ABSTRACT
PURPOSE: To compare the effect of intravesical interleukin-2 (IL-2) instillations with and without a marker lesion on time to recurrence (TTR) in non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: A prospective randomized, controlled trial was conducted. Patients with multiple non-muscle-invasive tumours were randomized for a complete or incomplete transurethral resection (TURBT), followed by 3 IL-2 instillations. The primary end point was TTR. RESULTS: These are the results of an interim analysis, which was performed due to slow accrual after which the study was closed prematurely. Twenty-eight patients were randomized of which 17 were eligible on an intention-to-treat basis. Median TTR or last follow-up was 3 months (interquartile range [IQR] 3-10 months) for the complete and 4 months (IQR 3-8 months) for the incomplete TURBT group. The TTR between the 2 groups did not differ significantly (log-rank, p = 0.54). -Conclusions: These data do not support the hypothesis that a marker lesion enhances the therapeutic effect of IL-2 instillations in patients with NMIBC.
Subject(s)
Biomarkers, Tumor/metabolism , Interleukin-2/pharmacology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Administration, Intravesical , Aged , Cystoscopy , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/drug therapy , Netherlands , Prospective Studies , Quality of Life , Surveys and Questionnaires , Time Factors , Urinary Bladder Neoplasms/metabolismABSTRACT
In this study, the in vivo biocompatibility of physically crosslinked dextran hydrogels was investigated. These hydrogels were obtained by mixing aqueous solutions of dextran grafted with L-lactic acid oligomers and dextran grafted with D-lactic acid oligomers. Gelation occurs due to stereocomplex formation of the lactic acid oligomers of opposite chirality. Since gelation takes some time, in situ gel formation is possible with this system. A number of sterilization methods was evaluated for their effect on the chemical and physical properties of the hydrogel. It was shown that of the investigated options (filtration, gamma irradiation, dry-heat and autoclaving) dry-heat sterilization was the preferred method to prepare sterile gels suitable for in vivo evaluations. Two types of stereocomplex gels were prepared and implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 30 days. A mild ongoing foreign body reaction was observed characterized by infiltration of macrophages. Giant cells were only scarcely formed and the low numbers of lymphocytes showed that priming of the immune system is hardly involved. Importantly, the gels fully degraded in vivo within 15 days, which is in good agreement with the in vitro degradation behaviour of these gels. In conclusion, stereocomplexed dextran-oligolactic gels showed good biocompatibility which makes them suitable candidates for the design of controlled release devices for pharmaceutically active proteins.