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/m2 [dose level (DL)1] or 40 mg/m2 [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m2 cisplatin, day 1; 800 mg/m2 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.

Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan

“…13) In Japan, the JCOG conducted sequential clinical trials to improve the survival for patients with ESCC ( Table 1). 2,12,[14][15][16][17][18][19][20][21][22][23][24] The survival benefit of adjuvant chemotherapy in cStage II/III ESCC was investigated in the JCOG8503 study, where adjuvant radiotherapy (50 Gy) was compared with adjuvant chemotherapy consisting of cisplatin (CDDP) and vindesin (VDS). 15) The five year overall survival rate was 44% in the adjuvant radiotherapy group and 42% in the adjuvant chemotherapy group, indicating no difference in overall survival.…”

A randomized controlled Phase III trial comparing 2-weekly docetaxel combined with cisplatin plus fluorouracil (2-weekly DCF) with cisplatin plus fluorouracil (CF) in patients with metastatic or recurrent esophageal cancer: rationale, design and methods of Japan Clinical Oncology Group study JCOG1314 (MIRACLE study)

“…patient background) into account. The number of metastatic sites is also included because it was indicated as a prognostic factor in the previous Phase I/II trial of this study (JCOG0807) (20). .…”

“…We, JEOG, have developed a 2-weekly DCF regimen in which docetaxel is administered twice every 4 weeks (Days 1 and 15). We conducted a Phase I/II trial to determine the recommended dose for Phase II (RDP2) in Phase I and to investigate the safety and efficacy of the 2-weekly DCF regimen for metastatic or recurrent esophageal cancer (JCOG0807) treatment (20). Our study showed that the RDP2 of docetaxel was 30 mg/m , Days 1-5; every 4 weeks) had promising efficacy with a response rate of 62% and a median OS of 11.1 months.…”

Phase I/II Trial of Chemotherapy with Docetaxel, Cisplatin, and S-1 for Unresectable Advanced Squamous Cell Carcinoma of the Esophagus

“…Triplet regimens that add docetaxel to CF (DCF) are reportedly effective in patients with metastatic SCCE [9-14]. In our previous phase II trial of 48 patients with metastatic SCCE, the response rate of a DCF regimen was 62.5%.…”