Ask the Doctor

Fall 2007

Our questions for this issue of Outlook were answered by Donald Lamm, M.D. of BCG Oncology in Phoenix, AZ. We sincerely appreciate his sharing his opinions and impressions with us.

Q. BCG was approved for the treatment of bladder cancer in 1990, and remains the primary intervesical treatment for bladder cancer. Are there new agents on the horizon which may work as well—or even better—than BCG?

A. The success of BCG has been a great help to many patients, but no treatment works for everyone. Even with the optimal BCG treatment schedule, about 20% of patients will fail to respond. With time, many patients who respond will initially fail BCG. Other patients have side effects that prevent them from receiving BCG. All of these add up to as much as 50% of bladder tumor patients who need a treatment other than BCG. That’s why new alternative treatments for non muscle-invasive bladder cancer are needed. Unfortunately, when drugs are to be submitted for study to the FDA, they are generally compared with BCG. And because BCG is so effective it is difficult to find something better. In addition, to prove a new treatment is better requires hundreds if not thousands of patients. This becomes financially prohibitive for many companies. Nonetheless, there are some encouraging drugs being developed. Here is a small sampling:

•Improved Mitomycin Treatment. While Mitomycin (MMC) is found to be less effective than BCG in many studies, including our Southwest Oncology comparison, significant improvements in MMC are being developed. First and immediately applicable is the optimized MMC schedule: overnight dehydration, alkalinization of the urine, careful, confirmed bladder drainage and concentrated MMC at a dose of 40mg/20ml as described by Dr. Au. This schedule nearly doubles the efficacy of MMC. The second approach is to increase the penetration of MMC into the bladder wall, and this can be done using hyperthermia, electromotive techniques or by the addition of enzymes to increase penetration. All of these techniques are in trials and have the potential of significantly improving the response we see with MMC and other chemotherapies.

•New Chemotherapies. Eoquin, a drug related to Mitomycin C, is currently undergoing Phase 3 studies in the U.S. It is reported to be more potent than MMC. Gemcitabine and docetaxel or paclitaxel, drugs known to have efficacy in advanced bladder cancer, are being evaluated as intravesical agents. For patients who fail BCG, these drugs, or more recently drugs in used combination, offer a useful alternative.

•New Immunotherapies. Though not new, Keyhole Limpet Hemocyannin, the oxygen-carrying molecule from a South Pacific “sea snail” is known to be effective in bladder cancer and is approved for treatment in several countries. I have had patients respond who have failed all my other options, but unfortunately it is not approved in the U.S. MCC is a promising immune stimulant conceived by Dr. Morales, who first gave BCG to bladder cancer patients. Made by Bioniche, it is the cell wall of a bacterium related to BCG that does not cause disease (Mycobacterium Phlei). It acts by both stimulating the immune system as well as directly killing bladder cancer cells and is being evaluated in clinical trials in the US and Canada. Like combination chemotherapy, combination immunotherapy using BCG with Interferon, interleukin 2 or other immune molecules is also very promising.

•Gene Therapy. I know of three gene or DNA based treatments that are promising for bladder cancer. Investigators at MD Anderson have developed a gene treatment related to interferon production. In Israel, investigators have developed a DNA based treatment that targets H19, a molecule that can promote cancer progression. Clinical trials have demonstrated some success and further studies are planned. Another gene therapy trial underway in this country uses a virus that targets and kills cancer cells and also is thought to act as a vaccine. These exciting projects will take time to perfect and gain approval, but are promising for the future of bladder cancer treatment.

Q. Many patients who have had their bladders removed find themselves with frequent urinary tract infections. Is there anything a patient can do to prevent these infections? Will cranberry juice or any type of vitamin help in keeping such infections at bay?

A. We are learning that old wives can be very wise and cranberry juice does in fact have some antibacterial activity. It is important for patients with recurrent infection to take in an adequate amount of liquid (to wash out bacteria) and to avoid urine retention. With the ileal loop diversion, contamination with bacteria is expected, but with an open, low pressure system serious infection is generally avoided. The stoma can scar and become tight, restricting the flow of urine. This narrowing can often be avoided by simply dilating the stoma with a finger periodically. Those with neobladders need to try to keep residual urine to a minimum. “Double voiding” to get the last bit of urine out, or taking extra time to be sure the catheter drains all of the urine in an Indiana pouch, can reduce the number of infections. Sometimes it is necessary to take suppressive antibiotics. Alternatively, some patients do best when they have antibiotic on hand to take at the first sign of infection. We have not, to my knowledge, demonstrated that vitamins can reduce urine infections, but vitamin C has been used to acidify the urine and make it less hospitable to some bacteria.