多西他赛（TXT）与5-氟尿嘧啶（5-FU）同步放疗用于晚期食管癌患者的I期研究。

Phase I study of docetaxel (TXT) and 5-fluorouracil (5-FU) with concurrent radiotherapy in patients with advanced esophageal cancer.

作者信息

Hihara Jun, Yoshida Kazuhiro, Hamai Yoichi, Emi Manabu, Yamaguchi Yoshiyuki, Wadasaki Koichi

机构信息

Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

出版信息

Anticancer Res. 2007 Jul-Aug;27(4C):2597-603.

PMID:17695421

Abstract

UNLABELLED

This phase I study was designed to determine the maximum-tolerated dose (MTD) of docetaxel (TXT) and toxicities of combining weekly administration of TXT and continuous infusion of 5-fluorouracil (5-FU) with concomitant radiotherapy for advanced esophageal cancer.

PATIENTS AND METHODS

Patients received TXT by i.v. infusion over 1 h on days 1, 8, 22 and 29. They were also given 5-FU 250 mg/m2/day by continuous infusion for 24 h on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45. Fractionated radiotherapy was performed on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40 and 43-45, and a total dose of 60 to 66 Gy was delivered. The starting dose level (Level 1) of TXT was set at 7.5 mg/m2. Dose escalation was conducted in increments of 25 mg/m2, until the dose reached Level 4 (15 mg/m2). At least three patients were enrolled at each level.

RESULTS

Seven patients (median age, 64 years) were enrolled. Six patients had stage III (T4NIMO) and one had stage IVb (T4N1M1b) esophageal cancer; six had squamous cell carcinoma and one had carcinosarcoma. No patient had received prior chemotherapy or radiotherapy, and two patients had undergone esophageal bypass surgery using a whole stomach tube without resection of primary or metastatic lesions. In the 7patients, the regimen was well-tolerated, with esophagitis as the most common toxicity (grade 3: n=1; grade 4: n=3). In general, hematological toxicity was mild. Dose-limiting toxicity (DLT) was observed at Level 2 (TXT 10 mg/m2) when three patients developed grade 4 esophagitis and this dose was deemed the MTD for this regimen. In the 7 assessable patients, the overall clinical response rate was 85.7%.

CONCLUSION

The MTD of TXT in this regimen was 10 mg/m2 and the recommended dose of TXT was 7.5 mg/m2. Although esophagitis was the dose-limiting and the most frequent toxicity, the regimen was safe and well-tolerated, and demonstrated the possibility of good efficacy in patients with advanced esophageal cancer.

摘要

未标记

本I期研究旨在确定多西他赛（TXT）的最大耐受剂量（MTD），以及每周给予TXT联合持续输注5-氟尿嘧啶（5-FU）并同步放疗治疗晚期食管癌的毒性。

患者与方法

患者于第1、8、22和29天静脉输注TXT 1小时。在第1 - 5、8 - 12、15 - 19、22 - 26、29 - 33、36 - 40和43 - 45天，他们还接受持续24小时的5-FU 250 mg/m²/天的输注。在第1 - 5、8 - 12、15 - 19、22 - 26、29 - 33、36 - 40和43 - 45天进行分割放疗，总剂量为60至66 Gy。TXT的起始剂量水平（1级）设定为7.5 mg/m²。剂量递增以25 mg/m²的增量进行，直至剂量达到4级（15 mg/m²）。每个剂量水平至少入组3例患者。

结果

入组7例患者（中位年龄64岁）。6例患者为III期（T4NIMO），1例为IVb期（T4N1M1b）食管癌；6例为鳞状细胞癌，1例为癌肉瘤。所有患者均未接受过先前的化疗或放疗，2例患者使用全胃管进行了食管旁路手术，未切除原发或转移病灶。在这7例患者中，该方案耐受性良好，食管炎是最常见的毒性（3级：n = 1；4级：n = 3）。总体而言，血液学毒性较轻。在2级（TXT 10 mg/m²）时观察到剂量限制性毒性（DLT），当时3例患者出现4级食管炎，该剂量被认为是该方案的MTD。在7例可评估患者中，总体临床缓解率为85.7%。