(UroToday.com) In a podium presentation in the Late-Breaking Abstracts session at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Taylor presented interim results of a trial of intravenous (IV) vitamin C in combination with chemotherapy in patients with muscle-invasive bladder cancer who are ineligible for cisplatin.
Among patients with muscle-invasive bladder cancer (MIBC) or locally advanced disease, neoadjuvant cisplatin-based chemotherapy (NAC) prior to radical cystectomy is considered the standard of care. However, approximately 40% of patients will be cisplatin-ineligible due to renal insufficiency, hearing loss or poor performance status. Alternative chemotherapy regimens including gemcitabine and carboplatin (GCa) have limited success in this setting and, as a result, the standard of care is upfront cystectomy without realizing the potential survival benefit afforded by NAC. Vitamin C can preferentially lead to cellular death in cancer cells compared to normal cells in a process mediated through reactive oxygen species.
In other disease settings and models, intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve the efficacy of carboplatin and gemcitabine-based therapy. The authors, therefore, designed this single-arm, Simon 2-stage, window of opportunity trial including IV vitamin C with single-cycle GCa to evaluate pathologic downstaging among patients undergoing radical cystectomy. In this presentation, Dr. Taylor provided results from the interim first stage analysis of 12 patients.
The authors enrolled cisplatin-ineligible patients who were newly diagnosed with MIBC. Patients received a single cycle of GCa and IV vitamin C titrated to a peak plasma concentration of 350 to 400 mg/dL (∼20 mM) for 21 days followed by cystectomy at 4-6 weeks from initiation of treatment. Notably, while most inclusion and exclusion criteria were in keeping with what would be expected in this disease space, patients consuming tobacco products as well as those with a history of G6PD deficiency were excluded on the basis of concerns regarding the ability to get sufficient Vitamin C levels intravenously.
The primary outcome of interest was pathological stage at cystectomy. Following cystectomy, patients were followed according to NCCN guidelines with the standard of care bloodwork, physical exam and imaging studies until progression and/or death. Patient-reported quality of life (QOL) was evaluated using the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) measure.
In this preliminary analysis, 12 included patients among 16 who have been consented completed GCa with IV vitamin C with 11 having undergone cystectomy to date with 1 pending surgery.
Overall, treatment was well tolerated with no treatment-related adverse events.
Among the 11 evaluable patients, pathological downstaging (yp <T2) was seen in 4 patients with 3 of these patients having CRs (ypT0N0Mx) and the remaining having residual ypTisN0Mx disease. One of the three patients with a CR had locally advanced disease with a plasmacytoid variant, a phenotype typically associated with poor prognosis. The authors further noted that treatment was well tolerated with minimal treatment related AE/SAEs.
Thus, Dr. Taylor concluded that this interim analysis of a trial of GCa with IV vitamin C prior to radical cystectomy shows good tolerability with a promising 36% rate of downstaging. As a result of these favourable results, the continuation criteria has been met for stage 2 of this trial. FACT-BI analysis and clinical follow up is ongoing and will be reported at study completion.
Presented by: John Arthur Taylor, III, MD, MS, John W. Weigel Professor of Urology & Cancer Biology, University of Kansas Medical Center
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.