Personalized medicine is what the cancer community calls treatments that are tailored to each patient’s genetic makeup. It is the future of cancer care and in some cases, it is already making a big difference in the ways patients are treated.

You can learn about these cutting edge treatments and about emerging findings in an archive of the webinar below.

Our thanks to Carolyn Grande, CRNP, AOCNP for leading the discussion. She a phenomenal educator on this topic and a member of our Medical Advisory Board. She graciously donated her time to bring this information to patients.

Medicine that is tailored to each patient’s genetic makeup is the future of cancer care. In some cases, it is already making a big difference in the ways patients are treated. Learn about these cutting edge treatments and about emerging findings that will be important for future diagnoses and treatments of colorectal cancer. Discussion led by Carolyn Grande, CRNP, AOCNP.

The latest news from the petri dish
Wednesday, April 20, 2011
8 – 9 PM Eastern

Dr. Yaeger at work in her lab

Dr. Rona Yaeger will discuss the research she has been conducting over the past year with the grant she received as part of Fight Colorectal Cancer’s Lisa Fund research program.

Dr. Yaeger’s research focused on inhibiting the AKT pathway in colorectal cancer cells. She conducted basic research to determine how inhibitors to the pathway might affect cells of patients who have mutated KRAS and are resistant to EGFR inhibiting drugs. Dr. Yaeger has also been conducting a phase II clinical trial with an AKT inhibitor for patients with metastatic colorectal cancer who have normal (wild type) KRAS.

If you are interested in learning more about the future of cancer treatments, or if you’ve ever donated to the Fight Colorectal Cancer Lisa Fund, do not miss this webinar!

Personalizing personalized medicine
Monday, April 25, 2011
8 – 9 PM Eastern

Carolyn Grande, CRNP, AOCNP

Oncology nurse practitioner Carolyn Grande will make personalized medicine a little more personal during this webinar. If you’ve ever heard your doctor mention “tumor markers,” “biomarkers,” “KRAS”, “BRAF,” or “tumor pathways” and wondered what he or she meant, this webinar is for you. In fact, Carolyn may even be able to explain why Rona Yaeger’s pathway research (above) could mean big answers for colorectal cancer patients some day.

Carolyn is a member of Fight Colorectal Cancer’s Medical Advisory Board. In March, she presented this information to the advocates who participated in our Call-on Congress. Her presentation was so popular, we asked and she graciously agreed to make it a part of our webinar program. Don’t miss out!

Treating liver mets
Monday, May 16, 2011
8 – 9 PM Eastern

Dr. Andrew Kennedy

The liver is usually the first place where colorectal cancer metastasizes, so learning to manage tumors in the liver can help stage IV patients survive longer. Fortunately, liver directed therapies have evolved over the last two decades so patients with metastatic or primary liver tumors now have many new treatment options.

We are pleased that one of the leading researchers on liver metastases in the country has agreed to speak about these new options with us and our webinar participants. Join Dr. Andrew Kennedy and learn about how you may be impacted by these new discoveries. Register today.

Don’t worry if you’ve missed some of our webinars.

We archive them! You can watch and listen to the following patient webinars any time (in descending chronological order):

Last year at ASCO, Dr. Daniel Sargent presented new data that patients with stage II disease with microsatellite instability do not only not benefit from 5-FU, but they may be harmed, and it was recommended to test for MSI in all stage II colon cancer patients and in the presence of MSI-high not to give 5-FU. For stage III colon cancer that was not the case.

This year, the PETACC-3 clinical trial was analyzed for MSI and did not show the same the same findings. It seems that chemotherapy does not harm these patients, and they may benefit.

This has been an ongoing controversy over the last couple of years with some studies showing benefit and other not. Last year’s ASCO showed there even may be harm.  What MSI means is now again up in the air. We can certainly state that the presence of MSI is a GOOD prognostic marker, meaning that these patients have a lower risk of tumor recurrence. However, if chemotherapy is beneficial or not is still not clearly answered.

Another finding in this clinical trial showed that 18q deletions are not prognostic in stage II disease when MSI status is known. That is important because our clinical trial E-5202 in the US assumed that patients with an 18q deletion are at higher risk for tumor recurrence independent of MSI, which may alter the interpretation of the clinical trial.

All these data show that we are learning a tremendous amount about the molecular make up of tumors, but it also shows that it is not easy to develop clinically meaningful markers. However, there is no doubt that new markers will be identified and validated over the years to come and will make our personalized oncology care a reality.

This was the clinical trial testing whether the addition of Avastin to FOLFOX would increase efficacy in reducing recurrence for patients with stage II and III colon cancer.  FOLFOX was given over 6 months compared to FOLFOX in combination with Avastin for 6 months, followed by additional 6 months of Avastin. There was a great hope that this anti-VEGF therapy would further decrease tumor recurrence.

This is a little bit surprising, since the addition of Avastin increased efficacy of many therapies for different cancers including lung, breast, colon and head and neck cancer. However looking closer in colon cancer, a recent company-sponsored study showed that the addition of Avastin did not increase response rates and did not increase progression free survival when combined with FOLFOX and there was no overall survival benefit. Therefore, it may be this combination is not as effective as we hoped for.

The exact details of the clinical trial will be reported at the Annual Meeting of the American Society of Clinical Oncology in Orlando in May 2009. This is the largest oncology meeting in the world with more than 25,000 oncologists attending from around the world. This meeting reports the newest data and sets new standards for the treatment for patients with cancer.

This is another lesson we have learned that the treatments we use for patients with metastatic colon cancer can not always be translated into benefits in the adjuvant setting. Our own group will present data at ASCO on how to predict efficacy of FOLFOX/Avastin in patients with metastatic disease. We found gene expression levels of genes involved in the DNA repair and in different growth pathways make a difference in response to Avastin and FOLFOX.

In the future we need to select patients who really benefit from chemotherapy by testing tumors for sensitivity. We have made a great progress with testing for KRAS but this is only the beginning. We have some preliminary data showing in addition to MSI and 18q deletion that will recur after successful surgery and being treated with adjuvant chemotherapy.

There is one other big trial in adjuvant chemotherapy ongoing, N0147, which is using Erbitux instead of Avastin. We are eagerly waiting to see whether this combination will be more successful.

Despite this negative Avastin trial, the future for colon cancer therapies is looking very promising with novel drugs being developed and new genetic advances which help us to tailor chemotherapy to increase efficacy and decrease toxicity.

I am trying to change the way we treat patients with colon or rectal cancer. Over the last 10 years we have identified genetic signatures which help us choose the most effective and least toxic chemotherapy. In my practice every patient with newly diagnosed colon cancer is genetically tested for KRAS and two genes which show whether FOLFOX chemotherapy is more likely to be successful.

Today when a patient walks in with metastatic disease only in their liver, we think about a possible cure depending on number, size and location of those metastases. It is important to choose the most effective therapy since that can be the difference of a chance of curative resection or not.

Our patients at the University of Southern California (USC) have been incredibly supportive in donating their blood and tissues for our research. Our expertise in this area also is essential to understand to develop new drugs. When you know why tumors grow and escape chemotherapy, you may be able to develop a novel drug to attack  cancer more effectively. That is exactly what we are doing.

Not only our patients but foundations and private donors are helping us to change the way colorectal cancer patients will be treated in the future. Our goal is to cure more and more patients by developing better drugs. Two foundations, the Dhont Foundation and the San Pedro Guild in San Pedro, California, have supported us in the past. With their help, our research group was the first to identify critical genes for new drug development.  Based on our findings we have started to develop our own drugs.

There is no doubt that in a couple of years, every patient undergoing chemotherapy will be tested to select the most effective and least toxic therapy. We will make sure this will happen sooner than later.

Scientists analyzed nearly 400 tumor samples from patients with colorectal cancer for changes in the KRAS gene.  The patients were part of a randomized study that compared treatment with Erbitux alone (monotherapy) to the best supportive care.  Patients had all been previously treated with 5FU or Xeloda® (capecitabine), Eloxatin® (oxaliplatin), and Camptosar® (irinotecan) and had their cancer get worse.

Mutations in the KRAS gene were found in more than 43 percent of tumors.

Among patients with normal or wild-type KRAS, there were significant differences between those who received Erbitux and those who didn’t:

• Median overall survival time increased from 4.8 months to 9.5 months.
• Median time before cancer got worse or progressed increased from 1.9 months to 3.7 months.

However, for patients with mutated KRAS there was no difference in time until cancer progressed or overall survival time with Erbitux treatment.

In the group of patients who were receiving supportive care, but not Erbitux, there was no difference in survival between those with KRAS mutations or wild-type KRAS.

Christos S. Karpetis and his colleagues concluded,

Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab.The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone.

Speaking to HealthDay News, Dr. Karapetis said,

We believe that, in the context of pre-treated advanced bowel cancer, the K-ras mutation status of the cancer should be determined before using cetuximab, and cetuximab should only be given to patients with tumors that do not have the mutation.

This study has been previously reported at medical conferences, but its publication in the peer-reviewed New England Journal of Medicine adds strength to its conclusions.

The entire study that showed Erbitux to be superior to best supportive care in advanced colorectal cancer that had progressed on standard treatments was published last year in the New England Journal of Medicine.

You can find additional information about KRAS mutations and treatment with EGFR inhibitors Erbitux and Vectibix on the C3 website.

SOURCE: Karapetis et al.,New England Journal of Medicine, Volume 359, Number 17, October 23, 2008.

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

Italian researchers measured magnesium levels for 68 patients before treatment began and then 6 hours, 1 7, 14, 21, 50, and 92 days later.  After the seventh day, readings decreased consistently.

Magnesium levels fell at least 20 percent for 25 patients by the third week.  More of these patients responded to treatment, they lived longer before their cancer got worse and had longer overall survival.

Response rates for patients with an early reduction in magnesium were 64 percent,  compared to 25.6 percent of other patients.

Median time to progression for the early hypomagnesemia group was 6 months compared to 3.6 months for those whose magnesium levels fell more slowly.  Overall survival was 10.7 months versus 8.9 months.

Measuring magnesium may provide a way to predict whether or not Erbitux will be successful in treating advanced colorectal cancer.

Bruno Vincenzi and colleagues wrote,

Our results confirm that cetuximab treatment may induce a reduction of Mg²⁺ circulating levels and offer the first evidence that Mg²⁺ reduction may represent a new predictive factor of efficacy in advanced colorectal cancer patients treated with cetuximab plus irinotecan.

SOURCE: Vincenzi et al., Clinical Cancer Research, Volume 14, Number 13, July 1, 2008.