Phase I trial of 5-FU, docetaxel, and nedaplatin (UDON) combination therapy for recurrent or metastatic esophageal cancer

• Published in: Cancer chemotherapy and pharmacology Vol. 76; no. 2; pp. 279 - 285
• Main Authors: Ueda, Shinya, Kawakami, Hisato, Nishina, Shinichi, Sakiyama, Tsutomu, Nonagase, Yoshikane, Okabe, Takafumi, Tamura, Takao, Nakagawa, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2015; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - pathology; Female; Fluorouracil - administration & dosage; Humans; Male; Maximum Tolerated Dose; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oncology; Organoplatinum Compounds - administration & dosage; Original Article; Pharmacology/Toxicology; Taxoids - administration & dosage; Young Adult; Triple combination therapy; Esophageal cancer
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-015-2799-3

Purpose The aims of this dose-escalating phase I study were to determine the maximum tolerable dose (MTD) and recommended dose (RD) of 5-fluorouracil (5-FU), docetaxel, and nedaplatin (UDON) combination therapy for future phase II studies, and to evaluate the safety and efficacy of this regimen in patients with untreated recurrent or metastatic esophageal cancer. Methods Patients were administered 5-FU on days 1–5, docetaxel on days 1 and 15, and nedaplatin on day 1 at 4-week intervals. The dose levels of 5-FU/docetaxel/nedaplatin were escalated as follows (mg/m 2 ): level 1, 800/30/80; level 2, 800/30/90; and level 3, 800/35/90. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4.0. Results Overall, nine patients were enrolled in this study. All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 and were diagnosed with squamous cell carcinoma. No dose-limiting toxicity was observed at any level, and planned dose escalation was completed without reaching the MTD. No grade 4 or higher toxicity was observed in this study. The observed grade 3 hematological toxicities included neutropenia in five patients (55.6 %) and leukopenia in three patients (33.3 %). None of the patients developed febrile neutropenia, and no grade 3 or 4 non-hematological toxicities were observed. The overall response rate was 77.8 %, including two complete responses, and the disease control rate was 100 %. Conclusion The RD of UDON was identified as level 3. The good tolerability and high antitumor efficacy of this regimen warrant further evaluation in this setting.