FDA Approves Fusilev for Colorectal Cancer

Advanced colorectal cancer is now an FDA approved indication for Fusilev® (levoleucovorin) in combination with 5-FU.

According to a news release from its manufacturer, Spectrum Pharmaceuticals, the FDA agreed to include metastatic colorectal cancer on the Fusilev label on April 29, 2011.

Although Fusilev has been used off-label during the leucovorin shortage, it is now fully FDA-approved for the palliative treatment of advanced colorectal cancer that has spread beyond the colon or rectum.

So what’s the difference?

Leucovorin is a racemate compound.  Its molecule has two chemical compounds that are exact mirror images of each other, one active and one inactive.  Fusilev (levoleucovorin) contains only the active part of the racemic leucovorin molecule.

It is critical that physicians and pharmacists realize that dosing for leucovorin and Fusilev are not the same. Only one half the dose of leucovorin should be given when Fusilev is used to replace racemic leucovorin.

Is Fusilev more effective?

A number of studies have found no difference between leucovorin and levoleucovorin in combination with 5-FU or alone for cancers in the gastrointestinal  tract.  Two randomized clinical trials direct compared the two:  uncovering no differences in effect on tumor shrinkage, time until cancer got worse, survival time, or the percentage of patients who were alive one and two years after beginning treatment.

In 2009 researchers at Georgetown reviewed all the published studies of the use of levoleucovorin in gastrointestinal malignancies to assess whether levoleucovorin is a reasonable alternative to racemic leucovorin.  They concluded,

In many studies of patients with gastrointestinal malignancies, levoleucovorin has been used interchangeably and solely for racemic leucovorin for 5-FU modulation. Our literature review demonstrates that levoleucovorin has similar efficacy and tolerability when compared with racemic leucovorin, whether used in combination with other chemotherapeutic agents or alone.

What about costs?

Fusilev is many times the cost of generic leucovorin, and Medicare and some insurances have been paying only a part of that cost up until now.  Medicare reimburses oncology practices $750 for a dose of Fusilev, with the full cost of up to $1,200 being absorbed by some practices during the leucovorin shortage.

With FDA approval for the metastatic colorectal cancer indication, Medicare can now reimburse the full cost.

What’s the impact of the FDA decision for doctors and patients

Since 2008 there have been continuing shortages of leucovorin, which enhances the effectiveness of of 5-FU (fluorouracil).  As of April this year, there were still serious problems obtaining leucovorin to treat people with colorectal cancer.

On April 19, 2011 the American Society of Health-System Pharmacists reported that leucovorin shortages continue without any expected dates when they will end.  At the same time there is increased pressure on Fusilev, and Spectrum is also reporting shortages of it.  The FDA has inspected an Italian Pfizer manufacturing facility and has approved  temporary Fusilev imports from that facility only.

Doctors may choose to avoid risking leucovorin shortages and turn to Fusilev for their patients with advanced colorectal cancer if reimbursement is not a problem.

Hopefully, patient anxiety will be reduced, and standard treatment for colorectal cancer will  be available in the United States.

SOURCES: Kovoor et al., Clinical Colorectal Cancer, Volume 8, Number 4, October 2009.

Fusilev image courtesy of Monthly Prescribing Reference.






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