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).

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. 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. 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. 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. University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).

Yamasaki M ，Yasuda T ，Yano M ，Hirao M ，Kobayashi K ，Fujitani K ，Tamura S ，Kimura Y ，Miyata H ，Motoori M ，Shiraishi O ，Makino T ，Satoh T ，Mori M ，Doki Y ... -  《-》

Neoadjuvant Chemotherapy with Divided-dose Docetaxel, Cisplatin and Fluorouracil for Patients with Squamous Cell Carcinoma of the Esophagus.

The aim of this phase II study was to evaluate the feasibility of a neoadjuvant chemotherapy regimen consisting of divided-dose docetaxel and cisplatin, with 5-fluorouracil (NAC-DCF), for treatment of patients with stage II/III squamous cell carcinoma of the esophagus (SCCE). The NAC-DCF regimen, consisting of 2-h infusion of docetaxel at 35 mg/m(2) on days 1 and 8, 4-h infusion of cisplatin at 12 mg/m(2) on days 1-5, and continuous infusion of 5-fluorouracil at 600 mg/m(2) on days 1-5, was administered. We compared NAC-DCF with conventional NAC-CF. The DCF group comprised of 45 patients, and the CF group comprised of 28 patients. The incidence of grade 3/4 neutropenia was significantly higher in the DCF group (56%) than in the CF group (0%). Grade 2/3 pathological response was attained in a significantly higher percentage of patients in the DCF group (40%) than in the CF group (11%) (p=0.0153). This DCF regimen led to a high frequency of pathological responses among patients with advanced SCCE.

Ojima T ，Nakamori M ，Nakamura M ，Katsuda M ，Hayata K ，Kato T ，Kitadani J ，Tabata H ，Takeuchi A ，Iwahashi M ，Yamaue H ... -  《-》

Feasibility of Preoperative Chemotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil versus Adriamycin, Cisplatin, and 5-Fluorouracil for Resectable Advanced Esophageal Cancer.

Neoadjuvant chemotherapy for resectable advanced esophageal squamous cell carcinoma (ESCC) requires reassessment. We have conducted a trial aiming at the comparison between DCF and ACF concerning perioperative adverse events. Patients were randomly assigned to receive either DCF [docetaxel 70 mg/m2, cisplatin 70 mg/m2 on day 1, and 5-fluorouracil (5-FU) 700 mg/m2 for 5 days] every 3 weeks or ACF (adriamycin 35 mg/m2, cisplatin 70 mg/m2 on day 1, and 5-FU 700 mg/m2 for 7 days) every 4 weeks. Each group consisted of 81 patients. Two cycles of preoperative chemotherapy were planned, after which patients underwent subtotal esophagectomy via a right thoracotomy with lymphadenectomy. Chemotherapy- and surgery-related adverse effects were assessed. Grade 3-4 neutropenia and febrile neutropenia occurred in 90 and 39% of patients, respectively, in the DCF group compared with 69 and 17% of patients, respectively, in the ACF group (p < 0.01). Perioperative complications did not differ significantly between the groups. The overall response rates of DCF and ACF were 61 and 40%, respectively, while the histopathological complete responses were 15 and 3%, respectively (p < 0.01). The DCF and ACF regimens were found to be equally feasible in patients with resectable advanced ESCC; however, DCF delivered an antitumor effect and therefore potentially improved the long-term outcomes.

Shiraishi O ，Yamasaki M ，Makino T ，Motoori M ，Miyata H ，Shinkai M ，Kimura Y ，Hirao M ，Fujitani K ，Tamura S ，Kobayashi K ，Yano M ，Doki Y ，Yasuda T ... -  《-》

Long-term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5-fluorouracil vs docetaxel, cisplatin, and 5-fluorouracil followed by surgery for esophageal cancer (OGSG1003).

The aim is to report the long-term outcomes of preoperative cisplatin and fluorouracil plus docetaxel (DCF) vs Adriamycin (ACF) for resectable esophageal squamous cell carcinoma (ESCC). Previously, this trial showed that DCF is associated with prolonged recurrence-free survival (RFS). Patients were randomly assigned to two cycles of ACF (35 mg/m2 of Adriamycin, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 7 days) every 4 weeks or DCF (70 mg/m2 of docetaxel, 70 mg/m2 of cisplatin intravenously on day 1, and 700 mg/m2 of fluorouracil infusion for 5 days) every 3 weeks, followed by surgery. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, 162 of whom were eligible and randomly assigned to the two groups. The median follow-up for surviving patients was 69.8 months. The 5-year RFS was significantly better in the DCF group than in the ACF group (59.9% vs 40.7%, hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.35-0.86; P = .009) and the 5-year OS was significantly better in the DCF group than in the ACF group (63.5% vs 49.4%, HR, 0.61; 95% CI, 0.38-0.96; P = .03). The benefit of DCF chemotherapy on survival was significantly greater in the subgroups with more advanced clinical T and N stage. Cisplatin and fluorouracil plus docetaxel are associated with better RFS and OS than ACF in resectable ESCC patients.

Sugimura K ，Yamasaki M ，Yasuda T ，Yano M ，Hirao M ，Fujitani K ，Kimura Y ，Miyata H ，Motoori M ，Takeno A ，Shiraishi O ，Makino T ，Kii T ，Tanaka K ，Satoh T ，Mori M ，Doki Y ... -  《Annals of Gastroenterological Surgery》

Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma.

The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70-75 mg/m(2)) and cisplatin (70-75 mg/m(2)) on day 1, and continuous infusion of fluorouracil (750 mg/m(2)/day) on days 1-5. Antibiotic prophylaxis on days 5-15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty-two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty-one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment-related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2-year progression-free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396).

Hara H ，Tahara M ，Daiko H ，Kato K ，Igaki H ，Kadowaki S ，Tanaka Y ，Hamamoto Y ，Matsushita H ，Nagase M ，Hosoya Y ... -  《-》