Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003).
BACKGROUND
This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC.


METHODS
Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat.


RESULTS
Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively.


CONCLUSIONS
Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC.


BACKGROUND
University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka.
M
M
Yamasaki
Department of Surgery, Kinki University School of Medicine, Osaka Sayama, Osaka.
T
T
Yasuda
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka.
M
M
Yano
Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka.
M
M
Hirao
Department of Surgery, Kinki Central Hospital of the Mutual Aid Association of Public School Teachers, Hyogo.
K
K
Kobayashi
Department of Surgery, Osaka General Medical Center, Osaka.
K
K
Fujitani
Department of Surgery, Kansai Rosai Hospital, Hyogo.
S
S
Tamura
Department of Gastroenterological Surgery, Nippon Telegraph and Telephone Public Corporation West Osaka Hospital, Osaka.
Y
Y
Kimura
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka.
H
H
Miyata
Department of Surgery, Osaka General Medical Center, Osaka.
M
M
Motoori
Department of Surgery, Kinki University School of Medicine, Osaka Sayama, Osaka.
O
O
Shiraishi
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka.
T
T
Makino
Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
T
T
Satoh
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka.
M
M
Mori
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka.
Y
Y
Doki
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil
esophageal squamous cell carcinoma; neoadjuvant chemotherapy; phase II study