Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
J Nucl Med. 2010 Mar;51(3):383-90. doi: 10.2967/jnumed.109.068957. Epub 2010 Feb 11.
Regular therapy with the radiolabeled somatostatin analog (177)Lu-octreotate (22.2-29.6 GBq) in patients with gastroenteropancreatic or bronchial neuroendocrine tumors results in tumor remission in 46% of patients, including minor response. We present the effects of additional therapy with (177)Lu-octreotate in patients in whom progressive disease developed after an initial benefit from regular therapy.
Thirty-three patients with progressive disease after an initial radiologic or clinical response were treated with additional cycles of (177)Lu-octreotate. The intended cumulative dose of additional therapy was 14.8 GBq in 2 cycles. Responses were evaluated using Southwest Oncology Group criteria, including minor response (tumor size reduction of >or=25% and <50%).
Median time to progression (TTP) after regular therapy was 27 mo. In 4 patients, the intended cumulative dose was not achieved (2 had progressive disease, 2 had long-lasting thrombocytopenia). Hematologic toxicity grade 3 was observed in 4 patients, and grade 4, in 1. The median follow-up time was 16 mo (range, 1-40 mo). No kidney failure or myelodysplastic syndrome was observed. Renewed tumor regression was observed in 8 patients (2 partial remission, 6 minor response), and 8 patients had stable disease. Median TTP was 17 mo. Treatment outcome was less favorable in patients with a short TTP after regular cycles. Treatment effects in patients with pancreatic neuroendocrine tumors were similar to those in patients with other gastroenteropancreatic neuroendocrine tumors.
Most patients tolerated additional cycles with (177)Lu-octreotate well. None developed serious delayed adverse events. Additional cycles with (177)Lu-octreotate can have antitumor effects, but effects were less than for the regular cycles. This may be because of a worse clinical condition, more extensive tumor burden, or changed tumor characteristics. We conclude that this salvage therapy can be effective and is safe.
常规治疗使用放射性标记生长抑素类似物(177)Lu-奥曲肽(22.2-29.6GBq)可使胃肠胰或支气管神经内分泌肿瘤患者的肿瘤缓解率达到 46%,包括部分缓解。我们介绍了在常规治疗后出现疾病进展的患者中,使用(177)Lu-奥曲肽进行额外治疗的效果。
33 例经初始放射或临床反应后疾病进展的患者接受了额外周期的(177)Lu-奥曲肽治疗。额外治疗的预期累积剂量为 2 个周期的 14.8GBq。采用西南肿瘤协作组标准评估反应,包括部分缓解(肿瘤大小缩小≥25%但<50%)。
常规治疗后进展时间(TTP)的中位数为 27 个月。4 例患者未达到预期的累积剂量(2 例出现疾病进展,2 例出现持续血小板减少)。4 例患者出现 3 级血液学毒性,1 例出现 4 级毒性。中位随访时间为 16 个月(范围,1-40 个月)。未观察到肾衰竭或骨髓增生异常综合征。8 例患者出现肿瘤再次消退(2 例部分缓解,6 例部分缓解),8 例患者病情稳定。中位 TTP 为 17 个月。常规周期后 TTP 较短的患者治疗效果较差。胰腺神经内分泌肿瘤患者的治疗效果与其他胃肠胰神经内分泌肿瘤患者相似。
大多数患者能耐受额外周期的(177)Lu-奥曲肽治疗,无严重延迟不良反应。额外周期的(177)Lu-奥曲肽治疗具有抗肿瘤作用,但效果不如常规周期。这可能是因为患者的临床状况较差,肿瘤负荷较大,或肿瘤特征发生变化。我们的结论是,这种挽救性治疗是有效的,也是安全的。