Cheap diabetes drug tested as cancer treatment

Can a cancer patient be cured for 42 cents a day? That’s what Canadian researchers will find out in a massive study featuring a half-century-old drug, more than 3,000 breast-cancer patients and an oncologist who kept pushing when no brand-name drug company was interested.

The clinical trial – to probe whether a diabetic drug can stop breast cancer from returning – will start enrolling patients across the country as early as July, about five years after Pamela Goodwin, who holds the Marvelle Koffler chair in breast research at Mount Sinai Hospital in Toronto, tried to get it funded.

“The implications are potentially huge,” said Dr. Goodwin, a University of Toronto professor of medicine.

If it turns out this old drug has a new use, lives could be saved for pennies a day. And yet cost-effectiveness is precisely why it took so long to get the study funded: with no high-priced patented drug to sell after the trial was completed – cancer drugs typically retail for $50,000 per patient a year or more – no pharmaceutical company would fund it.

Dr. Goodwin was told as much after having “very, very exciting conversations” five years ago with a multinational drug company that made the drug metformin hydrochloride.

“They went to their international headquarters and came back to us and said: ‘We can’t do it. It will be off patent,’ ” she recalled, declining to identify the drug company. (When drugs come off patent, the medication can be made by many companies and is sold for a fraction of the price.)

Metformin is the number one drug prescribed to those with type 2 or adult-onset diabetes, with 10 million prescriptions filled last year at a retail value of $220-million, according to figures from IMS Health Canada, a private company that tracks prescription drug sales.

It gained interest as a cancer drug after researchers discovered women with insulin levels in the higher range of normal had more breast cancer recurrences and higher death rates. Dr. Goodwin and others looked on the shelf for a drug to lower insulin – Metformin the best-known drug for diabetes, also happened to have the fewest side effects.

“If recurrence is in any way related to increased insulin levels, [metformin] may help as many as three-quarters of patients, if not more,” said Ontario Cancer Institute scientist Vuk Stambolic, who is leading the basic science aspect of the trial with Dr. Goodwin. His work focuses on molecular pathways regulated by insulin and metformin.

Breast cancer patient Wendy Sexsmith, 56, certainly hopes that is the case. She took the drug twice daily last summer for three weeks as part of a smaller study before undergoing her breast conserving surgery. After the operation, scientists dissected her tumour to see if the drug changed her biology. She is awaiting results.

“I was on it at a time when they were fairly certain it had some anti-tumour impact,” said Ms. Sexsmith. “I just thought to myself, ‘I can’t really lose here.’”

The trial is expected to include 3,582 patients in Canada and the United States who are undergoing standard cancer treatment plus metformin or placebo for up to five years. Until the results are in, Dr. Goodwin stressed that patients should not use it unless it is prescribed for diabetes or they are on the clinical trial, where they can be properly monitored.

Each tablet costs 21 cents and must be taken twice daily. Despite the low price, the cost to run such a clinical trial, which involves collecting blood samples, is expected to run at least $15-million.

Dr. Goodwin received up to $3-million from the NCIC clinical trials group, funded by the Canadian Cancer Society about 18 months ago. The National Cancer Institute in the United States offered $8-million and the New-York-based Breast Cancer Research Foundation is picking up the cost of drug distribution.

But Dr. Goodwin still had to find a company to provide her with the drug, plus a sugar pill that would act as a placebo. She contacted Barry Sherman, chairman and chief executive officer of Toronto-based Apotex, one of the largest producers of generic drugs. One 15-minute phone conversation was all it took for him to agree to provide both the drug and the placebo.

“We’re not doing this to show metformin doesn’t work” said Ralph Meyer, director of the NCIC clinical trials group. “We’re very hopeful our hypothesis will prove true and … will be a very important therapy at a worldwide level.”

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Lisa Priest

From Wednesday’s Globe and Mail