Shinomiya Hirotaka, Uehara Natsumi, Fujita Takeshi, Miyawaki Daisuke, Imamura Yoshinori, Teshima Masanori, Kakigi Akinobu, Kiyota Naomi, Sasaki Ryohei, Nibu Ken-Ichi
Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Japan.
Eur Arch Otorhinolaryngol. 2022 Jun;279(6):2805-2810. doi: 10.1007/s00405-021-06974-4. Epub 2021 Jul 14.
Chemoradiotherapy with docetaxel (DOC), cisplatin (CDDP), and 5-FU (TPF-CRT) for locally advanced external auditory canal cancer (EACC) has favorable oncological and functional outcomes. To establish TPF-CRT as a standard of care for advanced EACC, we conducted this study to determine the maximum tolerated (MTD) and recommended dose (RD) of DOC in TPF-CRT for locally advanced EACC.
To determine the recommended (RD) and maximum tolerated dose (MTD) of DOC in TPF-CRT for EACC, a phase I trial was conducted using the standard "3 + 3" design for maximum dose finding. DOC was administered twice every 4 weeks, CDDP at 70 mg/m and 5-FU at 700 mg/m; patients were also receiving radiotherapy (66 Gy). Eight patients with T3 or T4 EACC were prospectively enrolled.
Two patients treated with DOC, 50 mg/m, and one out of six patients treated with DOC, 40 mg/m, had dose-limiting toxicities. Prolonged febrile neutropenia was observed in three patients. Grade 3 non-hematological toxicities were observed in only three patients. At study completion, six patients survived, five of whom were disease free.
The RD and MTD of DOC in TPF-CRT for locally advanced EACC are 40 mg/m when doses of CDDP and 5-FU are 70 mg/m and 700 mg/m, respectively.
多西他赛（DOC）、顺铂（CDDP）和5-氟尿嘧啶（5-FU）联合进行的放化疗（TPF-CRT）用于局部晚期外耳道癌（EACC）具有良好的肿瘤学和功能学疗效。为确立TPF-CRT作为晚期EACC的标准治疗方案，我们开展了本研究，以确定TPF-CRT用于局部晚期EACC时DOC的最大耐受剂量（MTD）和推荐剂量（RD）。
为确定TPF-CRT用于EACC时DOC的推荐剂量（RD）和最大耐受剂量（MTD），采用标准的“3+3”设计进行最大剂量探索的I期试验。DOC每4周给药两次，CDDP剂量为70mg/m²，5-FU剂量为700mg/m²；患者同时接受放疗（66Gy）。前瞻性纳入8例T3或T4期EACC患者。
接受50mg/m² DOC治疗的2例患者以及接受40mg/m² DOC治疗的6例患者中的1例出现剂量限制性毒性。3例患者出现持续性发热性中性粒细胞减少。仅3例患者出现3级非血液学毒性。研究结束时，6例患者存活，其中5例无疾病。
当CDDP和5-FU的剂量分别为70mg/m²和700mg/m²时，TPF-CRT用于局部晚期EACC时DOC的RD和MTD为40mg/m²。
