An advisory has been issued after the colorectal cancer drug Avastin was linked to the development of a rare, potentially fatal problem with the esophagus.

Health Canada approved the use of Avastin or bevacizumab, in combination with other drugs, to extend the lives of people with colorectal cancer that has spread to other sites.

In an advisory Tuesday, the department said use of Avastin and other cancer treatments has been linked with the development of tracheo-esophageal fistulas — abnormal connections between the esophagus (the tube from the throat to stomach) and the trachea (the windpipe), which normally remain separate.

Fistulas developed in two patients with small cell lung cancer who were treated with Avastin, other cancer drugs and radiation as part of a clinical trial in the U.S.

One patient died. Another death was also reported, and a TE fistula is suspected but not confirmed in that case.

"A direct cause and effect between Avastin and these events has not been established, but cannot be ruled out," Health Canada said. 

"Avastin should no longer be given to patients who develop a TE fistula," the public advisory said.

No Canadian patients were enrolled in the U.S. study, and to date, no cases of TE fistula have been reported in Canada, the department said in its advisory to health-care professionals.

Prescribing information for Avastin will be updated to include more on the fistula link, and the drug's manufacturer, Hoffmann-La Roche Limited, has sent a letter to health-care professionals to inform them of the new safety information.

Signs and symptoms of TE fistula include:

• Chest pain, shortness of breath, wheezing or laboured breathing.
• Coughing or choking when eating or drinking.
• Coughing up food or liquids.
• Wheezing sounds following every breath.

Anyone who develops any of these signs or symptoms should contact their doctor or health-care professional immediately, Health Canada advised.

Avastin works by stopping the blood supply to cancerous tumours.

It is not approved for use in Canada for cancers other than colorectal, but it is being tested as an experimental drug for prostate, kidney, pancreatic and ovarian cancer.

As of March 22, 2007, six additional cases of TE fistula have also been reported worldwide in other lung and esophageal cancer studies involving the use of Avastin and chemotherapy alone or along with radiation.