Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer.

摘要: Transforming growth factor alpha-Pseudomonas exotoxin-40 (TP40) is a hybrid fusion protein that selectively binds to cancer cells express the epidermal receptor. TP40 then internalized and kills these by virtue of its Pseudomonas exotoxin-derived domains. We studied safety short-term antitumor activity intravesical in 43 patients with refractory superficial bladder cancer. These had resected Ta/T1 disease (n = 19), visible Ta or T1 lesions 11), carcinoma situ 13). Patients were treated increasing dose levels at 0.15, 0.3, 0.6, 1.2, 2.4, 4.8, 9.6 mg/week for 6 weeks evaluated comparing pretreatment posttreatment cystoscopic examinations, cytology, histopathology. All doses well tolerated. No evidence was seen any lesions. However, 8 9 evaluable judged histopathology multiple biopsy specimens exhibit clinical improvement following therapy. In most responsive patients, examination supported histopathological findings, although cytology urine washings persistently demonstrated malignant cells. Therefore, appears be well-tolerated biological agent may prove have utility treating bladder.