salmonella infections from eggs.   Large egg farmers will have to buy chicks from bacteria safe sources, keep facilities clean and bacteria-free, test their facilities regularly, and refrigerate eggs promptly for storage and shipment.  Salmonella enteritidis causes more than 140,000 illnesses every year, some of which are life-threatening.  FDA tells consumers to buy only refrigerated eggs, check for clean and uncracked shells, refrigerate eggs promptly at home, and cook eggs until yolks are firm.
• FDA: Vital Pharmaceuticals has recalled lots of its powdered dietary supplement Stealth Chocolate and Stealth Vanilla because it may be contaminated with Salmonella. Milk protein concentrate, one of the supplement’s ingredients, was recalled by the supplier.  The dietary supplements were sold nationwide, including at GNC stores.  Consumers with questions may contact Vital Pharmaceutical Inc. at 1-800-954-7904 or 954-641-0570 during the hours of 9 am – 5 pm, Monday through Friday.

Doctors in New York followed 111 patients who had chemotherapy before surgery to remove liver metastases (neoadjuvant chemotherapy). After five years of follow-up, median overall survival was 62 months.  Overall survival was similar in three different groups:  those who had a complete or partial response to neoadjuvant chemotherapy, those whose tumors remained stable, and those whose cancer progressed during chemotherapy.

All patients the study had liver tumors that surgeons believed could be cured surgically.

Median overall survival after liver surgery:

• For all patients:  62 months
• Patients with complete or partial response to chemo: 58 months
• Patients with stable disease after chemo: 65 months
• Patients with progressive disease: 61 months

Factors that predicted better survival after surgery were:

• CEA (carcinoembryonic antigen level) less than 5 ng/dL.
• Metastatic lesions 5 centimeters or less.
• Negative lymph nodes in the primary tumor in colon or rectum.
• No cancer cells in margins of surgically removed tissue.

There was a trend for patients whose cancer progressed during pre-surgical chemotherapy to do better if they had chemotherapy infused directly into their livers after surgery (hepatic arterial infusion). Those who had HAI had 70 percent survival three years after surgery compared to 50 percent of those who didn’t.

David J. Gallagher and the team from Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University concluded,

Response to neoadjuvant chemotherapy did not correlate with overall survival even after controlling for margins, stage of primary tumor, and postoperative carcinoembryonic antigen level. Postoperative salvage treatment may have helped the survival of some patients.

SOURCE: Gallagher et al..Annals of Surgical Oncology, Volume 16, Number 7, July 2009.

Patients who got ginger (Zingiber Officinale) in capsules twice a day for three days before chemo and three days after reported significantly less nausea that those who were treated with placebo.  All patients in the study also received standard anti-nausea therapy on the day of chemo.

Almost 650 patients, mostly women, were randomly assigned to ginger supplements or a placebo in a blinded trial that will be reported at the 2009 ASCO annual meeting.

Julie Ryan, PhD, MPH, who headed the study at the University of Rochester, told reporters at an ASCO press briefing,

As many as 70 percent of patients who undergo chemotherapy experience nausea and vomiting. We found that patients who received traditional anti-nausea drugs along with ginger supplements prior to chemotherapy experienced significantly less nausea associated with their chemotherapy. However, as with all supplements, patients should speak with their doctors first before taking ginger.

SOURCE: Ryan et al., Ginger for Chemotherapy-related Nausea in Cancer Patients, ASCO 2009 Abstract #9511.

Patients who undergo chemotherapy know that every time they receive chemotherapy, oncologists take blood to test for blood counts and also for liver and kidney function.

There are many drugs which need their doses reduced or treatment held held if the kidney function changes. One of the common mistakes is that Xeloda, the oral 5-FU drug used for colon cancer, does need to have its dose reduced for kidney dysfunctions. However 5-FU and oxaliplatin don’t have to be dose reduced, which is astonishing since cisplatin has tremendous kidney toxicities which oxaliplatin does not.

Avastin needs to closely monitored for kidney toxicities. Rarely patients can develop proteinuria, which means the kidney loses too much protein. In this situation Avastin needs to be stopped. This is usually reversible within weeks. Proteinuria has been well described, particularly in patients with renal cancer. We have seen proteinuria in patients with colorectal cancer treated with Avastin, which is the reason we check a urinanalysis every 4 weeks to make sure there is no significant protein in the urine.

Patients can monitor proteinuria at home. Whenever there is a lot of protein in the urine, urine foams and makes a lot of bubbles in the toilet. Let your doctor know if this is happening.

Erbitux has also some toxicity to the kidney. It is very rare but needs to be monitored too. It can make the kidney loose magnesium. Your oncologist should test magnesium levels in the blood at every visit. Clinically patients can experience cramping in their legs and hands or can feel lethargic. Make sure magnesium levels are within normal range. This is particular important for patients who have diarrhea who may lose additional magnesium in the stool. If any of these symptoms occur you need to contact your oncologist to work you up.

In my own practice we have a number of patients who are on dialysis and treated effectively with chemotherapy. This is possible depending on the amount of the drugs being eliminated by the dialysis. Usually we treat these patients after their dialysis to allow optimal exposure of drugs to the tumor. Please discuss this with your oncologist if you have a chronic renal failure.

One of the problems for patients who have some increased creatinine levels is using contrast agents when they undergo CT scans. With any decreased kidney function you need to be very careful using IV contrast which can be harmful to your kidney. Discuss this with your oncologist.

Again for patients with kidney dysfunction, we offer very specific clinical trials which should consider if you do not qualify for other clinical trials.