Actos: Symptoms of Bladder Cancer & Treatment

In June of 2011, the U.S. Food and Drug Administration issued a public safety alert about Actos and bladder cancer, stating that “use of the diabetes medication Actos (pioglitazone) for more than one year may be associated with an increased risk of bladder cancer.” The FDA based its warning on a 10-year study showing that people taking the drug for 12 or more months were at a 40% greater risk of developing bladder cancer than patients taking alternative type 2 diabetes drugs.

Because of the bladder cancer risk, Actos, which is manufactured by Takeda Pharmaceuticals, was pulled from the shelves in France and Germany in 2011. Despite the growing number of lawsuits filed by cancer patients who accuse Takeda of failing to adequately warn them about the risks they were facing by taking Actos, the drug reportedly generated $4.8 billion in revenue for the Japan-based company in 2012.

Bladder cancer is a form of cancer that usually originates in the bladder’s interior lining. The bladder is a balloon-shaped pelvic organ that stores urine. Though typically diagnosed in older adults, bladder cancer can express at any age. Bladder cancer is considered highly treatable if caught early, though even after successful remission there is a high probability of recurrence. For this reason, patients who have been successfully treated for bladder cancer typically return for frequent follow-up tests.

Actos is an oral medication that helps diabetics control their blood sugar levels. Actos is prescribed to patients who have been diagnosed with type 2 diabetes, and is sometimes used in combination with insulin.

Signs and symptoms of bladder cancer

Numerous studies in and out of the U.S. have established a link between Actos and bladder cancer. However, bladder cancer has been attributed to many other causes as well, including smoking (smokers are twice as likely as non-smokers to develop bladder cancer), radiation, parasitic infection, exposure to environmental chemicals, and changes in DNA. Men are four times more likely to develop bladder cancer than women, and white men are twice as likely to get it as African-American men. Diets high in nitrates, meat, and fatty foods have also been associated with an increased chance of developing bladder cancer.

Blood in the urine (also known as hematuria) is the most common sign of bladder cancer. Nearly 90% of bladder cancer patients report blood in the urine as a symptom. Urine may take on a reddish color, but may also appear dark yellow or cola-colored. In some cases, urine appears normal, and the microscopic amounts of blood can only be detected in lab tests.

Other common signs and symptoms of bladder cancer include:

• Frequent urination, or urinating small amounts frequently
• Painful urination
• Need to urinate without being able to do so
• Frequent urinary tract infections

Symptoms that may indicate a more advanced stage of bladder cancer include:

• Lower back pain (near the kidneys)
• Lower leg swelling
• Pelvic pain
• Pain in the rectum or anus
• Pelvic mass (growth in the pelvis)
• Anemia
• Weight loss

The symptoms of bladder cancer are similar to the symptoms of other non-cancerous disorders, including prostate infections, cystitis, ureteric stones, kidney disease, and vascular malformations. Patients who believe they exhibit any of the signs of bladder cancer are urged to consult a physician immediately.

Bladder cancer diagnosis

Patients exhibiting the signs and symptoms of bladder cancer are usually referred to a urologist, a doctor who specializes in diseases of the urinary tract and male reproductive organs. In addition to asking about a patient’s medical history—smoker? family history of cancer? work-related exposure to toxic chemicals?—a doctor will conduct a physical exam, which may include a rectal exam, a prostate exam for male patients, and a pelvic exam for women. A urine test may also be ordered to detect the presence of blood, infection, or abnormal cells.

In some cases, a doctor will perform a cystoscopy, in which a thin, lighted instrument is inserted into the urethra and slowly advanced into the interior of the bladder. Small surgical instruments may be inserted through the tube to take tissue samples for biopsy. This procedure is usually performed with a local anesthetic.

A variety of imaging tests may also be utilized to examine the urinary tract. Special dyes may be injected before the tests are conducted. An intravenous pyelogram is an X-ray that focuses on the kidneys and bladder. A computerized tomography (CT) scan is another X-ray, which focuses on the urinary tract and adjacent tissue.

Types of bladder cancer:

• Transitional cell carcinoma: Occurs in the cells that line the inside of the bladder. Transitional cells expand when your bladder is full and contract when the bladder is empty. These same cells line the inside of the ureters and urethra, and tumors can form in those places as well. Transitional cell carcinoma is the most common type of bladder cancer.
• Squamous cell carcinoma: Squamous cells appear in the bladder in response to infection and irritation. They can become cancerous over time. Squamous cell bladder cancer is most common in parts of the world where a certain parasitic infection (schistosomiasis) is a prevalent cause of bladder infections.
• Adenocarcinoma: Adenocarcinoma begins in cells that make up mucus-secreting glands in the bladder. Adenocarcinoma of the bladder is rare in the U.S.

If initial tests indicate a positive result for bladder cancer, a new battery of tests will be run to determine what stage and grade the cancer has reached. The stage is identified by the extent of the cancer’s growth into the bladder wall and its extension to nearby organs, including the liver and lungs. Grade is established by comparing the cancer cells to normal bladder cells. All of these factors are considered when evaluating a patients’s treatment options and prognosis.

Tests to determine stage and grade of the disease include:

• CT scan
• MRI (magnetic resonance imaging)
• Bone scan
• Chest x-ray
• CBC (complete blood count)

The 4 stages of bladder cancer are as follows:

• Stage 1: Cancer is present in the bladder’s inner lining, but has failed to reach the bladder wall.
• Stage 2: Cancer extends to the bladder wall, but not outside of the bladder.
• Stage 3: Cancer cells spread to surrounding tissue, including the prostate in men or the uterus or vagina in women.
• Stage 4: Cancer spreads to the lymph nodes and other organs, including liver, lungs, and bones.

Bladder cancer treatment

Over 90% of diagnosed patients elect to have surgery. Depending on the stage and grade, surgery may be performed to:

• Extract the tumor
• Extract the tumor and a small portion of the bladde
• Remove the entire bladder
• Create a new way to expel urine

Other bladder cancer treatment options include:

• Chemotherapy: Drugs that kill cancer cells are administered either intravenously, or directly to the bladder through a tube in the urethra. Side effects of chemotherapy include loss of appetite, vomiting, diarrhea, mouth sores, hair loss, and infection.
• Immunotherapy: Drugs are administered to stimulate the body’s immune system to fight the cancer cells.
• Radiation: High-energy beams are targeted to specific areas of the body to destroy cancer cells. It is often combined with surgery and/or chemotherapy.

Bladder cancer is often detected early, and is treated with a relatively high success rate. Because medical research has established a solid link between Actos and an increased risk of bladder cancer—a recent study from the UK suggests that patients taking pioglitazone for 5 or more years have a significantly greater chance of developing bladder cancer than other diabetics—people taking Actos for more than 12 months are advised to get tested regularly.