Objective: A phase I/II study was initiated in patients with refractory localized superficial bladder cancer to establish the tolerance and toxicity of recombinant tumor necrosis factor (rTNF) given intravesically. A preliminary evaluation of patient responses to therapy was noted; however, the small trial size precluded extensive statistical assessment of the data.
Setting: A large teaching hospital, where patients were referred for treatment of recurrent superficial bladder cancer.
Patients: A referred sample consisting of 16 patients with a primary diagnosis of histologically documented superficial bladder cancer (stage Ta, T1, TIS), refractory to at least 1 previous therapy, were entered on the study. Eligibility criteria Included: 1) cystoscopy in last 42 days, 2) no contraindications to chemotherapy, 3) life expectancy of 3 months, and 4) informed consent.
Intervention: Patients were given rTNF intravesically twice weekly for 4 weeks at doses ranging from 10 to 500 mcg/m2.
Main outcome measures: Adverse effects were recorded as minimal, moderate, severe, or intolerable. Patient responses were measured on the basis of clinical and laboratory signs, symptoms, and tumor size.
Results: We observed no severe or intolerable toxicities associated with the treatment. Two patients had complete responses, 9 had partial responses, 2 had minor responses, 1 was diagnosed with progressive disease, and 2 were not evaluated. No maximum tolerated dose was determined because rTNF was well tolerated at a maximum dose of 500 mcg/m2.
Conclusions: The study drug rTNF was well tolerated up to a dose of 500 mcg/m2 and exhibited some antitumor effects against transitional cell carcinoma, but a biologically active dose was not determined. On the basis of this trial, further studies of intravesical treatment of superficial bladder cancer with rTNF appear warranted.