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Article

Clinical and molecular assessment of regorafenib monotherapy

  • Authors:
    • Nao Kakizawa
    • Koichi Suzuki
    • Taro Fukui
    • Yuji Takayama
    • Kosuke Ichida
    • Yuta Muto
    • Fumi Hasegawa
    • Fumiaki Watanabe
    • Rina Kikugawa
    • Shingo Tsujinaka
    • Kazushige Futsuhara
    • Yasuyuki Miyakura
    • Hiroshi Noda
    • Toshiki Rikiyama
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Saitama Medical Center, Jichi Medical University, Omiya-ku, Saitama 330-8503, Japan
  • Pages: 2506-2512
    |
    Published online on: February 15, 2017
       https://doi.org/10.3892/or.2017.5456
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Kakizawa N, Suzuki K, Fukui T, Takayama Y, Ichida K, Muto Y, Hasegawa F, Watanabe F, Kikugawa R, Tsujinaka S, Tsujinaka S, et al: Clinical and molecular assessment of regorafenib monotherapy. Oncol Rep 37: 2506-2512, 2017.
APA
Kakizawa, N., Suzuki, K., Fukui, T., Takayama, Y., Ichida, K., Muto, Y. ... Rikiyama, T. (2017). Clinical and molecular assessment of regorafenib monotherapy. Oncology Reports, 37, 2506-2512. https://doi.org/10.3892/or.2017.5456
MLA
Kakizawa, N., Suzuki, K., Fukui, T., Takayama, Y., Ichida, K., Muto, Y., Hasegawa, F., Watanabe, F., Kikugawa, R., Tsujinaka, S., Futsuhara, K., Miyakura, Y., Noda, H., Rikiyama, T."Clinical and molecular assessment of regorafenib monotherapy". Oncology Reports 37.4 (2017): 2506-2512.
Chicago
Kakizawa, N., Suzuki, K., Fukui, T., Takayama, Y., Ichida, K., Muto, Y., Hasegawa, F., Watanabe, F., Kikugawa, R., Tsujinaka, S., Futsuhara, K., Miyakura, Y., Noda, H., Rikiyama, T."Clinical and molecular assessment of regorafenib monotherapy". Oncology Reports 37, no. 4 (2017): 2506-2512. https://doi.org/10.3892/or.2017.5456
Copy and paste a formatted citation
x
Spandidos Publications style
Kakizawa N, Suzuki K, Fukui T, Takayama Y, Ichida K, Muto Y, Hasegawa F, Watanabe F, Kikugawa R, Tsujinaka S, Tsujinaka S, et al: Clinical and molecular assessment of regorafenib monotherapy. Oncol Rep 37: 2506-2512, 2017.
APA
Kakizawa, N., Suzuki, K., Fukui, T., Takayama, Y., Ichida, K., Muto, Y. ... Rikiyama, T. (2017). Clinical and molecular assessment of regorafenib monotherapy. Oncology Reports, 37, 2506-2512. https://doi.org/10.3892/or.2017.5456
MLA
Kakizawa, N., Suzuki, K., Fukui, T., Takayama, Y., Ichida, K., Muto, Y., Hasegawa, F., Watanabe, F., Kikugawa, R., Tsujinaka, S., Futsuhara, K., Miyakura, Y., Noda, H., Rikiyama, T."Clinical and molecular assessment of regorafenib monotherapy". Oncology Reports 37.4 (2017): 2506-2512.
Chicago
Kakizawa, N., Suzuki, K., Fukui, T., Takayama, Y., Ichida, K., Muto, Y., Hasegawa, F., Watanabe, F., Kikugawa, R., Tsujinaka, S., Futsuhara, K., Miyakura, Y., Noda, H., Rikiyama, T."Clinical and molecular assessment of regorafenib monotherapy". Oncology Reports 37, no. 4 (2017): 2506-2512. https://doi.org/10.3892/or.2017.5456
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