Neutropenia as a Predictive Factor in Metastatic Colorectal Cancer Treated With TAS-102

Clin Colorectal Cancer. 2017 Mar;16(1):51-57. doi: 10.1016/j.clcc.2016.07.005. Epub 2016 Jul 21.

Abstract

Background: TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common treatment-related adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The potential predictive value of neutropenia caused by cytotoxic drugs has been reported in various types of cancer.

Methods: We retrospectively analyzed 95 consecutive patients with metastatic colorectal cancer who received TAS-102 at 2 Japanese institutions between May 2014 and May 2015. To evaluate the association between efficacy and neutropenia, patients were divided into 4 categories according to the grade of neutropenia during the first cycle of TAS-102: Category A (grade 0-1), B (grade 2-4), C (grade 0-2), and D (grade 3-4).

Results: Patient characteristics were as follows: median age, 64 years; male, 58%; Eastern Cooperative Oncology Group performance status 0 to 1, 91%; primary site colon, 49%; KRAS exon 2 wild, 57%; and number of metastatic site ≥ 3, 55%. The disease control rate was significantly different between Category A and B (29.2% vs. 52.6%; P = .045) and between Category C and D (30.9% vs. 72.2%; P = .002). In multivariate analysis, Category D remained a significant predictive factor for progression-free survival compared with Category C (4.3 vs. 2.0 months; hazard ratio, 0.45; P = .01).

Conclusion: Neutropenia caused by TAS-102 during the first cycle was associated with better efficacy. Neutropenia may be a surrogate marker for adequate antitumor doses of TAS-102.

Keywords: Chemotherapy; Metastatic colorectal cancer; Neutropenia; Predictive factor; TAS-102.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / secondary
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neutropenia / chemically induced*
  • Prognosis
  • Pyrrolidines
  • Retrospective Studies
  • Thymine
  • Trifluridine / administration & dosage
  • Trifluridine / adverse effects*
  • Uracil / administration & dosage
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Pyrrolidines
  • trifluridine tipiracil drug combination
  • Uracil
  • Thymine
  • Trifluridine