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生长抑素类似物奥曲肽与转移性内分泌胃肠胰腺肿瘤的肿瘤生长抑制

Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours.

作者信息

Arnold R, Trautmann M E, Creutzfeldt W, Benning R, Benning M, Neuhaus C, Jürgensen R, Stein K, Schäfer H, Bruns C, Dennler H J

机构信息

Department of Internal Medicine, Philipps-University, Baldingerstrasse, Germany.

出版信息

Gut. 1996 Mar;38(3):430-8. doi: 10.1136/gut.38.3.430.

Abstract

Antiproliferative treatment of patients with metastatic endocrine gastroenteropancreatic tumours (GEP) is based mainly on chemotherapeutic protocols whereby drug toxicity is a major handicap. Octreotide is the first choice in the control of hormone mediated symptoms. From retrospective and a few prospective studies it has been suggested that octreotide exhibits antiproliferative properties. The prospective German Sandostatin multicentre phase II trial investigated the effects of 200 micrograms octreotide thrice daily for one year on tumour growth and endocrine abnormalities in 103 patients. Octreotide treatment was continued in those patients responding to the drug until tumour progression occurred. In 28 of those with tumour progression during 200 micrograms thrice daily octreotide dose was increased to 500 micrograms thrice daily. The study sample consisted of 52 patients with computed tomography confirmed tumour progression and 13 patients with stable disease before octreotide treatment, whereas no preobservation period was available in 38 patients. Nineteen patients (36.5%) with computed tomography confirmed tumour progression experienced stabilisation of tumour growth lasting for at least three months. Median duration of stable disease was 18 months. At month 12, stable disease continued in 12 patients, declined after 24 months to nine patients, and after 36 months to five patients. Tumour regression has not been seen in this or other subgroups. In the subgroup with stable disease before octreotide, stable disease continued in 53.8% of patients over 12 months. Increase of octreotide dose to 500 micrograms thrice daily did not influence progression seen during the lower dose with the exception of one patient in whom tumour progression changed to stable disease. No association of tumour size response and patients' characteristics could be detected. The results suggest that octreotide inhibits tumour growth in patients with metastasised endocrine GEP tumours. The antiproliferative effect is, at least in some patients, longlasting. Currently, octreotide can only be recommended as an antiproliferative drug if patients with clearly progressive disease show stabilisation after treatment for three to six months.

摘要

转移性内分泌胃肠胰肿瘤(GEP)患者的抗增殖治疗主要基于化疗方案,而药物毒性是一个主要障碍。奥曲肽是控制激素介导症状的首选药物。回顾性研究和一些前瞻性研究表明,奥曲肽具有抗增殖特性。德国前瞻性生长抑素多中心II期试验研究了103例患者每日三次服用200微克奥曲肽,持续一年对肿瘤生长和内分泌异常的影响。对药物有反应的患者继续接受奥曲肽治疗,直至肿瘤进展。在28例每日三次服用200微克奥曲肽期间出现肿瘤进展的患者中,剂量增加至每日三次500微克。研究样本包括52例经计算机断层扫描证实肿瘤进展的患者和13例奥曲肽治疗前病情稳定的患者,而38例患者没有观察前期。19例(36.5%)经计算机断层扫描证实肿瘤进展的患者经历了至少持续三个月的肿瘤生长稳定期。疾病稳定的中位持续时间为18个月。在第12个月时,12例患者疾病持续稳定;24个月后降至9例;36个月后降至5例。在该亚组或其他亚组中均未观察到肿瘤消退。在奥曲肽治疗前病情稳定的亚组中,53.8%的患者在12个月以上疾病持续稳定。将奥曲肽剂量增加至每日三次500微克,除1例患者肿瘤进展转变为病情稳定外,对低剂量时出现的进展没有影响。未检测到肿瘤大小反应与患者特征之间的关联。结果表明,奥曲肽可抑制转移性内分泌GEP肿瘤患者的肿瘤生长。至少在一些患者中,抗增殖作用是持久的。目前,只有当明确进展性疾病的患者在治疗三至六个月后病情稳定时,才可以推荐将奥曲肽作为抗增殖药物。

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