Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian cancer: a phase 3, double-blind, parallel group, randomized controlled pilot study.

backgroundChemotherapeutic agents for ovarian cancer commonly cause chemotherapy-induced peripheral neuropathy (CIPN), significantly impairing quality of life (QoL). Selenium, a potent antioxidant, may mitigate toxicity and improve QoL in cancer patients. This study evaluated intravenous high-dose selenium for preventing neuropathic symptoms in platinum-sensitive recurrent ovarian cancer (PSROC).

methodsA phase 3, double-blind, parallel group, randomized controlled pilot trial enrolled 68 patients with PSROC, randomized 1:1 to the experimental (selenium) and control (placebo) groups. Patients received sodium selenite pentahydrate (2000 µg /40 mL) or normal saline intravenously two hours before paclitaxel-carboplatin-bevacizumab infusion for six cycles. The primary endpoint was the incidence of grade 1 or more CIPN at 3 months following six cycles of chemotherapy, comparing the experimental group to the control group. Secondary endpoints included comparisons of grade 1 or more, grade 2 or more CIPN before each cycle, 3 weeks and 3 months after six cycles of chemotherapy, adverse events, QoL, and the need for concomitant medications to manage CIPN, and survival between the two groups.

resultsWe enrolled sixty-eight patients in the study. The incidence of grade 1 or more CIPN did not differ between the two groups at 3 months post-chemotherapy. However, grade 2 or motor dysfunction incidence was significantly lower in the experimental group before cycle 3 (3.3% vs. 23.3%; P = 0.02) and before cycle 4 (3.3% vs. 20%; P = 0.04), particularly in patients ≥ 60 years. QoL showed no statistically significant difference between the two groups. Duloxetine/gabapentin usage and adverse events were comparable between the two groups, with no selenium-related toxicity, and there were no differences in progression-free and cancer-specific survivals between the two groups.

conclusionsIntravenous high-dose selenium safely failed to reduce grade 1 or more CIPN, whereas it reduced grade 2 or more motor dysfunction during chemotherapy in patients with PSROC, especially those ≥ 60 years. While the primary endpoint was not met, selenium showed the potential of protective effects against motor neuropathy without safety and survival concerns.

trial registrationClinicalTrials.gov Identifier: NCT04201561.