Assessment of the efficacy of repeated instillations of mitomycin C mixed with a thermosensitive hydrogel in an orthotopic rat bladder cancer model. Issue 7 (July 2018)

• Record Type: Journal Article
• Authors: van Valenberg, F. Johannes P.; Strauss-Ayali, Dalit; Agmon-Gerstein, Yael; Friedman, Astar; Arentsen, Harm C.; Schaafsma, H. Ewout; Witjes, J. Alfred; Oosterwijk, Egbert
• Is Part Of: Therapeutic advances in urology. Volume 10:Issue 7(2018)
• Page Start: 213
• Page End: 221
• Publication Date: 2018-07
• Subjects: animal models -- bladder cancer -- mitomycin C -- thermosensitive hydrogel -- urinary bladder neoplasms; Urology -- Periodicals; Urologic Diseases -- therapy -- Periodicals; Genital Diseases, Male -- therapy -- Periodicals; Urologie -- Périodiques; 616.6005
• DOI: 10.1177/1756287218762064
• Languages: English
• ISSNs: 1756-2872

Abstract

Background: We investigated a thermoreversible hydrogel that is highly viscous at body temperature, while fluid-like at a low temperature, thus aiming for a slow and prolonged intravesical drug release. Our study purposed to assess antitumor efficacy of mitomycin C (MMC) mixed with hydrogel in an orthotopic rat bladder cancer model. Methods: Bladders of female Fischer F344 rats were grafted with 1.5 × 10 6 AY-27 urothelial carcinoma cells. On day 5, tumor presence was assessed by cystoscopy and rats were divided into six groups (five treatment, one control, n = 10/group). Intravesical treatments (0.5 mg or 1 mg MMC-H2 O or MMC-hydrogel, or 2 mg MMC-hydrogel) were administered on days 5, 8 and 11. Rats were sacrificed at day 14 and bladders were evaluated. Results: Rats with tumor at cystoscopy (47/60) were evaluated for efficacy. At necropsy, all control animals (8/8) had tumors. No microscopic tumors were present in the 0.5 mg and 1 mg MMC-hydrogel groups compared with 2/8 and 1/8 rats in the 0.5 mg and 1 mg MMC-H2 O groups ( p = 0.47 and p = 1.00, respectively). Greater toxicity was seen in animals treated with MMC-hydrogel compared with MMC-H2 O, as demonstrated by lower body weights at necropsy ( p = 0.000) and a tendency for more severe clinical signs in the 1 and 2 mg MMC-hydrogel groups. Rats that died prematurely received 1 mg (4/10) or 2 mg (9/10) of MMC-hydrogel. Conclusions: Under the current model conditions it is unclear whether instillation of MMC-hydrogel is more effective than MMC-H2 O. Nonetheless, the observed difference in toxicity, acting as a surrogate marker for systemic MMC exposure in the MMC-hydrogel-treated rats, supports the prolonged drug release mechanism of the hydrogel.