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长效生长抑素类似物联合抗肿瘤药物治疗小细胞肺癌患者。

Long acting somatostatin analogues in combination to antineoplastic agents in the treatment of small cell lung cancer patients.

机构信息

Lung Tumour Research Section, Pulmonary Department, Aristotle University Pulmonary Clinic, G. Papanikolaou Hospital, Exohi, Thessaloniki, Greece.

出版信息

Lung Cancer. 2012 Apr;76(1):84-8. doi: 10.1016/j.lungcan.2011.09.014. Epub 2011 Oct 22.

Abstract

BACKGROUND

Long acting somatostatin analogues combined with platinum analogues have demonstrated an antiproliferative effect on growth of human SCLC xenographs.

METHOD

130 previously untreated SCLC patients--54 with limited disease (LD) and positive somatostatin receptors were included in the study. All patients performed 111In-Octreotide scanning before chemotherapy (CHT), every 3 months and up to 4 times. All patients were treated with paclitaxel 190 mg/m2+carboplatin AUC=5.5 for up to 6 cycles. 47/130 patients (Group A, control group) received only CHT. Forty eight hours after each CHT 43/130 patients (Group B) were also administered 30 mg somatuline® (lanreotide) by a single subcutaneous (s.c.) injection to stimulate somatostatin receptors (SSTRS) for 2 weeks. 40/130 patients (Group C) received 60 mg somatuline® autogel to stimulate SSTRS for 4 weeks. Patients in Groups A and B after the completion of the CHT continued maintenance therapy with somatuline. NSE, IGF1, VEGFA, VEGFC, VEGFR2, HER2 levels were monitored. In histological samples Bcl-2 and VEGF were also explored by immunohistochemistry.

RESULTS

No statistically significant differences were observed between the 3 Groups regarding LD and extensive disease (ED) patient ratios, age and PS. Group B had a survival benefit in comparison to Groups A and C (p=0.029). LD patients of Group B had a significant benefit compared to Groups A and C (p=0.012, Breslow test). In LD Group B had a significant longer TTP (p=0.02) in comparison to Groups A and C. Adverse effects had no statistically significant difference between the Groups and toxicity was well managed.

INTERPRETATION

Long acting somatostatin analogues could be used as an additive therapy in combination to antineoplastic agents in patients positive for somatostatin receptors. A dose of 30 mg improved survival only in LD SCLC patients.

摘要

背景

长效生长抑素类似物联合铂类药物已被证明对人小细胞肺癌异种移植的生长具有抗增殖作用。

方法

本研究纳入了 130 例未经治疗的小细胞肺癌患者,其中 54 例为局限性疾病(LD)且生长抑素受体阳性。所有患者在化疗(CHT)前、每 3 个月以及最多 4 次进行 111In-Octreotide 扫描。所有患者均接受紫杉醇 190mg/m2+卡铂 AUC=5.5 治疗,最多 6 个周期。130 例患者中的 47 例(A 组,对照组)仅接受 CHT。在每次 CHT 后 48 小时,130 例患者中的 48 例(B 组)还接受了 30mg 善宁®(兰瑞肽)皮下注射,单次给药,刺激生长抑素受体(SSTRS)2 周。130 例患者中的 40 例(C 组)接受了 60mg 善宁®长效微球,以刺激 SSTRS 4 周。A 组和 B 组患者在 CHT 完成后继续接受善宁维持治疗。监测 NSE、IGF1、VEGFA、VEGFC、VEGFR2、HER2 水平。在组织学样本中,还通过免疫组化法探索了 Bcl-2 和 VEGF。

结果

在 LD 和广泛疾病(ED)患者比例、年龄和 PS 方面,3 组之间无统计学差异。与 A 组和 C 组相比,B 组的生存获益具有统计学意义(p=0.029)。与 A 组和 C 组相比,B 组 LD 患者的获益具有统计学意义(p=0.012,Breslow 检验)。在 LD 中,B 组与 A 组和 C 组相比,TTP 显著延长(p=0.02)。各组之间的不良反应无统计学差异,且毒性得到良好控制。

结论

长效生长抑素类似物可作为对生长抑素受体阳性患者的附加治疗与抗肿瘤药物联合使用。30mg 的剂量仅可改善 LD 小细胞肺癌患者的生存。

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