Survival analyses of the ZeOxaNMulti trial: Follow-up randomized, double-blinded, placebo-controlled trial of oral PMA-zeolite to prevent chemotherapy-induced side effects, especially peripheral neuropathy
Authors: Vitale Maria Giuseppa , Crispo Anna , Arundine Dario , Ronga Riccardo , Barbato Carmela , Luongo Assunta , Habetswallner Francesco , De Martino Bernardo Maria , Maione Angela , Eisenwagen Sandra , Vitale Giovanna , Riccardi Ferdinando 
Published: November 2022

Following the previously published results of the clinical randomized ZeOxaNMulti trial, we evaluated the potential of the tested product PMA-ZEO (Multizeo Med) in the prevention of chemotherapy-induced side effects (especially peripheral neuropathy) within a 30-month follow-up analysis. The aim was to determine the disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) in a study-population suffering from colorectal cancer that was previously enrolled in the ZeOxaNMulti trial from April 2015 to October 2018. The participants of the study were randomized to receive either PMA-ZEO or placebo while undergoing oxaliplatin-based chemotherapy. A total of 104 patients (pts) (51% of participants randomized to the PMA-ZEO group and 49% to the placebo group), out of a total of 120 pts included in the ZeOxaNMulti trial in 2015, were followed up until March 2021 and were included in the follow-up analysis. According to the chemotherapy line, 44.2% of patients received chemotherapy in an adjuvant setting, and 55.8% of patients received chemotherapy as first-line treatment. The statistical analysis for DFS, PFS, and OS was performed by comparison of the end results with data from the PMA-ZEO/placebo-intervention start point. The analysis of OS did not show statistically significant differences in the first-line chemotherapy patients randomized to PMA-ZEO than among the placebo group (p = 0.1) over the whole period of follow-up (30 months). However, focusing on the PMA-ZEO supplementation time point (7 months), a positive and statistically significant trend (p = 0.004) was documented in the OS analysis for the first-line chemotherapy patients with increasing months of PMA-ZEO treatment compared to the placebo group. Furthermore, borderline statistical significance was reached for PFS at the PMA-ZEO supplementation time point (7 months) in the first-line chemotherapy patients (p = 0.05) for cancer progression events. After stratification of the first-line chemotherapy patients, statistically relevant trends for OS for age, comorbidities, and oxaliplatin dosage (cycles) were also determined. The overall results for DFS (adjuvant patients), PFS (first-line chemotherapy patients), and OS (adjuvant and first-line chemotherapy patients) were generally slightly better in the PMA-ZEO group than in the placebo group, even though no statistically significant results were obtained between the groups within the follow-up period until 2021 (30 months). Based on this follow-up analysis, protective effects of PMA-zeolite supplementation can be deduced. A positive trend and more importantly, significant results in PFS and OS for specific patient groups during and/or after PMA-ZEO treatment were determined, which supports the use of PMA-ZEO as an oncological supportive therapy.