Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402)

Oncology. 2018;94(5):289-296. doi: 10.1159/000486624. Epub 2018 Mar 7.

Abstract

Background: Regorafenib is an oral multikinase inhibitor with a proven survival benefit for metastatic colorectal cancer patients. The KSCC1402/HGCSG1402 study investigated the prophylactic effect of oral dexamethasone (DEX) on regorafenib-related fatigue and/or malaise.

Patients and methods: Patients who progressed after standard chemotherapy were randomized 1: 1 to a DEX group (2 mg/day; days 1-28) with regorafenib or a placebo group with regorafenib. The primary endpoint was the incidence of fatigue and/or malaise, based on version 4.0 of the National Cancer Institute's CTCAE (Common Terminology Criteria for Adverse Events). One of the secondary endpoints was the in-cidence of fatigue and/or malaise based on the CTCAE assessed by patient-reported outcome (PRO).

Results: The incidence of any grade of fatigue and/or malaise assessed by the investigators was 58.8% in the DEX group and 61.1% in the placebo group (p = 0.8101), and that assessed by PRO was 47.2 and 58.3%, respectively (p = 0.3450). The incidence of grade ≥2 fatigue and/or malaise, as assessed by the investigators, was 19.4% for the DEX group and 38.9% for the placebo group (p = 0.0695), and that assessed by PRO was 27.8 and 52.8%, respectively (p = 0.0306).

Conclusion: Our results suggest that prophylactic oral DEX is clinically effective in improving regorafenib-related fatigue and/or malaise.

Keywords: Colorectal cancer; Dexamethasone; Fatigue; Malaise; Regorafenib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Chemoprevention*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / physiopathology
  • Dexamethasone / therapeutic use*
  • Double-Blind Method
  • Fatigue / chemically induced*
  • Fatigue / prevention & control
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Glucocorticoids
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • regorafenib
  • Dexamethasone