Actos & Bladder Cancer

In light of mounting concern over Actos and bladder cancer, the U.S. Food and Drug Administration (FDA) has ramped up its review of the popular type 2 diabetes medication. First introduced by Takeda Pharmaceuticals in 1999, Actos (pioglitazone) has been the subject of increasing scrutiny over potentially life-threatening side effects, including a causal link to bladder cancer and heart failure – so much that in 2002, the FDA ordered a 10-year epidemiological study of the drug and its inherent risks. In June 2011, the federal agency issued a safety communication regarding its findings of a 40% increased risk of bladder cancer among patients who took Actos at high doses for one year or longer.

Before Actos was released on the market, early clinical trials revealed an association between pioglitazone and bladder cancer. Nevertheless, health care providers and patients were uninformed about potential bladder cancer risks, and sales of the diabetes drug skyrocketed. Over the years, medical studies conducted both in the U.S. and abroad have shown that these risks may be much greater than originally thought. New research published in the British Medical Journal suggests that individuals who take Actos may actually have an 83 percent increased chance of developing cancer.

Studies reveal Actos and bladder cancer link

Research published in the May 2012 edition of the British Medical Journal revealed the surprisingly high risk of bladder cancer among Actos users. The study analyzed data regarding more than 115,000 patients who were treated with diabetes medications from 1988 to 2009. The researchers discovered an 83 percent increased bladder cancer risk among those who took pioglitazone. Lead researcher Laurent Azoulay PhD. concluded, “Patients with type 2 diabetes and their physicians need to be fully aware of the potential association between Actos and bladder cancer.”

The American Diabetes Association (ADA) published a report in March 2011, which reviewed FDA adverse drug reports concerning Actos and bladder cancer. The report concluded that “preliminary data found an increasing risk of bladder cancer with pioglitazone exposure, with statistical significance after 24 months.”

One of the most notable studies cited in Actos lawsuits is the 10-year epidemiological trial conducted by Kaiser Permanente and overseen by the FDA. The extensive research was mandated in 2002 after early Actos studies in rats showed an increase in bladder tumors. The final results are slated to be published in late 2013, but a review of the five-year interim data prompted the FDA’s 2011 pioglitazone label update alerting consumers about the heightened risks of bladder cancer in Actos users.

On June 9, 2011, the French Medicines Agency decided to suspend the use of Actos after its three-year PRO-active study showed a statistically significant increase in the risk of bladder cancer in men exposed to the drug for more than a year. The study included 1.5 million patients and was conducted from 2006 to 2009. On June 10, 2011, Germany joined France in suspending the sale of Actos, and urged doctors not to prescribe the medication to any new patients. The type 2 diabetes medication remains on U.S. shelves.

How does Actos cause bladder cancer?

According to research from the National Cancer Institute, individuals with type 2 diabetes are already at a higher risk for developing bladder cancer. Actos belongs to a class of drugs called thiazolidinediones (TZD), which are used to help regulate blood sugar levels in diabetics because they make the body more sensitive to insulin. Cancer cells have insulin receptors, meaning they can use insulin to grow. Because Actos functions by reducing the amount of available insulin, the association between Actos and bladder cancer may be a direct effect of the way the medication works. Though scientists are unsure as to how pioglitazone provokes the development of cancerous cells within the bladder, numerous medical studies have demonstrated an elevated risk of bladder cancer among patients who ingest high doses of Actos for prolonged periods of 12 months or longer.

Risk factors for bladder cancer

In their 2011 safety announcement, the FDA warned the public that individuals who take pioglitazone for longer than a year have a 40 percent increased risk of developing bladder cancer as compared to patients who did not use the medication. This warning was based on the five-year interim analysis of 193,099 diabetic patients who were treated with Actos for an average of two years. The FDA concluded that patients with the longest exposure to and the highest cumulative dose of the medication were at greater risk.

The following are other risk factors for bladder cancer:

• Smoker
• Male
• Caucasian
• Exposure to toxic chemicals used in dyes, rubber, leather, textiles and paints
• Previous cancer treatment
• Chronic bladder inflammation
• Family history of cancer

Symptoms of bladder cancer

While the majority of warning signs are subtle, early symptoms of bladder cancer may include:

• Blood in urine (hematuria)
• Painful urination
• Pelvic pain
• Lower back pain
• Unexplained weight loss
• Reoccurring bladder infections
• Frequent urination

Diagnosis of bladder cancer

A bladder cancer diagnosis in the early stage of the disease is highly treatable. However, reoccurrence is common among patients with bladder cancer, even in its early stages. The good news is that the five-year survival rate is almost 80 percent.

Common tests used to diagnose bladder cancer include:

• Cystoscopy to examine the urethra and bladder, generally performed under local anesthetic
• Biopsy to collect a cell sample for testing
• Urine cytology to look for cancer cells
• Imaging tests such as a CT scan or intravenous pyelogram to examine the kidneys, ureter and bladder

Treatment for bladder cancer

Bladder cancer treatment options depend on the type and stage of the disease and a patient’s overall heath.

Stage 0 through 1 treatments

• Transurethral Resection – cauterizes the cancerous cells
• Segmental cystectomy – removes a portion of the affected bladder
• Chemotherapy and immunotherapy (biological therapy) – to shrink the tumor and slow down the early-stage disease

Stage II, III and IV treatments (muscle invasive)

• Radical cystectomy – surgery removes the diseased bladder and replaces it with one of several urinary diversions
• Chemotherapy and immunotherapy – kills the cancer cells and stops the disease from spreading further
• Clinical trials – with new medicines and innovative therapies

Why patients are filing Actos lawsuits

With concrete evidence and FDA-sponsored studies demonstrating a link between Actos and an significantly increased risk of bladder cancer, injured patients have taken to suing Takeda for the manufacturer’s failure to warn of the drug’s potential dangers. Some legal experts speculate that the pharmaceutical giant could soon face more than 10,000 Actos lawsuits, based on charges of gross negligence, fraudulent concealment, failure to warn and strict liability. Since the 2011 FDA warning concerning pioglitazone and increased bladder cancer risks, more diabetes patients who took the medication are coming forward claiming Actos is the direct cause of their disease. Those affected should consult with a qualified Actos lawyer, experienced in pharmaceutical litigation.

The U.S. Judicial Panel on Multidistrict Litigation (JPML) centralized all federal Actos bladder cancer lawsuits in the U.S. District Court for the Western District of Louisiana, and state-level complaints were consolidated in Los Angeles, California. According to the claims against Takeda, had additional pre-market studies been conducted, the company could have detected these side effects much sooner, and prevented many patients from developing bladder cancer. Claimants also allege that Takeda knew of bladder cancer risks as early as 1999 in animal trials, but failed to warn consumers and the medical community.