Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen).
Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m(2) (3 patients), 65 mg/m(2) (6 patients), and 75 mg/m(2) (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m(2) (grade 4 leukopenia) and in 3 patients at 75 mg/m(2) (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m(2), d 1; leucovorin 200 mg/m(2), 2 h, d1-2; 5-fluorouracil 400 mg/m(2), iv, d 1-2 and 600 mg/m(2) civ, 22 h, d 1-2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.
Division of Abdominal Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Xin
X
Wang
Yongsheng
Y
Wang
Meng
M
Qiu
Qiu
Q
Li
Zhi-ping
ZP
Li
Bing
B
He
Feng
F
Xu
Ya-li
YL
Shen
Hong-feng
HF
Gou
Yu
Y
Yang
Dan
D
Cao
Cheng
C
Yi
Ji-yan
JY
Liu
De-yun
DY
Luo
Zheng-yin
ZY
Liao
Feng
F
Bi
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005743:Gastrectomy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D013274:Stomach Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil