Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:30023.

A phase II trial of 1st-line modified-FOLFOXIRI plus bevacizumab treatment for metastatic colorectal cancer harboring RAS mutation: JACCRO CC-11

Hironaga Satake, Yu Sunakawa _, Yuji Miyamoto, Masato Nakamura, Hiroshi Nakayama, Manabu Shiozawa, Akitaka Makiyama, Kazuma Kobayashi, Yutaro Kubota, Misuzu Mori, Masahito Kotaka, Akinori Takagane, Masahiro Gotoh, Masahiro Takeuchi, Masashi Fujii, Wararu Ichikawa and Takashi Sekikawa

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Oncotarget. 2018; 9:18811-18820. https://doi.org/10.18632/oncotarget.24702

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Hironaga Satake1,*, Yu Sunakawa2,*, Yuji Miyamoto3, Masato Nakamura4, Hiroshi Nakayama5, Manabu Shiozawa6, Akitaka Makiyama7, Kazuma Kobayashi8, Yutaro Kubota9, Misuzu Mori10, Masahito Kotaka11, Akinori Takagane12, Masahiro Gotoh13, Masahiro Takeuchi14, Masashi Fujii15, Wararu Ichikawa16 and Takashi Sekikawa16

1Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo, 650-0047, Japan

2Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, 216-8511, Japan

3Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 860-8556, Japan

4Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Nagano, 390-8510, Japan

5Department of Surgery, Nagoya Medical Center, Nagoya, Aichi, 460-0001, Japan

6Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, 241-0815, Japan

7Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyusyu, Fukuoka, 806-8501, Japan

8Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan

9Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Shinagawa-Ku, Tokyo, 142-8666, Japan

10Division of Clinical Oncology, Jichi Medical University, Shimotsuke-Shi, Tochigi, 329-0498, Japan

11Gastrointestinal Cancer Center, Sano Hospital, Kobe, Hyogo, 655-0031, Japan

12Department of Surgery, Hakodate Goryoukaku Hospital, Hakodate, Hokkaido, 040-8611, Japan

13Cancer Chemotherapy Center, Osaka Medical College Hospital, Takatsuki, Osaka, 569-8686, Japan

14Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Minato-ku, Tokyo, 108-8641, Japan

15Department of Digestive Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo, 173-8610, Japan

16Division of Medical Oncology, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, 227-8501, Japan

*These authors have contributed equally to this work

Correspondence to:

Yu Sunakawa, email: [email protected]

Keywords: FOLFOXIRI; bevacizumab; colorectal cancer; RAS mutant; sidedness

Received: January 15, 2018     Accepted: March 06, 2018     Published: April 10, 2018


FOLFOXIRI plus bevacizumab is considered a standard initial therapy for metastatic colorectal cancer (mCRC). However, few prospective trials have evaluated triplet therapy plus bevacizumab in patients with RAS mutant mCRC. Patients with an age of 20 to 75 years, and unresectable, measurable tumors harboring RAS mutation were given first-line treatment with bevacizumab (5 mg/kg on day 1) plus modified-FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, levofolinate 200 mg/m2, and fluorouracil 2400 mg/m2 as a 46-h continuous infusion on day 1, repeated every 2 weeks). The primary endpoint was the objective response rate (ORR) as evaluated by an external review board. Progression-free survival (PFS), overall survival, early tumor shrinkage (ETS), depth of response (DpR), and safety were secondary endpoints. Among 64 patients who were enrolled between October 2014 and August 2016, 62 were evaluable for efficacy (right-sided tumors in 27%). ORR and disease control rate were 75.8% (95% confidence interval [CI] 65.1-86.5) and 96.8%, respectively. ETS was 73.8%, and median DpR was 49.2%. Median PFS was 11.5 (95% CI 9.5-14.0) months as of the cut-off date of September 2017. Adverse events of grade 3 or 4 were neutropenia (54%), hypertension (32%), diarrhea (13%), anorexia (11%), peripheral neuropathy (2%), and febrile neutropenia (5%). In conclusion, this prospective trial demonstrated for the first time that FOLFOXIRI plus bevacizumab is an active first-line treatment for patients with RAS mutant mCRC. Modified-FOLFOXIRI plus bevacizumab might become an alternative regimen of triplet chemotherapy for mCRC in Japan.

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