Update for Patients on FOLFOX Using Calcium/Magnesium for Neurotoxic Side Effects

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.

Posted by Nancy Roach on August 3rd, 2007
Posted in: Research & Treatment News | 1 Comment »

CMS issues decision on coverage of Erythropoiesis Stimulating Agents (ESAs), C3 Cited in Ruling

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.

Continue reading…

Posted by Judi Sohn on August 1st, 2007
Posted in: Research & Treatment News | 2 Comments »