G‐ <scp>DISCO</scp> : Gemcitabine‐Docetaxel Intravesical Synchronous <scp>CO</scp> ‐administration – a phase 1 study protocol

Gemcitabine-Docetaxel Intravesical Synchronous CO-administrationa phase 1 study protocolPatients with high-risk non-muscle-invasive bladder cancer (NMIBC) who are ineligible for or unresponsive to BCG therapy have limited treatment options.In patients who choose not to undergo radical cystectomy or are unsuitable for surgery, bladder-sparing approaches are needed.Combination intravesical chemotherapy using gemcitabine and docetaxel, administered sequentially, is increasingly used in this setting [1,2].However, this regimen is time-intensive for both patients and clinical services.The standard approach requires sequential instillations of each drug, typically necessitating up to 4 h of procedural time per session [3].To address this burden, we designed the G-DISCO (Gemcitabine-Docetaxel Intravesical Synchronous COadministration) study, a first-in-human phase I trial to assess the safety, feasibility and tolerability of administering these two agents synchronously via a single instillation.The rationale for this study lies in both patient convenience and health service efficiency.Gemcitabine and docetaxel are wellestablished intravesical agents, and retrospective studies have demonstrated the efficacy of sequential administration in BCG-unresponsive NMIBC, with reported 1-year recurrencefree survival rates of 49%-68% and 5-year bladder preservation rates of 75% [4,5].Whilst the use of intravesical gemcitabine and docetaxel is not novel, the proposed synchronous instillation of both cytotoxic agents is.