Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage II/III rectal cancer: the FACT trial.
A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6).



Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m2+ leucovorin at 200 mg/m2+ fluorouracil as a 400 mg/m2bolus followed by infusion of 2400 mg/m2over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician.



mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3-4 were neutropenia (n = 5), leukopenia (n = 1), thrombocytopenia (n = 1), febrile neutropenia (n = 1), nausea (n = 1), vomiting (n = 1), and peripheral neuropathy (n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable.



The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer.
Department of Gastroenterological Surgery, Omori Medical Center, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan. jkoike18@med.toho-u.ac.jp.|FACT Trial Group, Tokyo, Japan. jkoike18@med.toho-u.ac.jp.
Junichi
J
Koike
Department of Gastroenterological Surgery, Omori Medical Center, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.|FACT Trial Group, Tokyo, Japan.
Kimihiko
K
Funahashi
Department of Surgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Kazuhiko
K
Yoshimatsu
Department of Surgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Hajime
H
Yokomizo
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Hayato
H
Kan
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Takeshi
T
Yamada
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.|FACT Trial Group, Tokyo, Japan.
Hideyuki
H
Ishida
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.|FACT Trial Group, Tokyo, Japan.
Keiichiro
K
Ishibashi
Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Yoshihisa
Y
Saida
Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Toshiyuki
T
Enomoto
Department of Digestive Surgery and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Kenji
K
Katsumata
Department of Digestive Surgery and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Masayuki
M
Hisada
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Hirotoshi
H
Hasegawa
Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.|FACT Trial Group, Tokyo, Japan.
Keiji
K
Koda
Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Takumi
T
Ochiai
Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Kazuhiro
K
Sakamoto
Department of Gastroenterological Surgery, Omori Medical Center, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.|FACT Trial Group, Tokyo, Japan.
Hiroyuki
H
Shiokawa
Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Shimpei
S
Ogawa
Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Michio
M
Itabashi
Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.|FACT Trial Group, Tokyo, Japan.
Shingo
S
Kameoka
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011183:Postoperative Complications / Q000453:epidemiology; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D014057:Tomography, X-Ray Computed
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil
Neoadjuvant chemotherapy; Preoperative chemotherapy; Rectal cancer; Resectable; mFOLFOX6