Etsuro Hatano1, Masayuki Okuno1, Kojiro Nakamura1, Takamichi Ishii1, Satoru Seo1, Kojiro Taura1, Kentaro Yasuchika1, Takefumi Yazawa2, Masazumi Zaima2, Akiyoshi Kanazawa3, Hiroaki Terajima4, Satoshi Kaihara5, Yukihito Adachi6, Naoya Inoue7, Katsuyoshi Furumoto8, Dai Manaka9, Atsuo Tokka10, Hiroaki Furuyama11, Koji Doi12, Tetsuro Hirose13, Takahiro Horimatsu14, Suguru Hasegawa1, Shigemi Matsumoto14, Yoshiharu Sakai1, Shinji Uemoto1. 1. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2. Department of Surgery, Shiga Medical Center for Adults, Moriyama, Shiga, Japan. 3. Department of Surgery, Osaka Red Cross Hospital, Osaka, Japan. 4. Department of Gastroenterological Surgery and Oncology, Kitano Hospital, Osaka, Japan. 5. Department of Surgery, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan. 6. Department of Surgery, Saiseikai Noe Hospital, Osaka, Japan. 7. Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan. 8. Department of Surgery, Kishiwada City Hospital, Kishiwada, Osaka, Japan. 9. Department of Surgery, Kyoto Katsura Hospital, Kyoto, Japan. 10. Department of Surgery, Shimane Prefectural Central Hospital, Izumo, Shimane, Japan. 11. Department of Surgery, Tenri Yorozu Hospital, Tenri, Nara, Japan. 12. Department of Surgery, Fukui Red Cross Hospital, Fukui, Japan. 13. Department of Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa, Japan. 14. Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan.
Abstract
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.
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.