'Off label' use worries Gleevec researchers

Doctors conducting clinical trials of Gleevec on GIST patients say they are worried that oncologists will try the drug on the wrong patients.

Dr. Charles Blanke of Oregon Health Sciences University, and Dr. Allan T. van Oosterom, professor of medicine at the University of Leuven in Belgium and president of the European Organization for Research and Treatment of Cancer (EORTC), voiced their concerns to WebMD (www.webmd.com).

While the drug is approved for leukemia and "demonstrated efficacy in GIST," Gleevec is a targeted therapy that only works if the target is present. In solid tumors, that means that the tumor must test positive for the very specific biological mechanisms.

Patient advocates told the San Francisco Chronicle that many people with terminal disease would opt simply to pressure their doctor for a prescription.

"Once word gets out, there'll be a line out the door," the Chronicle quoted Victoria Colgan, a lung cancer survivor who was helping staff the Alliance for Lung Cancer Advocacy Support and Education booth at the American Society of Clinical Oncology conference in San Francisco.

The Chronicle also reported that the Kidney Cancer Association has been deluged with calls from patients who have heard about Gleevec's success against chronic myeloid leukemia, said Carl Dixon, president and executive director. He told the Chronicle that while Gleevec isn't designed to fight kidney cancer, this doesn't always deter people who are desperate.

"I'm sure that people are going to seek it out and that some docs will experiment with prescribing it," Dixon was quoted as saying. "If you have a patient and you have nothing else to offer, why wouldn't you?"

Now that FDA has approved Gleevec for CML, doctors are free to prescribe the drug to any cancer patient, on a so-called "off label" basis.

That worries doctors involved in the clinical trials. Van Oosterom told the Chronicle that any doctor who prescribes the drug outside of approved uses is "irresponsible."

"I don't think anyone should have this drug without proper testing," he said.

Similar concerns were voiced by Dr. Brian Druker, director of the Leukemia Center at OHSU and co-developer of Gleevec. "When we developed this compound (in conjunction with Novartis), we knew it was specific enough to have limited toxicity but also might target more than one protein."

CML, GIST and the brain cancer glioblastoma are each driven by a single enzyme. Gleevec can disable these three enzymes, which are similar in structure. But most other cancers are more complicated, say the scientists, with multiple abnormalities working in concert.

"Those enzymes may be present in those cancers, but ‘present’ doesn’t necessarily mean critical to the cancers’ growth or survival," says Druker. Locking up one troublemaker in a chemically complex cancer wouldn’t create a response.

"It would be the difference between cutting off a finger," Druker says, "and putting a stake through the cancer’s heart.”