Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K-ras status for unresectable colorectal liver metastasis (BECK study).
BACKGROUND
Patients with colorectal liver metastasis (CRLM) might be down-staged by chemotherapy from an initially unresectable stage to a resectable stage. Because the tumor response to preoperative chemotherapy has been correlated with resection rate, the improved efficacy from the concept that only the patients without K-ras mutations receive an anti-EGFR antibody might be expected to increase the conversion rate. The purpose of this study is to evaluate the conversion rate from unresectable CRLM to complete resection.


METHODS
We conducted a multi-institutional phase II trial for unresectable CRLM. Patients received mFOLFOX6 with either bevacizumab (bev) or cetuximab (cet) based on K-ras status (UMIN000004310). Planned treatment was for six cycles during which tumors were assessed for resectability every three cycles. Patients whose disease was unresectable after six cycles switched their chemotherapy regimen from mFOLFOX6 to FOLFIRI. The primary endpoint was R0 resection rate.


RESULTS
Thirty-five patients with unresectable CRLM were enrolled. A total of 22/12 patients with K-ras wild-type/mutant (wt/mt) were treated with mFOLFOX6 plus cet/bev, respectively. The overall response rate was 64.7% (wt/mt; 77.3%/41.7%, P = 0.04). In 20 patients (58.8%), hepatectomy was performed according to protocol treatment, and the conversion rate was 72.7%/33.3% in wt/mt patients, respectively (P = 0.03). Finally, 23 patients (67.6%) underwent hepatectomy, and the conversion rate was 77.2%/50.0% in wt/mt patients (P = 0.09). The overall R0 resection rate was 47.1% (wt/mt; 50.0%/41.7%, P = 0.36).


CONCLUSIONS
This prospective study showed that combined chemotherapy based on K-ras status can facilitate conversion to resection in patients with unresectable CRLM.
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Etsuro
E
Hatano
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Masayuki
M
Okuno
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kojiro
K
Nakamura
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takamichi
T
Ishii
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Satoru
S
Seo
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kojiro
K
Taura
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kentaro
K
Yasuchika
Department of Surgery, Shiga Medical Center for Adults, Moriyama, Shiga, Japan.
Takefumi
T
Yazawa
Department of Surgery, Shiga Medical Center for Adults, Moriyama, Shiga, Japan.
Masazumi
M
Zaima
Department of Surgery, Osaka Red Cross Hospital, Osaka, Japan.
Akiyoshi
A
Kanazawa
Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Osaka, Japan.
Hiroaki
H
Terajima
Department of Surgery, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
Satoshi
S
Kaihara
Department of Surgery, Saiseikai Noe Hospital, Osaka, Japan.
Yukihito
Y
Adachi
Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan.
Naoya
N
Inoue
Department of Surgery, Kishiwada City Hospital, Kishiwada, Osaka, Japan.
Katsuyoshi
K
Furumoto
Department of Surgery, Kyoto Katsura Hospital, Kyoto, Japan.
Dai
D
Manaka
Department of Surgery, Shimane Prefectural Central Hospital, Izumo, Shimane, Japan.
Atsuo
A
Tokka
Department of Surgery, Tenri Yorozu Hospital, Tenri, Nara, Japan.
Hiroaki
H
Furuyama
Department of Surgery, Fukui Red Cross Hospital, Fukui, Japan.
Koji
K
Doi
Department of Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan.
Tetsuro
T
Hirose
Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan.
Takahiro
T
Horimatsu
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Suguru
S
Hasegawa
Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan.
Shigemi
S
Matsumoto
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yoshiharu
Y
Sakai
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Shinji
S
Uemoto
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068818:Cetuximab / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D011905:Genes, ras; D006498:Hepatectomy; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011446:Prospective Studies
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
Colorectal liver metastasis; Conversion; Hepatic resection; Resectability