A phase I trial of S-1 with oxaliplatin in patients with relapsed and metastatic colorectal cancer.
OBJECTIVE
S-1 showed clinical activity in colorectal cancer, and the preclinical data of S-1 with oxaliplatin showed synergistic activity in an animal model. This phase I study was conducted to determine the maximum tolerated dose of S-1 with oxaliplatin and to define its recommended dose for the subsequent phase II study.


METHODS
Patients with untreated colorectal adenocarcinoma were eligible in this study if they had measurable lesions. S-1 was administered on days 1-14, with doses starting from 60 mg/m2 per day and escalating by 10 mg/m2 at each dose level. Oxaliplatin was given at the fixed dose of 130 mg/m2, through 2-h i.v. infusion on day 1. The treatment was repeated every 3 weeks.


RESULTS
A total of 27 patients received six different S-1 dose levels. The dose-limiting toxicities (DLTs) were neutropenia, diarrhea, and vomiting. At dose level 5 (100 mg/m2), two patients experienced DLTs, while none of the third cohorts did. At dose level 6 (110 mg/m2), two patients experienced DLTs, and one of them died from treatment-related toxicity. The accrual was then stopped.


CONCLUSIONS
The recommended dose is S-1 100 mg/m2 on days 1-14, with 130 mg/m2 oxaliplatin on day 1, every 3 weeks. This regimen is proposed for the phase II study.
Kim
Hyeong Su
HS
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea.
Park
Min Jae
MJ
Uhm
Ji Eun
JE
Lee
Yuna
Y
Lee
Hui Young
HY
Kang
Eun Mi
EM
Lee
Jeeyun
J
Park
Se Hoon
SH
Park
Joon Oh
JO
Lim
Ho Yeong
HY
Kang
Won Ki
WK
Park
Young Suk
YS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid