Fight Colorectal Cancer

Tony Snow, White House Press Secretary, speaks to David Gregory from MSNBC about living with colorectal cancer.

Click here to watch this interview.

While obesity is a known risk factor for polyps that can progress to colon or rectal cancer, researchers have found that it also increases the risk that more polyps will occur.  Men whose body mass index (BMI) was over 30 were about one third more likely to have a new polyp (adenoma) three years after previous polyps were removed.

There was no similar effect in women.

Risk of an advanced adenoma was also higher.  The highest increase of all was for obese men or women who had a family history of colorectal cancer.  They had more than twice the chance of developing a new polyps during the average 3 year follow-up time.

Odds ratios for developing additional polyps with BMI higher than 30:

• Overall men and women:  1.17 or 17%, which wasn’t significant.
• Women: 0.90
• Men: 1.36 or 36% higher risk
• Non-advanced polyps in men: 1.26
• Advanced polyps in men: 1.62
• Men and women with no family history: 1.00   (no change in risk)
• Men and women with a family history: 2.25

Elizabeth Jacobs Ph.D. and her colleagues at the University of Arizona at Tucson concluded,

Our results support obesity as a risk factor for subsequent short-interval (mean follow-up time 3.1 years) development of colorectal adenomas, particularly among men and persons with a family history of colorectal cancer. Furthermore, obesity in men appears to be strongly associated with the development of clinically advanced lesions.

SOURCE: Jacobs et. al. Clinical Gastroenterology and Hepatology, Volume 5, Issue 8, Pages 982-990, August 2007

In a phase II study of patients with previously untreated colorectal cancer, doctors added Tarceva® (erlotinib) to standard FOLFOX plus Avastin® treatment.

Tarceva blocks epidermal growth factor (EGFR) pathways in the cancer cell reducing its ability to divide and grow.  Avastin (bevacizumab) acts on other cellular pathways reducing the ability of the tumor to develop a blood supply. Scientists thought that attacking both pathways at the same might shrink tumors and increase the time until the cancer began growing (progression).

However, none of the 35 enrolled patients were able to remain in the trial until cancer progression.  More than half were removed from the study because of adverse events, another 25 percent asked to stop the treatment because the side effects were too difficult to tolerate.  Overall 86 percent of patients had at least one grade three or four adverse event.

Serious side effects included rash, neuropathy, and diarrhea.

About a third of patients had some tumor shrinkage during the trial, but the effectiveness of the treatment could not be fully assessed because of the high number of study withdrawals.

Concluding, J.A. Meyerhardt M.D.and colleagues wrote,

The combination of FOLFOX, bevacizumab and erlotinib led to higher than expected early withdrawal due to toxicity, limiting conclusions regarding efficacy. These findings raise concern regarding the tolerability of adding more agents to already complex combination regimens for metastatic colorectal cancer.

Preliminary information from the study was presented at ASCO 2006 by Dr. Meyerhardt.

SOURCE: Meyerhardt et al. Annals of Oncology, Volume 18, Number 7, Pages 1185-1189, July 2007.

As reported in a C3 post on June 26, a phase IV clinical trial* was closed after an interim analysis indicated that the use of calcium/magnesium to reduce neuropathy caused by FOLFOX might also reduce the effectiveness of this chemotherapy treatment.

In this trial*, patients receiving FOLFOX and bevacizumab chemotherapy were also randomized to Magnesium Sulfate and Calcium Gluconate before and after oxaliplatin in a double-blind placebo controlled fashion.  The preliminary data from the first 174 patients on the trial showed that patients who had received calcium/magnesium had significantly less tumor shrinkage than patients who did not receive calcium/magnesium.  The data is based on scans of patients’ tumors.

As a result, the trial was closed and all patients on the trial will receive future treatment without calcium/magnesium.

The data will be verified as follows:

• An independent committee of expert radiologists is being convened;
• The committee will examine all scans from the trial. Their examination will be blinded (they will not know which patients received which treatment); and
• The results of their examinations will be analyzed, and compared to the preliminary data.

The verification process is expected to take several months.  Final results may be available in early 2008.

On July 31, the Journal of Clinical Oncology published a letter from the trial’s primary investigators.  The investigators say the following:

At present, bearing in mind the preliminary and unconfirmed nature of these data, we would like our colleagues to be aware of this unexpected finding. Oncologists should recognize the possibility that calcium and magnesium may reduce the activity of FOLFOX and bevacizumab in the treatment of colorectal cancer and exercise appropriate clinical judgment when using these agents in the neuroprotective setting until definitive data are available. For the time being, we would urge that calcium and magnesium salts particularly be avoided in the adjuvant setting, where reduced efficacy could lead to reduced benefit, and be reserved for those with symptomatic acute neurotoxicity.

Full letter text available here. 

C3 asked sanofi-aventis (the manufacturer of oxaliplatin) how this information was being disseminated to the oncology community. Sanofi-aventis indicated that its sales force was carrying the information to oncologists and oncology nurses, and that these efforts would continue.

WHAT THIS MEANS TO PATIENTS:
If you are receiving calcium-magnesium as treatment for neuropathy related to your FOLFOX regimen, talk to your doctor to be sure that s/he is aware of this preliminary data.  If your doctor is unaware, s/he can contact sanofi-aventis Medical Information Service at 1-800-633-1610 option 1 for additional information.

While this data is preliminary, patients and doctors should take it into account when planning treatment.

Source:
Sanofi-aventis website
Hochster et al, Journal of Clinical Oncology, July 31 2007

* CONCEPT Trial – a Phase IV, Randomized, Prospective Multicenter comparison of an Intermittent Schedule of Oxaliplatin combined with 5-Fluorouracil/Leucovorin (FOLFOX) / Bevacizumab Versus the Conventional Mode of Administration of FOLFOX/Bevacizumab PLUS Neuroprophylaxis With Calcium/Magnesium for the Optimization of First-Line Therapy of Metastatic Colorectal Cancer.  Available here.

Disclosure: C3 has accepted funding for projects and educational programs from sanofi-aventis in the form of charitable donations. C3 has ultimate authority over website content.

By Carlea Bauman, Executive Director

In May 2007, the Centers for Medicare and Medicaid Services (CMS) announced a proposal to discontinue coverage for Erythropoiesis Stimulating Agents (ESAs), a type of drug that plays a big role for some with colorectal cancer. See “Proposed Decision Memo for Erythropoiesis Stimulating Agents (ESAs) for non-renal disease indications (CAG-00383N)”.

ESAs, better known under brand names, Procrit, Epogen and Aranesp, were approved by the Food and Drug Administration (FDA) to aid with chemotherapy-induced anemia.

C3 was concerned about several aspects of the proposed ruling and submitted comments to CMS on June 13, 2007. This past Monday, July 30th, CMS issued its final ruling on ESA coverage.

The concerns raised by C3 made a difference for the thousands of Americans who rely on Medicare for their colorectal cancer care. Every issue we raised in our comments impacted CMS’s final decision.

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