Fight Colorectal Cancer

NEWS FROM ASCO 2007

In an effort to predict which patients might benefit the most from treatment with cetuximab (Erbitux), researchers studied three biological markers in both primary and metastatic colorectal cancers. 

They measured EGFR (epidermal growth factor receptor) levels using both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests.  They also measured cchanges copy numbers of the HER2 gene with FISH.  In addition, they tested for mutations in the KRAS gene.

• While IHC tests of EGFR showed no difference in response rates, FISH EGFR positive patients had a significantly higher response rate to cetuximab — 29.3 percent had tumor shrinkage compared to 6.8% of those with negative EGFR FISH.
• Positive EGFR by FISH testing almost doubled the median time to when the cancer began progressing again — 6.6 months versus 3.7 months.
• Increased HER2 gene copy number was associated with shorter time to progression and survival.
• KRAS mutation carriers had a significantly lower response rate (6.4 percent versus 26.5 percent).  They also had shorter median time to progression  (3.7 months versus 6.3 months) and shorter survival (8.3 versus 10.8 months).

Giovanna Finocchiaro  M.D. presented the results of the study at ASCO:

This study, the largest biomarker analysis in colorectal cancer patients treated with cetuximab, shows a significant benefit in response and TTP for EGFR FISH positive patients. KRAS mutation analysis identifies a group of patients with the lowest chance to benefit from the therapy. Increased HER2 gene copy number predicts early escape from cetuximab therapy.

Combining EFGR status determined by FISH analysis and KRAS mutations may predict those patients most likely to benefit from cetuximab and help others avoid its expense and side effects.

SOURCE:  Finocchiaro et. al. Abstract #4021 ASCO 2007

NEWS FROM ASCO 2007

When cetuximab (Erbitux®) was added to a combination of irinotecan, leucovorin, and fluorouracil (FOLFIRI), both response rates and progression-free survival improved.

The phase III CRYSTAL trial randomized 1200 patients who had not had previous chemotherapy for metastatic colorectal to receive either

• Standard arm: FOLFIRI regimen of intravenous irinotecan and leucovorin followed by a 46 hour continuous infusion of 5FU every two weeks.
• Experimental arm: Weekly infusion of cetuximab added to the FOLFIRI treatment.

Cetuximab improved progression free survival by 15%, with median time to when cancer got worse of 8.0 months for FOLFIRI alone and 8.9 months for the combination treatment of FOLFIRI plus cetuximab.

At one year 23 percent of patients on FOLFIRI had not had any progression compared to 34 percent of those on the experimental cetuximab arm.

More patients had their tumors shrink while on the experimental arm that included cetuximab (46.9 percent versus 38.7 percent).

Three times as many patients on the cetuximab arm were able to have liver metastases successfully removed. (6 percent vs. 2.5%).  Among patients whose only metastases were in their livers, nearly 10 percent who initially could not have a surgery to remove them were able to have complete resection surgery after treatment with the FOLFIRI plus cetuximab.

Grade 3 or 4 serious side effects included low white cell counts, vomiting, and fatigue that were similar in both arms.  There was slightly more severe diarrhea in the cetuximab arm (10.5 percent versus 15 percent.)  Nearly 20 percent of the cetuximab patients experienced a serious skin rash, and 2.3 percent had a reaction during the infusion.

Skin reactions were strongly related to length of progression-free time, with those having the most severe rash also having the longest progression-free survival.

Eric Van Cutsem reported the CRYSTAL results at ASCO, concluding:

Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone.

WHAT THIS MEANS FOR PATIENTS

Patients newly diagnosed with metastatic colorectal cancer have another option for treatment.  The FOLFIRI plus cetuximab treatment may be especially helpful to those with with liver-only mets that are initially not able to be removed surgically — shrinking them so they can be treated with surgery and potential cure.

Surgeons at New York Presbyterian Hospital will demonstrate a new technique for surgical treatment of colon polyps that cannot be removed during normal colonoscopy during a live webcast on June 20, 2007.

• Advances in Colorectal Cancer Therapies
• June 20, 2007
• 8:00 P.M. (Eastern Daylight Time)
• Jeffrey W. Milsom, MD, Richard L. Whelan, MD, Alfred I. Neugut, MD, PhD, Joseph T. Ruggiero, MD
• New York Presbyterian Hospital, New York NY

Polyps (adenomas) found during colonoscopy need to be removed to prevent their developing into colon or rectal cancer.  They also need to be examined more carefully for existing cancer cells.

