Phase I study of preoperative chemoradiation with s-1 and oxaliplatin in patients with locally advanced resectable rectal cancer.
OBJECTIVE
To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose.


METHODS
Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m2/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m2/day, gradually increasing to 60, 70, and 80 mg/m2/day. Surgery was performed within 6±2 weeks.


RESULTS
Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m2/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%).


CONCLUSIONS
The recommended dose of S-1 was determined to be 80 mg/m2/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.
Hong
Yong Sang
YS
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Lee
Jae-Lyun
JL
Park
Jin Hong
JH
Kim
Jong Hoon
JH
Yoon
Sang Nam
SN
Lim
Seok-Byung
SB
Yu
Chang Sik
CS
Kim
Mi-Jung
MJ
Jang
Se-Jin
SJ
Lee
Jung Shin
JS
Kim
Jin Cheon
JC
Kim
Tae Won
TW
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D009503:Neutropenia / Q000209:etiology / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D011300:Preoperative Care / Q000379:methods; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000209:etiology / Q000473:pathology; D014839:Vomiting / Q000209:etiology
D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid