Intravesical Chemotherapy Recommendations, 2005

Despite BCG being repeated demonstrated to be superior to intravesical chemotherapy, chemotherapy still plays an important role in the optimal management of superficial bladder cancer. Here are my current recommendations for the optimal use of intravesical Thiotepa, Mitomycin C, and Doxorubicin.

Immediate Postoperative Instillation is now confirmed by individual controlled trials and meta-analysis to be highly effective in reducing tumor recurrence, even in solitary, low grade TCC. A single instillation within 6 hours of tumor resection markedly reduces recurrence, presumably by preventing seeding as well as destroying remaining cancer cells. Recurrence is still high in patients with multiple tumors, in which case 3-5 additional treatments may be beneficial. Immediately post TURBT I use Thiotepa 30mg in 15cc water for 30" because it has the best penetration and is not caustic. Unlike Mitomcyin C and Doxorubicin, Thiotepa can be given intraperitoneally and is safe even if there is a bladder perforation, and even if it is 100% absorbed (IV dose 0.5mg/KG). If you are certain that there is no perforation, MMC 40mg/20cc or Adria 50mg/25cc can be used.

Chemotherapy Principles are important and too often ignored. Tumor kill is proportional to concentration (not dose) and duration of exposure with topical chemotherapy. Controlled studies have demonstrated significant improvement when concentration and pH are optimized. Adria is particularly useful in MMC and TTP failures because it is an intercalating agent and they are alkylating agents.

To maximize concentration and provide optimal pH, patients are instructed to restrict liquids after midnight. 2 Alka Seltzer tablets or 1.2gm bicarbonate are taken hs, am, and just before the procedure to alkalanize the urine (MMC is inactivated by acid urine and cytotoxicity of TTP and Adria is better in alkaline pH). Extra care, even using ultrasound if needed, is taken to completely empty the bladder before instillation. Patients are placed on their abdomen for 15" and asked to retain the solution for 2 hours.

Drug doses: Thiotepa 30mg/15cc (or 60mg/30cc); Mitomycin 40mg/20cc; Doxorubicin 50mg/25cc. All drugs are diluted, when needed, with water. Repeated administration of Thiotepa should not be done without confirming that blood counts are normal. Myelosuppression can also occur with Mitomycin, but does not occur with Doxorubicin.

New Treatments being evaluated include electromotive administration and hyperthermia, and both appear to improve efficacy. Epirubicin (50mg/25cc), an anthracycline similar to doxorubicin, is popular in Europe. Gemcitabine (1,000mg/50cc) is highly effective systemically and encouraging in early studies.

Created: 3/15/2005