Early Tumor Shrinkage and Depth of Response as Predictors of Favorable Treatment Outcomes in Patients with Metastatic Colorectal Cancer Treated with FOLFOX Plus Cetuximab (JACCRO CC-05).
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.



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.



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 (rs= 0.314, p = 0.027) as well as post-progression survival (PPS) (rs= 0.366, p = 0.017). Interestingly, DpR was moderately associated with OS and PPS (rs= 0.587, rs= 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.



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).
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.
Akihito
A
Tsuji
Division of Medical Oncology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-chuo, Tsuzuki-ku, Yokohama, Kanagawa, 224-8503, Japan.
Yu
Y
Sunakawa
Division of Medical Oncology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa, 227-8501, Japan. wataru@med.showa-u.ac.jp.
Wataru
W
Ichikawa
Aizawa Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjyo, Matsumoto, Nagano, 390-8510, Japan.
Masato
M
Nakamura
Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan.
Mitsugu
M
Kochi
Division of Gastroenterology, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan.
Tadamichi
T
Denda
Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
Tatsuro
T
Yamaguchi
Division of Medical Oncology, Department of Internal Medicine, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-ku, Tokyo, 135-8577, Japan.
Ken
K
Shimada
Department of Surgery, Hakodate Goryoukaku Hospital, 38-3, Goryokaku-machi, Hakodate, Hokkaido, 040-8611, Japan.
Akinori
A
Takagane
Department of Internal Medicine, Konan Hospital, 1-5-16, Kamokogahara, Higashinada-ku, Kobe, Hyogo, 658-0064, Japan.
Satoshi
S
Tani
Gastrointestinal Cancer Center, Sano Hospital, 2-5-1, Shimizugaoka, Tarumi-ku, Kobe, Hyogo, 655-0031, Japan.
Masahito
M
Kotaka
Department of gastroenterological Surgery, Tokyo Women's Medical University Yachiyo Medical Center, 477-96, Owadashinden, Yachiyo, Chiba, 276-8524, Japan.
Hidekazu
H
Kuramochi
Department of Surgery, NTT Medical Center, 5-9-22, Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.
Kaoru
K
Furushima
Department of Digestive Surgery, Toho University School of Medicine, 6-11-1, Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.
Junichi
J
Koike
Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamoricho, Kishiwada, Osaka, 596-0042, Japan.
Yutaka
Y
Yonemura
Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
Masahiro
M
Takeuchi
Department of Digestive Surgery, Nihon University School of Medicine, 30-1, Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan.
Masashi
M
Fujii
Japan Clinical Cancer Research Organization, 7F Ginza Wing Bldg. 1-14-5, Ginza, Chuo-ku, Tokyo, 104-0061, Japan.
Toshifusa
T
Nakajima
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D009944:Organoplatinum Compounds; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil