Orlando, FL--Gemcitabine (Gemzar) administered as an intravesical instillation appears to be well tolerated and to demonstrate modest efficacy in patients with stage Ta, grade I/II urinary bladder cancer, with about one-third of patients achieving a response. However, a twice-weekly dose given for 3 weeks is comparable in efficacy to a once-weekly dose given for 6 weeks, a new study suggests, and a single dose given once is not effective in this patient population.
Researchers at five hospitals in Sweden, coordinated from the Uppsala University Hospital, evaluated the efficacy and toxicity of three different dose regimens of gemcitabine administered intravesically to 32 patients with histologically proven stage Ta, grade I/II urinary bladder cancer and a marker lesion diameter of 0.5 to 1 cm after transurethral resection.
All subjects received instillations of gemcitabine, 2,000 mg, left in the bladder for 1 hour. Patients were randomized to one of the following regimens: one dose, two doses per week for 3 weeks, or one dose per week for 6 weeks. Cystoscopy was used to assess response 9 weeks after treatment was completed.
No grade 3/4 toxicities (based on National Cancer Institute Common Toxicity Criteria) were observed among the 30 patients evaluable for toxicity. Grade 1/2 nausea was reported in five patients (17%), and grade 1/2 fever was observed in two patients (7%). One patient had grade 1 reversible thrombocytopenia, and one patient with fever had reversible grade 1 anemia.
Treatment was stopped as a result of toxicity in one patient. Ten patients (33%) were unable to retain the drug for the full hour.
Alternative to BCG?
"This was a small study, but from what has been presented so far in smaller phase II studies, a complete response rate of between 42% and 67% may be expected," Dr. Gårdmark told Urology Times at the American Society of Clinical Oncology annual meeting. "Furthermore, if the side effects are as mild as has been indicated, [intravesical gemcitabine] may become an alternative to current therapies."
"The need for intravesical chemotherapy in the treatment and prevention of superficial bladder cancer has been long recognized," noted Nicholas Vogelzang, MD, director of the Nevada Cancer Institute in Las Vegas. "These patients do not have systemic disease, and thus do not need systemic chemotherapy.
"However, they are prone to repeated relapses of the low-grade cancers within the bladder. Usually, such cancer can be treated with resection, but in some cases, resection via the cystoscope cannot be accomplished. In such cases, intravesical therapy with a drug is used."
According to Dr. Vogelzang, the Swedish group's study confirms the activity of gemcitabine, reported by Dalbagni and colleagues (J Clin Oncol 2002; 20:3193-8).
"Whether gemcitabine will be better than BCG in preventing relapse of superficial cancers remains unclear," he said.