PURPOSE: Imiquimod, a TLR-7 agonist, is effective as topical treatment for skin malignancies.
TMX-101 is a liquid formulation of imiquimod. The objective of this study was to establish a safety profile of TMX-101 in patients with non-muscle invasive bladder cancer (NMIBC).
MATERIAL AND METHODS: We conducted a multicentre phase-I dose-escalation study in NMIBC patients. Patients were included in one of four dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with six weekly instillations TMX-101, starting two weeks after TURBT. Patients were evaluated weekly and pharmacokinetic and -dynamic parameters were measured.
RESULTS: Sixteen patients were included, four per dose-group. Two patients dropped out after the second instillation in dose-group one and two. In total, 88 instillations were administered without serious adverse events. There were 118 adverse events (AE's), of which 84 were related to the study drug. All AE's were mild or moderate and number or severity were not correlated with dose-group. Of the related AE's, 70% was confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose-group 3 (0.2%, 100 mg). Maximum plasma concentration in dose-group 4 (0.4%, 200 mg) was 71.7 ng/mL. This is below plasma concentrations of 123 and 128 ng/mL without significant side effects measured in healthy volunteers after subcutaneous (30mg) or oral intake (100mg) of imiquimod, respectively.
CONCLUSIONS: Intravesical treatment with TMX-101 is safe: side-effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.
Written by:
Falke J, Lammers RJ, Arentsen HC, Ravic M, Pozzi R, Cornel EB, Vergunst H, de Reijke TM, Witjes JA. Are you the author?
Radboud University Nijmegen Medical Centre, Department of Urology, Nijmegen, The Netherlands.
Reference: J Urol. 2012 Nov 30. pii: S0022-5347(12)05771-0.
doi: 10.1016/j.juro.2012.11.150
PubMed Abstract
PMID: 23206424
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