Phase I-II study of the combination of NED, ADM, and 5-FU for the treatment of previously untreated advanced esophageal cancer

Abstract

4149 Background: Esophageal cancer has a poor prognosis. Several strategies including chemotherapy (CDDP+5-FU), either alone or with radiotherapy, depends on document reviewhave been used to improve prognosis. However, since CDDP itself has substantial toxicities, including renal and gastrointestinal toxicities, newer platinum analogues, such as nedaplatin (NED), have been developed, and it is of interest to test this new platinum analogue in a combination chemotherapy. Methods: We conducted a phase I-II study of the combination of NED (3 levels, 60–80 mg/m2 on day 1), ADM (30 mg/m2 on day 1), and 5-FU (700 mg/m2 on day 1–5) for treatment of previously untreated advanced esophageal squamous cell carcinoma. Cycles were repeated every 28 days. Objectives were to determine dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), recommended dose (RD) for a phase II study, and to explore antitumor effect. Results: Phase I: 12 patients (pts) (male/female=11/1) were evaluable. Median age 65 (range 46–74), PS 0/1=7/5. At level 1, 1 pt developed DLT (grade 4, neutropenia). At level 2, 2 pts developed DLT (grade 4 neutropenia and grade 3 diarrhea). Level 2 (70 mg/m2) was determined as the MTD and the dose at level 1 (60 mg/m2) was recommended. Phase II: 13 pts (male/female= 10/3) were at RD of level 1 at the present time. Median age 65 (range 46–75), PS 0/1= 10/3. Median number of cycles on phase II study at RD was 2 (range 1–3). 10 PRs were obtained. Response rate was 69%. Median survival time (MST) is not reached at the present time. Conclusions: This combination therapy appears to be highly active and generally well tolerated for advanced esophageal cancer. No significant financial relationships to disclose.