title: Neutropenia as a Predictive Factor in Metastatic Colorectal Cancer Treated With TAS-102.
abstract: 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.
  
  
  
  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).
  
  
  
  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).
  
  
  
  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.
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Satoshi
authors: S
authors: Hamauchi
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. Electronic address: k.yamazaki@scchr.jp.
authors: Kentaro
authors: K
authors: Yamazaki
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Toshiki
authors: T
authors: Masuishi
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Yosuke
authors: Y
authors: Kito
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Azusa
authors: A
authors: Komori
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Takahiro
authors: T
authors: Tsushima
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Yukiya
authors: Y
authors: Narita
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Akiko
authors: A
authors: Todaka
authors: Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Makoto
authors: M
authors: Ishihara
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Tomoya
authors: T
authors: Yokota
authors: Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Tsutomu
authors: T
authors: Tanaka
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Nozomu
authors: N
authors: Machida
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Shigenori
authors: S
authors: Kadowaki
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Akira
authors: A
authors: Fukutomi
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Takashi
authors: T
authors: Ura
authors: Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Yusuke
authors: Y
authors: Onozawa
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Masashi
authors: M
authors: Ando
authors: Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Masahiro
authors: M
authors: Tajika
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Kei
authors: K
authors: Muro
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Hirofumi
authors: H
authors: Yasui
authors: Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Keita
authors: K
authors: Mori
authors: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Hiroya
authors: H
authors: Taniguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011379:Prognosis; D011759:Pyrrolidines; D012189:Retrospective Studies; D013941:Thymine; D014271:Trifluridine / Q000008:administration & dosage / Q000009:adverse effects*; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D013941:Thymine; D014271:Trifluridine
keywords: Chemotherapy; Metastatic colorectal cancer; Neutropenia; Predictive factor; TAS-102