A phase I trial of 5-fluorouracil with cisplatin and concurrent standard-dose radiotherapy in Japanese patients with stage II/III esophageal cancer.
OBJECTIVE
In Japan, 5-fluorouracil (5-FU) 400 mg/m(2) on Days 1-5, 8-12, 36-40 and 43-46 with cisplatin (CDDP) 40 mg/m(2) on Days 1, 8, 36 and 43 plus concurrent radiotherapy with 2 weeks planned interruption (60 Gy) was standard for the patients with esophageal cancer. This Phase I trial was designed to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of 5-FU on Days 1-4 and 29-32 with CDDP on Days 1 and 29 plus concurrent radiotherapy (50.4 Gy) among the Japanese.


METHODS
Escalating doses of 5-FU and CDDP were administered with concurrent radiotherapy (50.4 Gy). Treatment was continued until DLT appeared.


RESULTS
Twelve patients with previously untreated clinical Stage II/III squamous cell esophageal carcinoma were studied. One of six patients given Level 1 (5-FU 800 mg/m(2) on Days 1-4 and 29-32 with CDDP 75 mg/m(2) on Days 1 and 29) developed a DLT of incomplete protocol treatment due to Grade 3 esophagitis. The MTD was not reached at Level 2 (5-FU 1000 mg/m(2) with CDDP 75 mg/m(2)). The complete response rate was 67% at Level 1 and 100% at Level 2.


CONCLUSIONS
Dose Level 2 with 50.4 Gy radiotherapy was recommended for Japanese patients.
Nakajima
Takako Eguchi
TE
Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan. taeguchi@ncc.go.jp
Ura
Takashi
T
Ito
Yoshinori
Y
Kato
Ken
K
Minashi
Keiko
K
Nihei
Keiji
K
Hironaka
Shuichi
S
Boku
Narikazu
N
Kagami
Yoshikazu
Y
Muro
Kei
K
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging
D002945:Cisplatin; D005472:Fluorouracil