French scientists have validated a previous study that showed patients with a mutation in a the KRAS gene have little or no response to Erbitux (cetuximab).

The current research studied 89 patients who received Erbitux® after treatment with Camptosar® (irinotecan) had failed.  Some were treated with Erbitux alone, some with a combination of Erbitux and Camptosar.

A KRAS mutation was present in about 30 percent of patients.  Comparing those patients with the group that did not have changes in the KRAS gene, the researchers found:

• No reduction in the size of tumors (response) in the KRAS-mutated group versus a response to treatment that reduced tumor size in 40 percent of the non-mutated patients.
• Shorter time to tumors growing or appearing in new places (time to progression):  10.1 weeks in the KRAS-mutated group versus 31.4 weeks in the others.
• Shorter overall survival: 10.1 versus 14.3 months.

Severe skin rash has also been previously shown associated with survival after Erbitux treatment.  The French team pooled the 89 patients in this study with their previous 30 patients to compare KRAS mutation to skin rash.  While severe skin rash did predict longer overall survival independently, it was not a factor in either response to treatment or progression free survival.

Looking at the two favorable predictors of overall survival (severe skin rash and lack of a KRAS mutation) they found that median survival time was:

• Two predictors (severe rash and no KRAS mutation) 15.6 months.
• One predictor: (severe rash or no KRAS mutation) 10.7 months
• No predictors: (KRAS mutation without severe rash) 5.6 months

Writing about the importance of identifying those patients who will actually benefit from treatment with Erbitux, the authors said,

It is necessary to better define the subpopulation of patients who truly benefit from cetuximab because cetuximab is associated with an increase in treatment costs, frequent trips to therapeutic centers, and specific toxicity. Therefore, the identification of markers
allowing the selection of patients who are likely to benefit from this novel targeted therapy is an important challenge

Although Erbitux inhibits the activity of EGFR (epidermal growth factor receptors) on the surface of cancer cells reducing their ability to divide and grow, measurement of the level of EGFR in tumors using a common immunohistochemical test has not shown that lack of EGFR in tumors limits response to Erbitux.  Patients whose tests show no EGFR can still respond to and benefit from treatment with Erbitux.

However, the current study, along with the previous one, show that testing tumors for a mutated KRAS gene does predict response, time to progression, and overall survival.  It is a test that can be done before beginning treatment and can save patients from the cost and toxicity of a therapy that won’t benefit them.

The research team, led by Astrid Lievre, concluded,

These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.

SOURCE: Lievre et al. Journal of Clinical Oncology, Volume 26, Number 3, January 20, 2008.

Previously, C3 News and Events carried a story about the earlier research.

Disclosure: C3 has accepted funding for projects and educational programs from Bristol Myers Squibb in the form of unrestricted educational grants. C3 has ultimate authority over website content.

It was a busy weekend for all the Presidential candidates. With primaries in Nevada and South Carolina happening on Saturday, the race for the White House continues to heat up.

Mitt Romney and Senator Hilary Clinton came out on top in Nevada, while Senator John McCain took the top spot in South Carolina.

Romney, who won the Nevada primary by more than 40 percent, was very visible this week campaigning in the western state while his fellow Republicans spent most of their time in South Carolina.

The Clinton and Obama camps continued trading shots with each other on Saturday. Both campaigns were making claims of vote suppression, with former President Clinton claiming to see it firsthand.

The drama continues with Democrats heading to South Carolina and Republicans on their way to Florida.

Click here to check out CNN’s “Election Center”

Dr. Judah Folkman, pioneering cancer researcher who first developed the theory that cancer needs new blood vessels to develop, died suddenly on Monday, January 15, 2008 of a heart attack. He was traveling to a speaking engagement in Vancouver.

Folkman’s research into angiogenesis was initially dismissed with skepticism.  He first published his ideas in 1971 in the New England Journal of Medicine but they were poorly accepted by doctors who saw the future of cancer treatment in destroying cancer directly through surgery or chemotherapy.

His laboratory developed two drugs that targeted blood vessel development — endostatin and angiostatin — but neither was eventually approved for cancer treatment in the United States.  However, endostatin is widely used in China.

In 1998 when reports that tumors were dramatically shrinking in mice treated with anti-angiogenic drugs in Dr. Folkman’s laboratory, there was great excitement and speculation that the cure of cancer was on the immediate horizon.  That proved premature.

In 2004 Avastin® (bevacizumab) was approved by the FDA to be used with chemotherapy to treat colorectal cancer.  Avastin blocks VEGF — vascular endothelial growth factor — to prevent the development of a healthy blood supply for tumor growth.  Today nearly 30 other agents are in use or are being developed that also target tumor blood supply.

Interviewed for the PBS Nova program  Cancer Warrior, Dr. Folkman talked about the fine line between persistence and obstinacy in science.  The entire Cancer Warrior program can also be seen online.

His friend, Dr. James Mandell, the CEO of Children’s Hospital in Boston told Newsweek that Folkman was the person who “never gave up. He was always the person who said,”

What are the problems you see in the patients? What are the unanswered questions? Let’s take them back to the lab and figure them out.

Last year, I had the special privilege of hearing Dr. Folkman’s Centennial lecture at the American Association for Cancer Research annual meeting in Los Angeles.  You can see his slides and hear Dr. Folkman’s talk on the AACR webcasts. Early in the morning — it was a Sunrise Session — Folkman was full of energy and humor.  He talked about the future of anti-angiogenic agents and the hope that treatments would be found to deal with the entire complex network of angiogenesis.

He also described the patients from whom he learned and talked about science and his young granddaughter.

His courage and willingness to keep on working despite controversy and skepticism is an inspiration to both researchers and advocates.  He will be greatly missed.

In an interview with the Boston Globe last November, Folkman summed up much of both the dreams and frustrations of cancer researchers when he said,

The ideas are simple, but getting them figured out is very complicated.   We never use the word ‘cure’ because it is far away,It may be that patients will have little tiny cancers that lie dormant for a long time.

Folkman was born February 24, 1933 in Cleveland, Ohio.  At the time of his death he was Professor of Cell Biology at Harvard and director of the Vascular Biology Program at Children’s Hospital in Boston.  He is survived by his wife Paula, two daughters, and a granddaughter.

Mitt Romney claimed victory in the Michigan Republican primary on Tuesday. This is the first major win in his 2008 run for President.

Some political analysts said Michigan was a must-win for Romney, who finished second in Iowa and New Hampshire (CNN).

Senator Hilary Clinton (D-NY) also came out on top in Michigan. Clinton was the only Democratic front runner on the ballot. Democratic Party officials decided to strip Michigan of its delegates for its decision to schedule their primary so early.

Top Democrats had their names removed from the ballots in camaraderie with their party. Party leaders urged supporters of Senators Barack Obama and John Edwards to vote “uncommitted” in the primary. Under state law supporters of the other top candidates cannot cast write in votes for them.

The saga continues.

Still smarting from the partisan wars of 2007, Congress confronts a sinking economy, a lingering war and election-year politics as it gets back to work for the 2008 session…Click here to read more