title: Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807).
abstract: We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m(2) [dose level (DL)1] or 40 mg/m(2) [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m(2) cisplatin, day 1; 800 mg/m(2) fluorouracil, days 1-5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48-75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737.
authors.affiliation: Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hironaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsubosa
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kii
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsushima
authors.forename: Keisho
authors.initials: K
authors.lastname: Chin
authors.forename: Akihisa
authors.initials: A
authors.lastname: Tomori
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Taniki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Matsushita
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kusaba
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fujitani
authors.forename: Koichi
authors.initials: K
authors.lastname: Taira
authors.forename: Shiko
authors.initials: S
authors.lastname: Seki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil
keywords: 2-weekly docetaxel; Chemotherapy; DCF therapy; metastatic esophageal cancer; phase I/II