Phase I study of neoadjuvant chemoradiotherapy with S-1 and oxaliplatin in patients with locally advanced gastric cancer.
OBJECTIVE
The aim of this phase I study was to investigate the optimal dose of S-1 and oxaliplatin with concurrent radiotherapy in a preoperative setting for locally advanced gastric cancer.


METHODS
Twelve patients with histologically confirmed clinical stage T2N+ or T3-T4 gastric adenocarcinoma received dose level -1 (oral S-1 at 60 mg/m(2)/day + oxaliplatin 40 mg/m(2) intravenously on days 1, 8, 15 and 22) or dose level 1 (S-1 80 mg/m(2)/day + oxaliplatin 40 mg/m(2)), with concurrent radiotherapy at daily fractions of 1.8 Gy 5 days per week, to a total dose of 41.4 Gy. Surgical resection, including D2 dissection, was performed within 4 weeks after the last day of chemotherapy.


RESULTS
Chemoradiotherapy was generally well tolerated, with the most common dose-related grade 1 or 2 adverse events being anemia, nausea, vomiting, anorexia and abdominal pain. Two DLTs (prolonged thrombocytopenia and stomach perforation) were observed at dose level 1 (n = 6) and resulted in dose de-escalation to level -1. The recommended dose for future study is dose level -1, at which 1 of 6 patients developed grade 3 vomiting and anorexia. R0 resection was possible in 11 patients. Pathologic down-staging was observed in 6 patients, including one complete response. No clinically relevant postoperative complications occurred.


CONCLUSIONS
The activity of preoperative concurrent chemoradiotherapy with S-1 (60 mg/m(2)/day for 28 consecutive days) and oxaliplatin (40 mg/m(2) on days 1, 8, 15 and 22) will be explored more extensively in a phase II study in patients with locally advanced GC.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Kangnam-gu, Seoul 135-710, Korea.
Duk Joo
DJ
Lee
Tae Sung
TS
Sohn
Do Hoon
DH
Lim
Hee Kyung
HK
Ahn
Se Hoon
SH
Park
Jeeyun
J
Lee
Joon Oh
JO
Park
Young Suk
YS
Park
Ho Yeong
HY
Lim
Dong Il
DI
Choi
Kyoung Mee
KM
Kim
Min Gew
MG
Choi
Jae Hyung
JH
Noh
Jae Moon
JM
Bae
Sung
S
Kim
Byung Hoon
BH
Min
Won Ki
WK
Kang
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid