Akihito Tsuji1, Yu Sunakawa2, Wataru Ichikawa3, Masato Nakamura4, Mitsugu Kochi5, Tadamichi Denda6, Tatsuro Yamaguchi7, Ken Shimada8, Akinori Takagane9, Satoshi Tani10, Masahito Kotaka11, Hidekazu Kuramochi12, Kaoru Furushima13, Junichi Koike14, Yutaka Yonemura15, Masahiro Takeuchi16, Masashi Fujii5, Toshifusa Nakajima17. 1. 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. 2. Division of Medical Oncology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-chuo, Tsuzuki-ku, Yokohama, Kanagawa, 224-8503, Japan. 3. Division of Medical Oncology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa, 227-8501, Japan. wataru@med.showa-u.ac.jp. 4. Aizawa Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjyo, Matsumoto, Nagano, 390-8510, Japan. 5. Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan. 6. Division of Gastroenterology, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan. 7. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. 8. Division of Medical Oncology, Department of Internal Medicine, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-ku, Tokyo, 135-8577, Japan. 9. Department of Surgery, Hakodate Goryoukaku Hospital, 38-3, Goryokaku-machi, Hakodate, Hokkaido, 040-8611, Japan. 10. Department of Internal Medicine, Konan Hospital, 1-5-16, Kamokogahara, Higashinada-ku, Kobe, Hyogo, 658-0064, Japan. 11. Gastrointestinal Cancer Center, Sano Hospital, 2-5-1, Shimizugaoka, Tarumi-ku, Kobe, Hyogo, 655-0031, Japan. 12. Department of gastroenterological Surgery, Tokyo Women's Medical University Yachiyo Medical Center, 477-96, Owadashinden, Yachiyo, Chiba, 276-8524, Japan. 13. Department of Surgery, NTT Medical Center, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan. 14. Department of Digestive Surgery, Toho University School of Medicine, 6-11-1, Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan. 15. Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamoricho, Kishiwada, Osaka, 596-0042, Japan. 16. Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan. 17. Japan Clinical Cancer Research Organization, 7F Ginza Wing Bldg. 1-14-5, Ginza, Chuo-ku, Tokyo, 104-0061, Japan.
Abstract
BACKGROUND: Retrospective studies have found that early tumor shrinkage (ETS) and depth of response (DpR) are associated with favorable outcomes in patients with metastatic colorectal cancer (mCRC); however, few prospective studies have evaluated ETS and DpR. PATIENTS AND METHODS: We performed a phase II study of FOLFOX plus cetuximab as first-line treatment in Japanese patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), chronological tumor shrinkage (evaluated every 8 weeks), and safety. The association of ETS and DpR with survival time was analyzed using Spearman's rank correlation coefficient. RESULTS: In 54 participants, the RR, median PFS, and OS were 66.7 % (95 % CI, 53.4-77.8 %), 11.1 months, and 33.9 months, respectively. There was no unexpected toxicity. Forty (80 %) of 50 assessable patients had ETS, which was associated with prolonged PFS and OS (11.3 vs. 3.7 months, HR 0.26, p = 0.0003; 42.8 vs. 9.0 months, HR 0.40, p = 0.0279, respectively). Median DpR was 56.3 %. The DpR correlated with OS (r s = 0.314, p = 0.027) as well as post-progression survival (PPS) (r s = 0.366, p = 0.017). Interestingly, DpR was moderately associated with OS and PPS (r s = 0.587, r s = 0.570, respectively) in patients harboring tumors with larger target lesions, but was not associated with OS or PPS in patients with smaller target lesions. FOLFOX plus cetuximab was active as a first-line treatment for Japanese mCRC patients, with no unexpected toxicities. CONCLUSIONS: Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy (UMIN000004197).
BACKGROUND: Retrospective studies have found that early tumor shrinkage (ETS) and depth of response (DpR) are associated with favorable outcomes in patients with metastatic colorectal cancer (mCRC); however, few prospective studies have evaluated ETS and DpR. PATIENTS AND METHODS: We performed a phase II study of FOLFOX plus cetuximab as first-line treatment in Japanese patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), chronological tumor shrinkage (evaluated every 8 weeks), and safety. The association of ETS and DpR with survival time was analyzed using Spearman's rank correlation coefficient. RESULTS: In 54 participants, the RR, median PFS, and OS were 66.7 % (95 % CI, 53.4-77.8 %), 11.1 months, and 33.9 months, respectively. There was no unexpected toxicity. Forty (80 %) of 50 assessable patients had ETS, which was associated with prolonged PFS and OS (11.3 vs. 3.7 months, HR 0.26, p = 0.0003; 42.8 vs. 9.0 months, HR 0.40, p = 0.0279, respectively). Median DpR was 56.3 %. The DpR correlated with OS (r s = 0.314, p = 0.027) as well as post-progression survival (PPS) (r s = 0.366, p = 0.017). Interestingly, DpR was moderately associated with OS and PPS (r s = 0.587, r s = 0.570, respectively) in patients harboring tumors with larger target lesions, but was not associated with OS or PPS in patients with smaller target lesions. FOLFOX plus cetuximab was active as a first-line treatment for Japanese mCRC patients, with no unexpected toxicities. CONCLUSIONS: Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy (UMIN000004197).
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