Continuous intra-arterial administration of recombinant interleukin-2 in low-stage bladder cancer. A phase IB study

Abstract

Toxicity and clinical effects of intra-arterial (IA) continuous infusion of recombinant interleukin-2 (rIL-2) were evaluated in twelve patients with low-stage transitional cell carcinoma (TCC) of the bladder (T1NOMO; G1 to G2). rIL-2 dosages were escalated from 18 x 10(3) to 18 x 10(6) IU/m2/d in four groups of three patients. After two 5-day courses, separated by a 48-hour interval, evaluation of clinical response and transurethral resection (TUR) were carried out. World Health Organization (WHO) Grade 3 toxicity occurred in 2 of 12 patients (hypotension/mental confusion and fever, respectively); all side effects rapidly disappeared after infusion was abandoned. No laboratory toxicity developed in any patient. Two pathologically proven complete responses (CR) were achieved using 18 x 10(4) IU/m2/d, and three partial responses (PR) were achieved using 18 x 10(5) IU/m2/d in two patients and 18 x 10(6) IU/m2/d in one patient, giving an overall response rate of 42%. All objective responses are still ongoing after a mean follow-up time of 23 months (range, 12 to 32 months). Local relapses occurred 3 months after TUR only in two nonresponders.

Bladder Cancer Immunotherapy: BCG and Beyond

“…Multiple murine studies have demonstrated that systemic administration of IL-2, with or without BCG, can significantly decrease tumor size, suppress tumor growth, and improve mean survival [71–73]. A small clinical study investigating systemic IL-2 administration effects on low-stage bladder cancer found a complete and partial response rate in 5 of 12 patients, though 2 patients discontinued therapy due to toxicity [74]. The poor side effect profile of systemic IL-2 administration subsequently prompted a shift to utilize IL-2 as an intravesical therapy.…”

Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary bladder

“…Although the role of such mechanisms in the rejection of IL-2 gene-transduced bladder cancer cells has not been explored in the present study, an even more interesting support to their potential relevance in this tumour model comes from our earlier experience with intraarterial or intravesical rIL-2 treatment in patients with superficial transitional cell carcinoma of the bladder (Tubaro et al, 1991(Tubaro et al, , 1995Velotti et al, 1991aVelotti et al, , 1991b. In these clinical trials we observed a significant increase in the inflammatory response at the tumour site, with evident infiltration of tumour stroma and neoplastic epithelium by activated (CD25 + /HLA-DR + ) T-cells, macrophages and both eosinophil and PMN.…”