Yu Sunakawa1, Akihito Tsuji2, Tadamichi Denda3, Yoshihiko Segawa4, Yuji Negoro5, Ken Shimada6, Mitsugu Kochi7, Masato Nakamura8, Masahito Kotaka9, Hiroaki Tanioka10, Akinori Takagane11, Satoshi Tani12, Tatsuro Yamaguchi13, Takanori Watanabe14, Masahiro Takeuchi15, Masashi Fujii7, Wataru Ichikawa16. 1. Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 2168511, Japan. y.suna0825@gmail.com. 2. Department of Clinical Oncology, Kagawa University Faculty of Medicine Cancer Center, Kagawa University Hospital, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. 3. Division of Gastroenterology, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan. 4. Department of Medical Oncology, International Medical Center, Saitama Medical University, 1397-1 Yamane, Saitama, Hidaka, 350-1241, Japan. 5. Department of Gastroenterology, Kochi Health Sciences Center, 2125-1, Ike, Kochi, 781-8555, Japan. 6. Division of Medical Oncology, Department of Internal Medicine, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-ku, Tokyo, 135-8577, Japan. 7. Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan. 8. Aizawa Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjyo, Matsumoto, Nagano, 390-8510, Japan. 9. Gastrointestinal Cancer Center, Sano Hospital, 2-5-1, Shimizugaoka, Tarumi-ku, Kobe, Hyogo, 655-0031, Japan. 10. Department of Medical Oncology, Japan Labour Health and Welfare Organization Okayama Rosai Hospital, 1-10-25, Chikko Midori-machi, Minami-ku, Okayama, 702-8055, Japan. 11. Department of Surgery, Hakodate Goryoukaku Hospital, 38-3, Goryoukaku-machi, Hakodate, Hokkaido, 040-8611, Japan. 12. Department of Internal Medicine, Konan Hospital, 1-5-16, Kamokogahara, Higashinada-ku, Kobe, Hyogo, 658-0064, Japan. 13. Department of Surgery, Tokyo Metropolitan Cancer and Infections diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. 14. Department of Surgery, Himeji Red Cross Hospital, 1-21-1, Shimoteno, Himeji, Hyogo, 670-8540, Japan. 15. Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan. 16. Division of Medical Oncology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa, 227-8501, Japan.
Abstract
BACKGROUND: The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab. OBJECTIVE: We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment. PATIENTS AND METHODS: Associations among the CEA decrease, depth of response (DpR), and clinical outcomes were evaluated in 113 patients with mCRC from two phase II trials of first-line therapy: the JACCRO CC-05 trial of cetuximab plus FOLFOX and the CC-06 trial of cetuximab plus SOX. Analysis was performed using Spearman's rank correlation coefficient. A 75% decrease in the CEA was used as the cut-off value to define the CEA response and discriminate CEA responders on the basis of the results of a previous study. RESULTS: Ninety-two patients were eligible for analyses of both CEA and DpR. The median CEA decrease was 67.4%, and the median time to CEA nadir was 2.8 months, which was similar to the median time to DpR of 3.0 months. The DpR was associated with PFS and OS (rs = 0.56, P < 0.0001; rs = 0.39, P = 0.0090, respectively); moreover, the CEA decrease correlated with PFS (rs = 0.56, P < 0.0001), as well as OS (rs = 0.35, P = 0.019). CEA responders had significantly longer PFS (11.8 vs. 5.5 months, hazard ratio [HR] 0.46, P = 0.0009) and slightly, but not significantly longer OS (36.2 vs. 23.5 months; HR 0.57; P = 0.072) than CEA non-responders. The CEA decrease was statistically significantly associated with the DpR (rs = 0.44, P < 0.0001). CONCLUSIONS: Our study demonstrates that both DpR and CEA response correlate with clinical outcomes of first-line treatment with cetuximab. The CEA decrease may serve as a surrogate for DpR in patients who receive first-line cetuximab treatment (UMIN000004197, UMIN000007022).
BACKGROUND: The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab. OBJECTIVE: We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment. PATIENTS AND METHODS: Associations among the CEA decrease, depth of response (DpR), and clinical outcomes were evaluated in 113 patients with mCRC from two phase II trials of first-line therapy: the JACCRO CC-05 trial of cetuximab plus FOLFOX and the CC-06 trial of cetuximab plus SOX. Analysis was performed using Spearman's rank correlation coefficient. A 75% decrease in the CEA was used as the cut-off value to define the CEA response and discriminate CEA responders on the basis of the results of a previous study. RESULTS: Ninety-two patients were eligible for analyses of both CEA and DpR. The median CEA decrease was 67.4%, and the median time to CEA nadir was 2.8 months, which was similar to the median time to DpR of 3.0 months. The DpR was associated with PFS and OS (rs = 0.56, P < 0.0001; rs = 0.39, P = 0.0090, respectively); moreover, the CEA decrease correlated with PFS (rs = 0.56, P < 0.0001), as well as OS (rs = 0.35, P = 0.019). CEA responders had significantly longer PFS (11.8 vs. 5.5 months, hazard ratio [HR] 0.46, P = 0.0009) and slightly, but not significantly longer OS (36.2 vs. 23.5 months; HR 0.57; P = 0.072) than CEA non-responders. The CEA decrease was statistically significantly associated with the DpR (rs = 0.44, P < 0.0001). CONCLUSIONS: Our study demonstrates that both DpR and CEA response correlate with clinical outcomes of first-line treatment with cetuximab. The CEA decrease may serve as a surrogate for DpR in patients who receive first-line cetuximab treatment (UMIN000004197, UMIN000007022).
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