A multicenter phase I study of preoperative chemoradiotherapy with S-1 and irinotecan for locally advanced lower rectal cancer (SAMRAI-1).
Preoperative 5-fluorouracil-based chemoradiotherapy is a standard treatment for locally advanced lower rectal cancer (LALRC). We performed a phase I study to develop a new regimen combining irinotecan and S-1.



Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45Gy in 25 fractions. S-1 (80mg/m(2)/day) was administered on days 1-5, 8-12, 22-26, and 29-33. Irinotecan was administered on days 1, 8, 22, and 29. The dose of irinotecan was initially 60mg/m(2) (level 1). Surgery was performed 6-10weeks after the chemoradiotherapy.



Twenty patients were enrolled, of whom 18 patients were analyzed. Dose-limiting toxicity (DLT) did not occur in the first 3 patients treated with irinotecan at 80mg/m(2) (level 2), but developed in 3 of the 6 patients who received irinotecan at 90mg/m(2) (level 3). Then DLT occurred in 3 other patients at level 2. At level 2 or 3, DLT comprised neutropenia, thrombocytopenia, and diarrhea. Level 2 was designated as the maximum tolerated dose, and level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the down-staging rate was 56%.



Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60mg/m(2).
Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan.
Takeo
T
Sato
Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Japan.
Kazushige
K
Hayakawa
Division of Lower GI, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Naohiro
N
Tomita
Division of Lower GI, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Masafumi
M
Noda
Department of Radiology, Hyogo College of Medicine, Nishinomiya, Japan.
Norihiko
N
Kamikonya
Department of Surgical Oncology, The University of Tokyo Graduate School of Medicine and Faculty of Medicine, Japan.
Toshiaki
T
Watanabe
Department of Radiation Therapy, Kawasaki Saiwai Hospital, Japan.
Daiki
D
Kato
Department of Surgery, Kyoto University Graduate School of Medicine, Japan.
Yoshiharu
Y
Sakai
Department of Radiation Oncology & Image-applied Radiology, Kyoto University Graduate School of Medicine, Japan.
Masahiro
M
Hiraoka
Department of Surgery, The University of Tokushima Graduate School, Japan.
Mitsuo
M
Shimada
Department of Radiation Therapy Technology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
Hitoshi
H
Ikushima
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Japan.
Hideo
H
Baba
Faculty of Life Sciences, Department of Radiation Oncology, Graduate School of Medical Sciences, Kumamoto University, Japan.
Natsuo
N
Oya
Department of Surgery, Koshigaya Hospital, Dokkyo Medical University, Japan.
Masatoshi
M
Oya
Radiation Oncology Department, The Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan.
Keiko
K
Nemoto-Murofushi
Department of Clinical Medicine, Kitasato University School of Pharmacy, Tokyo, Japan.
Masahiro
M
Takeuchi
Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan. Electronic address: intl-aff@kitasato-u.ac.jp.
Masahiko
M
Watanabe
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014057:Tomography, X-Ray Computed
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin
Irinotecan; Neoadjuvant chemoradiotherapy; Rectal cancer; S-1