Continuous infusion 5-fluorouracil (5FU) as a novel treatment for heavily pretreated prostate cancer patients: An update.

Abstract

319 Background: Currently patients failing multiple conventional therapies enroll on clinical trials but in many cases, despite a good performance status, patients may not qualify for trial enrollment. CRPC tumor cells typically express prostate specific membrane antigen (PSMA), a folate hydrolase which increases cell folate uptake (Yao et al. Prostate 70:305, 2010). We hypothesize that 5FU, functioning as an anti-folate, antagonizes the downstream effects of PSMA over-expression. Herein we present an update to our 5FU experience in heavily pretreated mCRPC. Methods: Data was retrospectively collected at Tulane Cancer Center for patient treatment history, disease history, performance status and laboratory parameters. All patients were treated with continuous infusion of 5-fluorouracil at a dose of 200mg/m2-day. Results: 24 patients at Tulane Cancer Center were treated with 5FU between Oct/2013 and Oct/2018. The median age was 72, patients had an median of 6 lines of prior therapy, and 37.5% had liver metastatic disease. The 30% and 50% PSA response rates were 41.6% and 29% respectively. Of the PSA responders, 100% had some level of PSA decline after 7 days of therapy with a median time to best PSA response of 2.6 months (95% CI 0.2-5.1). Median time on treatment was 11 weeks for the entire cohort and 18.5 weeks for patients with a ≥30% PSA decline; 20.8% of patients remained progression free by PSA at 4 months. Improvement in performance status as well as transfusion independence were noted in a subset of patients with myelophthistic anemia due to prostate cancer. No grade > 3 AEs were attributable to 5FU. Conclusions: 5FU is a relatively inexpensive and well tolerated therapy that shows benefit in some heavily pretreated patients. Additionally, the ability to quickly assess the potential for response, and lack of > grade 3 adverse events makes it a reasonable option for this population.