Kudo Atsushi, Tateishi Ukihide, Yoshimura Ryoichi, Tsuchiya Junichi, Yokoyama Kota, Takano Shoko, Kobayashi Noritoshi, Utsunomiya Daisuke, Hata Masaharu, Ichikawa Yasushi, Tanabe Minoru, Hosono Makoto, Kinuya Seigo
Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Diagnostic Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
J Hepatobiliary Pancreat Sci. 2022 Apr;29(4):487-499. doi: 10.1002/jhbp.1101. Epub 2021 Dec 27.
The present prospective phase 1/2 study aimed to elucidate the efficacy and safety of Lu-DOTATATE (four cycles of 7.4 GBq) in Japanese patients with unresectable, progressive neuroendocrine tumors (NETs).
From April 2018 to October 2020, 15 patients with advanced NETs (five midgut, eight pancreatic, and two lung NETs) were enrolled. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were evaluated. Pharmacokinetics and dosimetry were also evaluated in three midgut patients.
The mean absorbed doses of Lu-DOTATATE to the kidneys (20.7 Gy/29.6 GBq) and the bone marrow (0.631 Gy/29.6 GBq) were within the radiation tolerance doses. The ORR of the whole population was 53% (90% CI, 30%-76%). ORRs of the midgut and non-midgut NETs were 60% (90% CI, 19%-92%) and 50% (90% CI, 22%-78%), respectively. There was no difference in the maximum reduction rate of the sum of the target lesion diameters between patients with midgut and non-midgut NET. The median PFS was not reached; the PFS rate at 52 weeks was 80% (90% CI, 56.1%-91.7%). AEs of Grade 3 or higher were lymphopenia (47%) and leukopenia (7%).
Lu-DOTATATE demonstrated remarkable tumor shrinkage and tolerability in Japanese patients with advanced NETs.
本前瞻性1/2期研究旨在阐明177Lu-DOTATATE（四个周期，7.4GBq）对日本不可切除、进展性神经内分泌肿瘤（NETs）患者的疗效和安全性。
2018年4月至2020年10月，纳入15例晚期NETs患者（5例中肠、8例胰腺和2例肺NETs）。评估客观缓解率（ORR）、无进展生存期（PFS）和不良事件（AE）。还对3例中肠患者进行了药代动力学和剂量学评估。
177Lu-DOTATATE对肾脏（20.7Gy/29.6GBq）和骨髓（0.631Gy/29.6GBq）的平均吸收剂量在放射耐受剂量范围内。总体人群的ORR为53%（90%CI，30%-76%）。中肠和非中肠NETs的ORR分别为60%（90%CI，19%-92%）和50%（90%CI，22%-78%）。中肠和非中肠NETs患者之间，靶病灶直径总和的最大缩小率无差异。未达到中位PFS；52周时的PFS率为80%（90%CI，56.1%-91.7%）。3级或更高等级的AE为淋巴细胞减少（47%）和白细胞减少（7%）。
177Lu-DOTATATE在日本晚期NETs患者中显示出显著的肿瘤缩小和耐受性。
