The unfortunate reality is that kidney problems often result from bladder cancer which precludes the usual chemotherapy package of cisplatin and gemcitabine, says Dr. Teresa A. Coleman, hematologist-oncologist at the MCG Cancer Center.
A Phase II study at about 120 sites in North America, Europe and Asia will determine if those patients can benefit from vinflunine, which is in the same vinca alkaloid family as Navelbineģ, used for lung cancer.
These vinca alkaloids keep cells from dividing properly so the tumor can't grow and existing tumor regresses, says Dr. Coleman, a principal investigator on the study sponsored by Bristol-Myers Squibb.
Patients with stage two disease, which has spread beyond its origin in the bladder's lining, typically get cisplatin and gemcitabine before or after surgery or in conjunction with radiation therapy. However, a major side effect of cisplatin is kidney failure, and gemcitabine alone is believed not to be nearly as effective. "The most effective drug we have can't be used in some patients," Dr. Coleman says.
Bladder cancer, the sixth most common cancer, often obstructs tubules that connect the kidney to the bladder, says Dr. Coleman. While the cancer typically doesn't spread upward, tubule blockage damages the kidneys. Additionally, bladder cancer incidence peaks in the 60s and 70s when other diseases, such as type 2 diabetes and uncontrolled blood pressure, may also have damaged the kidneys, she says. These scenarios make more than 50 percent of patients age 70 to 80 and an estimated 30 percent of all bladder cancer patients are ineligible for cisplatin.
"I see so many patients who come to my office with kidney damage for a variety of reasons, and I have little for them really," says Dr. Coleman. A chemotherapy regimen that includes the drug carboplatin instead of cisplatin - both platinum-based compounds that also keep cancer cells from dividing - is more kidney friendly but less effective than the cisplatin regimen, studies have shown. Bristol-Myers Squibb produces cisplatin and carboplatin.
Participants will either get vinflunine and gemcitabine or gemcitabine alone. They will get the drug regimen intravenously on days one and eight of a 21-day cycle. Patients who do well may continue taking it up to a year or more.
Anemia is the major side effect of vinflunine, which suppresses the bone marrow, but existing anemia does not exclude patients from the trial, Dr. Coleman says.
She hopes the regimen will be at least as effective as the cisplatin therapy, which gives patients with non-metastatic disease about a 50-50 chance of living five years. An earlier study in patients with advanced cancer who received a previous chemotherapy regimen, then vinflunine alone, showed 67 percent had their disease stabilized.
Smoking is the number-one risk factor for bladder cancer. The first symptom is often blood in the urine. "Bladder cancer begins in the urinary lining of the bladder," says Dr. Coleman. "When that lining is disrupted, it's like pulling layers of skin off. You will bleed into your urine. You can have pain, but that's usually a later sign."
Physicians will examine the lining and take a biopsy to determine the extent of the cancer. "If you catch it early, it's absolutely curable," Dr. Coleman says. Physicians literally tear off the diseased lining, which will eventually re-grow. If it's the early stage- one disease, but an aggressive form, BCG, an agent used as a vaccine for tuberculosis that stimulates an immune response, is injected directly into the bladder once a week for six weeks.
The fact that the bladder is literally a sac makes it a target for cancer by holding liquid toxic waste from a smoker's body, Dr. Coleman says. However, it also means that some patients can get localized treatment for their disease.