Actos Bladder Cancer: The Meaning Behind 'Maybe'

Washington, DCWhen the US Food and Drug Administration (FDA) issued its safety announcement with regard to Actos and bladder cancer last June, the agency made liberal use of the word 'may' when describing the possible association with an increased risk of bladder cancer following use of pioglitazone (Actos) for longer than one year.

The association may be there. It might be there. To paraphrase the FDA, 'maybe' there is an association.

And yet other countries have either restricted use of Actos to existing patients only, or have pulled pioglitazone from the market altogether. And a study published this past spring in the respected British Medical Journal (5/31/12) concluded, "The use of pioglitazone is associated with an increased risk of incident bladder cancer among people with type 2 diabetes."

One study does not warrant a conclusive determination on the subject product. However, it does offer perspective. The retrospective cohort study based on a nested case-control analysis utilized data contributed by 600 general practices in the UK. And the study authors concluded that there IS increased risk for bladder cancer associated with use of Actos.

Risk itself is an abstract. Thus, even an increase in risk suggests that the possibility remains the patient will not develop Actos bladder cancer. It's just that the possibility is increased for Actos patients over those who do not take Actos.

The FDA, however, in the agency's safety warning issued in June, 2011 appeared to take the softest possible stance when it stated "use of the diabetes medication Actos (pioglitazone) for more than one year may be associated with an increased risk of bladder cancer."

According to the cautionary statement, the FDA reviewed data from a planned five-year interim analysis of an ongoing, ten-year epidemiological study. According to the agency the five-year results showed that although there was no overall increased risk of bladder cancer with Actos use, an increased risk of bladder cancer was noted among patients with the longest exposure to pioglitazone, and in those exposed to the highest cumulative dose of pioglitazone.

Hence, the FDA's position on Actos use for a period of one year or longer. The FDA also noted the epidemiological study in France that also found an increased risk of Actos bladder cancer. France has since banned the use of Actos outright, while Germany is the country that is suggesting Actos should not be started in new patients.

And yet, even with the observation that a risk for Actos bladder cancer was noted among patients with the longest exposure to Actos??"and even given the fact that 'risk' is a subjective term anyway??"the FDA was not prepared, in its opening statement, to state that there was an increased risk of these Actos side effects.

Only that there 'may' be an increased risk.

Maybe. Perhaps. Possibly.

Is the FDA simply soft? Or is it trying to save face after approving a drug that now appears to have grievous Actos side effects in some people? Type 2 diabetes takes up a fairly significant footprint on the American landscape with, according to the FDA's own figures, no fewer than 2.3 million people filling prescriptions for Actos in the ten months ending October, 2010.

Many of those Actos patients would have been switched from Avandia after fears associated with a high risk for Avandia heart attack. Perhaps the FDA is trying to soften the blow to those 2.3 million Americans, by using the softest language possible.

Or perhaps the FDA finds itself caught between a rock and a hard place. Type 2 diabetes is an ongoing condition that rarely disappears once it emerges. Therefore, diabetes patients require ongoing therapy to manage and control blood sugar levels. Certainly, for the vast majority, for far longer periods than just a year.

Actos was touted as a much safer alternative to Avandia. That position now appears to be suspect. The question now, for any patient either suffering from Actos bladder cancer or at risk for same by continuing with Actos, is what now? Where do they turn?

And will the loss of the patent for Actos, and the introduction of less-expensive generic formulations of pioglitazone, introduce the increased risk associated with Actos bladder cancer to an even larger segment of the population?

According to the FDA, the best they can do is, well, maybe.

In the meantime, stay tuned. And be prepared to get out of the way of the next Actos bladder cancer lawsuit to come along. There are plenty of them, and traffic is heavy.