However, some polyps in difficult-to-reach places or those that are flat against the colon wall cannot be removed during colonoscopy.  Traditionally, open abdominal surgery was necessary to remove and biopsy them.

New York Presbyterian doctors have developed a laproscopic approach to locating and removing these polyps.  Abdominal laproscopy is combined with colonoscopy, and carbon dioxide is used to inflate the colon during the procedure.

The new technique avoids lengthy three to seven day hospital stays for recovery after open surgery.  Most patients will be able to go home in less than a day.

Webcast viewers will be able to email questions during the surgery.  Replays are available online after the live date.

To see the webcast go to the NY Presbyterian Live Webcast site on June 20th at 8:00.

The webcast programming is managed by OR-Live.

Getting the colon free of stool and ready for colonoscopy is a major challenge.  In some studies fully one third of people say that the prep is the key barrier to their being screened for colorectal cancer.

Gastroenterologists offer a variety of strong laxatives designed to completely cleanse the colon from a gallon of polyethylene glycol solution  (PEG) to a much smaller volume of sodium phosphate liquid (Eleet Phospho-soda®).  In recent years sodium phosphate has been available in tablet form (Visicol® and OsmoPrep®). 

The Halflytely® bowel preparation reduces the amount of PEG solution to two liters and adds four bisacodyl laxative tablets.

In order to compare the  safety and colon-cleansing effectiveness of sodium phosphate tablets to the two-liter PEG prep, researchers randomized 481 adults having a colonoscopy to use either

• 32 sodium phosphate tablets with clear liquid of their choice
• 2 liters of PEG solution plus 4 bisacodyl tablets

Colonoscopists did not know which prep their patients had received and rated cleansing from excellent to inadequate both overall and for the ascending colon.  The sodium phosophate tablets were significantly better than the PEG solution for cleaning stool in both assessments.

Patients who took sodium phosphate tablets were less likely to have gastrointestinal symptoms including bloating, abdominal pain, or vomiting than those who used PEG plus the bisacodyl: (64 percent versus 79 percent.) Overall, adverse events were less likely for the sodium phosphate tablets than for the PEG liquid (66 percent versus 82 percent.)

Both groups had changes in laboratory tests, but fluctuations were more common with sodium phosphate tablets especially for phosphorous, sodium, and potassium.

Led by John F. Johanson, M.D., the team concluded,

The colon-cleansing efficacy of the new 32-tablet NaP dosing regimen in this study was found to be significantly better than the 2L PEG solution plus bisacodyl tablets regimen. The 32-tablet NaP dosing regimen was associated with fewer adverse events. As expected electrolyte shifts were more common and of greater magnitude in the NaP group compared with the PEG plus bisacodyl group; however, both treatment groups demonstrated significant changes in electrolytes and creatinine.

SOURCE:  Johanson et. al., American Journal of Gastroenterology, early online articles, June 15, 2007.

WHAT THIS MEANS FOR PATIENTS

Patients preparing for a colonoscopy can feel comfortable that sodium phosphate tablets will clean the colon as well as or better than a two liter container of PEG solution.

They may have less bloating, cramping, and vomiting with the tablets.

However, patients with kidney or cardiac problems will want to discuss the choice of colonoscopy prep carefully with their doctors since there is a greater change in body electrolyte balance with tablets.

I ventured up to Capitol Hill this morning for one last ditch effort to make the House Appropriations Committee Members understand that the funding established in the Subcommittee for The National Institutes of Health (NIH) and The National Cancer Institute (NCI) are not sufficient to continue our fight against cancer.

As I approached the Committee Room I was pleasantly surprised to see the sign on the door that said, “LHHS Mark-Up postponed.” What does this mean for us? This gives us a chance to rally the troops and reach out to the Appropriations Committee Members’ Offices with our message.

Let them know that 1.9% increase for NIH and 1.5% increase to NCI are some of the worst numbers we have seen in years and are not adequate to fight this war against cancer!!

The message is simple:
• Over 52,000 people will die from colorectal cancer in 2007 alone.
• 186 members of the House of Representatives signed a letter in support of a 6.7% increase for NIH.
• Failure to provide adequate funding will stall the next generation of breakthroughs for cancer patients. The current bill proposed in the House would do just that.

TAKE ACTION TODAY!!

For a listing of Committee Members and their phone numbers, click here (PDF file)