Forrer Flavio, Uusijärvi Helena, Storch Daniel, Maecke Helmut R, Mueller-Brand Jan
Institute of Nuclear Medicine, University Hospital, Basel, Switzerland.
J Nucl Med. 2005 Aug;46(8):1310-6.
Therapy with [(90)Y-DOTA(0), Tyr(3)]-octreotide (DOTATOC, where DOTA = tetraazacyclododecane tetraacetic acid and TOC = D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol)) is established for the treatment of metastatic neuroendocrine tumors. Nevertheless, many patients experience disease relapse, and further treatment may cause renal failure. Trials with (177)Lu-labeled somatostatin analogs showed less nephrotoxicity. We initiated a prospective study with (177)Lu-DOTATOC in patients with relapsed neuroendocrine tumors after (90)Y-DOTATOC treatment.
Twenty-seven patients, pretreated with (90)Y-DOTATOC, were included. The mean time between the last treatment with (90)Y-DOTATOC and (177)Lu-DOTATOC was 15.4 +/- 7.8 mo (SD). All patients were injected with 7,400 MBq of (177)Lu-DOTATOC. Restaging was performed after 8-12 wk. Hematotoxicity or renal toxicity of World Health Organization grade 1 or 2 was not an exclusion criterion.
Creatinine levels increased significantly, from 66 +/- 14 micromol/L to 100 +/- 44 micromol/L (P < 0.0001), after (90)Y-DOTATOC therapy. The mean hemoglobin level dropped from 131 +/- 14 to 117 +/- 13 g/L (P < 0.0001) after (90)Y-DOTATOC therapy. (177)Lu-DOTATOC therapy was well tolerated. No serious adverse events occurred. The mean absorbed doses were 413 +/- 159 mGy for the whole body, 3.1 +/- 1.5 Gy for the kidneys, and 61 +/- 5 mGy for the red marrow. After restaging, we found a partial remission in 2 patients, a minor response in 5 patients, stable disease in 12 patients, and progressive disease in 8 patients. Mean hemoglobin and creatinine levels did not change significantly.
(177)Lu-DOTATOC therapy in patients with relapse after (90)Y-DOTATOC treatment is feasible, safe, and efficacious. No serious adverse events occurred.
用[(90)Y-DOTA(0), Tyr(3)]-奥曲肽（DOTATOC，其中DOTA = 四氮杂环十二烷四乙酸，TOC = D-苯丙氨酸-c(半胱氨酸-酪氨酸-D-色氨酸-赖氨酸-苏氨酸-半胱氨酸)-苏氨酸(醇)）进行治疗已被确立用于转移性神经内分泌肿瘤的治疗。然而，许多患者会出现疾病复发，且进一步治疗可能导致肾衰竭。用(177)Lu标记的生长抑素类似物进行的试验显示肾毒性较小。我们启动了一项针对(90)Y-DOTATOC治疗后复发的神经内分泌肿瘤患者的(177)Lu-DOTATOC前瞻性研究。
纳入27例曾接受(90)Y-DOTATOC预处理的患者。最后一次(90)Y-DOTATOC治疗与(177)Lu-DOTATOC治疗之间的平均时间为15.4±7.8个月（标准差）。所有患者均注射7400 MBq的(177)Lu-DOTATOC。8至12周后进行重新分期。世界卫生组织1级或2级血液毒性或肾毒性并非排除标准。
(90)Y-DOTATOC治疗后，肌酐水平显著升高，从66±14微摩尔/升升至100±44微摩尔/升（P<0.0001）。(90)Y-DOTATOC治疗后，平均血红蛋白水平从131±14降至117±13克/升（P<0.0001）。(177)Lu-DOTATOC治疗耐受性良好。未发生严重不良事件。全身平均吸收剂量为413±159毫戈瑞，肾脏为3.1±1.5戈瑞，红骨髓为61±5毫戈瑞。重新分期后，我们发现2例患者部分缓解，5例患者轻微缓解效果，12例患者病情稳定，8例患者病情进展。平均血红蛋白和肌酐水平无显著变化。
(90)Y-DOTATOC治疗后复发的患者接受(177)Lu-DOTATOC治疗是可行、安全且有效的。未发生严重不良事件。
