Intravesical RTNF therapy of superficial bladder cancer. A phase I study of recombinant tumor necrosis factor administered intravesically to patients with superficial bladder cancer.

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.