Efficacy of Oral Nano-Silymarin Formulation Efficacy in the Prevention of  Bone Marrow Suppression Induced by XELOX or m-FOLFOX6 Regimens in  Metastatic Colorectal Cancer

Hedyieh  Karbasforooshan; Hossein  Rahimi; Omid  Arasteh; Abolghasem  Allahyari; Mehdi  varmaghani; Sepideh  Elyasi

doi:10.18502/jpc.v13i3.20318

Hedyieh Karbasforooshan Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Hossein Rahimi Department of Internal Medicine, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
Omid Arasteh Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Abolghasem Allahyari Department of Hematology-Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Mehdi varmaghani Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Sepideh Elyasi Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

DOI: https://doi.org/10.18502/jpc.v13i3.20318

Keywords: Nano-Silymarin; Metastatic Colorectal Cancer; XELOX; m-FOLFOX6; Bone Marrow Suppression

Abstract

Background: Bone marrow suppression (BMS) is one of the main complications of chemotherapeutic agents. Given its anti-inflammatory, anti-oxidant, and anti-apoptotic properties, silymarin, a flavonoid derived from Silybum marianum, has been used against chemotherapy-induced BMS. The purpose of this research was to elucidate the advantages of oral nano-silymarin as a supplement to XELOX (oxaliplatin and capecitabine) or m-FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) regimen in relieving BMS in patients with metastatic colorectal cancer.

Methods: A clinical trial was conducted on 60 individuals through a randomized, triple-blinded, placebo-controlled design. The participants received 70 mg capsules with 15% silymarin nano micelles or placebo capsules, twice daily after meals for the duration of six courses of XELOX or m-FOLFOX6, starting from the first day of treatment. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5 was applied to evaluate the grade of BMS following the third and sixth chemotherapy cycles.

Results: The nano-silymarin group had significantly lower median CTCAE scores for both thrombocytopenia and neutropenia at the end of the third course (P<0.001). However, the difference remained significant only for neutropenia at the end of the sixth course (P<0.001). On the other hand, nano-silymarin did not have protective effects against anemia. Moreover, based on the frequency of CTCAE grading scores, the differences remained significant until the end of the study for thrombocytopenia and neutropenia, but just until the end of the third course for anemia.

Conclusion: Nano-silymarin may display preventive effects against chemotherapy-induced bone marrow suppression, particularly neutropenia and thrombocytopenia in patients with metastatic colorectal cancer. However, further studies with larger sample sizes are required.