Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Guangdong Association Study of Thoracic Oncology, Guangzhou, China.
Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Radiother Oncol. 2021 Feb;155:105-112. doi: 10.1016/j.radonc.2020.10.035. Epub 2020 Nov 2.
This phase I trial aimed to determine the maximal tolerated dose (MTD) of incorporating a twice-weekly docetaxel and nedaplatin regimen into definitive concurrent chemoradiotherapy (CCRT) as radiosensitizers in patients with inoperable esophageal squamous cell carcinoma (ESCC).
The CCRT regimen included docetaxel (5 mg/m, 10 mg/m, or 15 mg/m) and nedaplatin (5 mg/m, 10 mg/m, or 15 mg/m) twice-weekly based on the traditional 3 + 3 dose escalation strategy, and radiotherapy (64 Gy in 32 fractions). The primary goals were to determine the MTD of concurrent chemotherapy and the dose limiting toxicities (DLTs). In-field objective response rate (ORR) was investigated.
Fifteen patients had been recruited and analyzed. DLT involving persistent grade 3 esophagitis over 1 week was observed in all three patients (3/3) at dose level 3 (15 mg/m), and two patients (2/6) experienced DLTs in the dose level 2 (10 mg/m) due to esophageal fistula and persistent grade 3 esophagitis over 1 week, while one patient (1/6) treated at dose level 1 (5 mg/m) exhibited DLT owing to Grade 3 increased liver enzymes, suggesting a MTD of 5 mg/m. The in-filed ORR was both 100% in all patients and those receiving MTD. The 1-year loco-regional recurrence-free survival rate was 83.3%, 83.3% and 66.7% in dose level 1, 2, and 3, respectively.
The MTD of twice-weekly docetaxel and nedaplatin regimen was 5 mg/m in inoperable ESCC patients treated with definitive CCRT. Low dose concurrent docetaxel and nedaplatin showed promising radiosensitizing effect on in-filed disease control and good tolerability.
本Ⅰ期临床试验旨在确定每周两次联合多西他赛和奈达铂方案作为不可切除食管鳞癌（ESCC）患者根治性同期放化疗（CCRT）增敏剂的最大耐受剂量（MTD）。
CCRT 方案包括每周两次多西他赛（5mg/m、10mg/m 或 15mg/m）和奈达铂（5mg/m、10mg/m 或 15mg/m），基于传统的 3+3 剂量递增策略，联合放疗（64Gy/32 次）。主要目标是确定同期化疗的 MTD 和剂量限制性毒性（DLT）。评估了靶区客观缓解率（ORR）。
共纳入并分析了 15 例患者。在剂量水平 3（15mg/m），3 例患者（3/3）出现持续 1 周以上的 3 级食管炎，所有患者均出现 DLT；2 例患者（2/6）因食管瘘和持续 1 周以上的 3 级食管炎在剂量水平 2（10mg/m）发生 DLT；1 例患者（1/6）在剂量水平 1（5mg/m）发生 DLT，因肝功能酶升高 3 级。提示 MTD 为 5mg/m。所有患者和接受 MTD 治疗的患者靶区 ORR 均为 100%。1 年局部区域无复发生存率在剂量水平 1、2 和 3 组中分别为 83.3%、83.3%和 66.7%。
每周两次多西他赛和奈达铂方案在接受根治性 CCRT 的不可切除 ESCC 患者中，MTD 为 5mg/m。低剂量同期多西他赛和奈达铂对靶区疾病控制具有良好的增敏作用和良好的耐受性。
