Abstract
Abstract 2119: Intravenous vitamin C therapy for cisplatin ineligible bladder cancer patients (CI-MIBC): Early investigation into potential pharmacodynamic biomarkers
Cancer research (Chicago, Ill.), Vol.83(7_Supplement), pp.2119-2119
04/04/2023
DOI: 10.1158/1538-7445.AM2023-2119
Abstract
Abstract Neoadjuvant cisplatin based chemotherapy is considered standard of care for patients with locally advanced bladder cancer (BCa). However, upwards of 50% of patients are ineligible due to poor performance status, underlying kidney disease, peripheral neuropathy, hearing loss and/or cardiac disease. There are currently no accepted alternative regimens with significant activity, and many cisplatin ineligible patients usually proceed directly to surgery. Prior research in other cancers has indicated intravenous vitamin C (IVC), or ascorbate, may serve as a beneficial adjuvant to less toxic therapeutic regimens. We initiated a single arm, Simon 2-stage, Window of Opportunity trial using high dose IVC with single cycle gemcitabine/carboplatin (GCa) (NCT04046094). The primary outcome was pathologic downstaging. Twelve patients with newly diagnosed CI-MIBC were enrolled. Patients received single cycle GCa and IVC titrated to 350-400 mg/dL for ~21 days followed by cystectomy after ~4-6 weeks. As reported, pathological downstaging (<ypT2N0Mx) was present in 4 (33%) of patients. Three of the four patients had a complete response (ypT0NoMx) including one patient with plasmacytoid variant histology. Treatment was well tolerated with no attributable AE/SAEs. Given the discrepancy in response levels, we began identifying potential markers of pharmacodynamic efficacy to inform future trials. Novel data evaluating Ki67+ cells by immunohistochemistry indicate widespread proliferation in non-responders to IVC/GCa, whereas responding patients had visibly fewer positive cells, suggesting a direct effect on cell death and proliferation. TUNEL staining was present in all samples, although often minimally, and thus TUNEL may not yield enough signal to reliably make determinations about treatment outcomes. Urinary cytokine values were assessed using multiplex ELISA and reported as pg/mL urine. Multiple cytokines including IL-1RA, CCL2, IL-8, CXCL10 were present at markedly high concentrations in patients with BCa. Cytokine levels generally increased between diagnostic resection and radical cystectomy indicating potential immune activation by the IVC/GCa treatment. Cytokine levels generally fell between radical cystectomy and follow-up samples suggesting resolution of inflammation after cystectomy. In conclusion, IVC/GCa may be a viable alternative neoadjuvant treatment strategy for patients with BCa that are ineligible for cisplatin-based chemotherapy. Identifying biomarkers of response remains a major area of interest to refine study designs and identify patients most likely to benefit from therapy. Citation Format: Benjamin L. Woolbright, Ganeshkumar Rajendran, Erika Abbott, Zeb Zacharias, Jon Houtman, Rahul Parikh, Qi Chen, Ameer Hamza, Elizabeth Wulff-Burchfield, Jeffrey M. Holzbeierlein, Jeanne Drisko, Michael D. Henry, John A. Taylor. Intravenous vitamin C therapy for cisplatin ineligible bladder cancer patients (CI-MIBC): Early investigation into potential pharmacodynamic biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2119.
Details
- Title: Subtitle
- Abstract 2119: Intravenous vitamin C therapy for cisplatin ineligible bladder cancer patients (CI-MIBC): Early investigation into potential pharmacodynamic biomarkers
- Creators
- Benjamin L. Woolbright - University of Kansas Medical CenterGaneshkumar Rajendran - University of Kansas Medical CenterErika Abbott - University of Kansas Medical CenterZeb Zacharias - University of IowaJon Houtman - University of IowaRahul Parikh - University of Kansas Medical CenterQi Chen - University of Kansas Medical CenterAmeer Hamza - University of Kansas Medical CenterElizabeth Wulff-Burchfield - University of Kansas Medical CenterJeffrey M. Holzbeierlein - University of Kansas Medical CenterJeanne Drisko - University of Kansas Medical CenterMichael D. Henry - University of IowaJohn A. Taylor - University of Kansas Medical Center
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.83(7_Supplement), pp.2119-2119
- DOI
- 10.1158/1538-7445.AM2023-2119
- ISSN
- 1538-7445
- eISSN
- 1538-7445
- Language
- English
- Date published
- 04/04/2023
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Radiation Oncology
- Record Identifier
- 9984413073002771
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