PMID- 28259999
OWN - NLM
STAT- MEDLINE
DCOM- 20170417
LR  - 20170417
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 37
IP  - 4
DP  - 2017 Apr
TI  - Clinical and molecular assessment of regorafenib monotherapy.
PG  - 2506-2512
LID - 10.3892/or.2017.5456 [doi]
AB  - Regorafenib has shown survival benefits in metastatic colorectal cancer patients 
      who were exacerbated after all standard therapies. Some patients, however, 
      exhibit severe adverse events (AEs) resulting in treatment discontinuation. 
      Therefore, the selection of patients likely to benefit from regorafenib is 
      crucial. Twenty patients were treated with regorafenib for metastatic colorectal 
      cancer; 122 plasma samples were taken from 16 of these patients for monitoring of 
      circulating tumor DNA (ctDNA) in the blood. The treatment response, AEs, overall 
      survival (OS), progression-free survival (PFS) and tumor morphologic changes on 
      CT images were evaluated. KRAS mutant ctDNA was determined using digital PCR. 
      Median PFS and OS were 2.5 and 5.9 months, respectively. Treatment was 
      discontinued because of disease progression (PD) in 10 patients, and AEs in 
      another 10 patients. AEs included hyperbilirubinemia, severe fatigue and skin 
      rash. Hyperbilirubinemia was seen in two patients with multiple bilateral liver 
      metastases, and severe fatigue in another 2 patients with poor performance status 
      (PS). These severe AEs resulted in treatment discontinuation. Ten patients had a 
      median PFS of 2.1 months with AE related discontinuation; PD occurred at 3.5 
      months (p=0.00334). Four patients exhibited a morphologic response, achieving 
      better PFS times of 3.5, 5.3, 5.6 and 14.2 months. Emergence of the KRAS mutation 
      in ctDNA was observed during anti-EGFR antibody treatment in 3 patients among 11 
      with KRAS wild-type tumors; it was detectable in the blood prior to radiographic 
      detection of PD. Moreover, the KRAS mutation declined in two patients during 
      regorafenib monotherapy. These patients were re-challenged with anti-EGFR 
      antibody. Patients with extensive multiple liver metastases or poor PS are 
      unlikely to benefit from regorafenib. Patients with a morphologic response will 
      probably benefit from regorafenib with adequate management of other AEs. KRAS 
      monitoring in ctDNA could be useful regarding treatment response and in 
      determining treatment strategy.
FAU - Kakizawa, Nao
AU  - Kakizawa N
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Suzuki, Koichi
AU  - Suzuki K
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Fukui, Taro
AU  - Fukui T
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Takayama, Yuji
AU  - Takayama Y
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Ichida, Kosuke
AU  - Ichida K
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Muto, Yuta
AU  - Muto Y
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Hasegawa, Fumi
AU  - Hasegawa F
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Watanabe, Fumiaki
AU  - Watanabe F
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Kikugawa, Rina
AU  - Kikugawa R
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Tsujinaka, Shingo
AU  - Tsujinaka S
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Futsuhara, Kazushige
AU  - Futsuhara K
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Miyakura, Yasuyuki
AU  - Miyakura Y
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Noda, Hiroshi
AU  - Noda H
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
FAU - Rikiyama, Toshiki
AU  - Rikiyama T
AD  - Department of Surgery, Saitama Medical Center, Jichi Medical University, 
      Omiya-ku, Saitama 330-8503, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170215
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (KRAS protein, human)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 24T2A1DOYB (regorafenib)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Colorectal Neoplasms/diagnostic imaging/*drug therapy/genetics
MH  - DNA, Neoplasm/*blood
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Metastasis
MH  - Phenylurea Compounds/*administration & dosage/adverse effects
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Pyridines/*administration & dosage/adverse effects
MH  - Survival Analysis
MH  - Tomography, X-Ray Computed
MH  - Treatment Outcome
EDAT- 2017/03/06 06:00
MHDA- 2017/04/18 06:00
CRDT- 2017/03/06 06:00
PHST- 2016/09/05 00:00 [received]
PHST- 2017/01/30 00:00 [accepted]
PHST- 2017/03/06 06:00 [pubmed]
PHST- 2017/04/18 06:00 [medline]
PHST- 2017/03/06 06:00 [entrez]
AID - 10.3892/or.2017.5456 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Apr;37(4):2506-2512. doi: 10.3892/or.2017.5456. Epub 2017 Feb 15.