O'Toole Dermot, Hentic Olivia, Corcos Olivier, Ruszniewski Philippe
Service de Gastroentérologie, Hôpital Beaujon, Clichy, France.
Neuroendocrinology. 2004;80 Suppl 1:79-84. doi: 10.1159/000080747.
Despite similar histological and morphological aspects, gastro-enteropancreatic (GEP) endocrine tumours represent a heterogeneous group of tumours with varying clinical expression depending on tumour type (functional or not), origin and extension, but also on histological differentiation and proliferative capacity. The natural history of well-differentiated tumours is often favourable without treatment and GEP endocrine tumours may remain indolent for many years. Chemotherapy may however be indicated in the presence of symptomatic non-progressive disease (progression evaluated over 3-6 months). In contrast, poorly differentiated GEP endocrine tumours are frequently aggressive and early treatment is required. Accurate staging is mandatory and where surgery is possible (even in the event of limited metastatic disease), this option should be re-evaluated in a multidisciplinary approach. Approximately 2/3 of malignant GEP tumours are metastatic at discovery and surgery is possible in a minority of patients; therefore, chemotherapy, with/without other strategies (e.g. local ablation), is frequently indicated in patients with symptomatic, bulky or progressive disease. For well-differentiated pancreatic tumours, the reference association is Adriamycin with streptozotocin yielding objective responses (OR) in 40-60% of patients. Prolonged treatment is limited due to potential cardiotoxicity of Adriamycin and standard 2nd-line regimens are not of proven efficacy; thus, other treatment modalities are usually additionally required (e.g. chemo-embolisation). A significant OR may render a small number of patients secondarily amenable to surgery. Published series evaluating chemotherapy for midgut endocrine tumours are outdated and disappointing. Objective response rates with combined associations (including either 5-fluorouracil and/or streptozotocin) rarely exceed 20% and where possible, chemo-embolisation for hepatic metastases combined with somatostatin analogues (+/- interferon) should be preferred. Poorly differentiated GEP tumours are generally aggressive tumours with metastases at diagnosis and tend to progress rapidly. Surgery is rarely possible and ineffective even in locally advanced disease due to a high risk of recurrence. Chemotherapy, using cisplatin and etoposide, is the reference treatment and frequently yields OR rates >50%. However, despite being chemosensitive, disease control is limited (8-10 months). Overall, advances in therapeutic chemotherapeutic options are required in the management of all types of advanced GEP endocrine tumours and evaluation of new drugs (e.g. irinotecan) and combination strategies (chemotherapy with local ablative therapies) are required in the future.
尽管胃肠胰(GEP)内分泌肿瘤在组织学和形态学方面相似,但它们是一组异质性肿瘤,其临床表型各异,这取决于肿瘤类型(功能性或非功能性)、起源和范围,还取决于组织学分化和增殖能力。高分化肿瘤的自然病程通常良好,无需治疗,GEP内分泌肿瘤可能多年保持惰性。然而,对于有症状的非进展性疾病(在3 - 6个月内评估进展情况),可能需要进行化疗。相反,低分化GEP内分泌肿瘤通常具有侵袭性,需要早期治疗。准确分期至关重要,若有可能进行手术(即使是有限转移性疾病的情况),应以多学科方法重新评估该选项。大约2/3的恶性GEP肿瘤在发现时已有转移,少数患者可行手术;因此,对于有症状、肿块大或病情进展的患者,常需化疗,并可联合/不联合其他策略(如局部消融)。对于高分化胰腺肿瘤,参考联合用药是阿霉素与链脲佐菌素,40 - 60%的患者会产生客观缓解(OR)。由于阿霉素潜在的心脏毒性,延长治疗受限,且标准二线方案疗效未经证实;因此,通常还需要其他治疗方式(如化疗栓塞)。显著的OR可能使少数患者随后适合手术。评估中肠内分泌肿瘤化疗的已发表系列研究过时且令人失望。联合用药(包括5 - 氟尿嘧啶和/或链脲佐菌素)的客观缓解率很少超过20%,若有可能,肝转移的化疗栓塞联合生长抑素类似物(±干扰素)应作为首选。低分化GEP肿瘤通常是侵袭性肿瘤,诊断时已有转移,且往往进展迅速。手术很少可行,即使在局部晚期疾病中也无效,因为复发风险高。使用顺铂和依托泊苷的化疗是参考治疗方法,常产生>50%的OR率。然而,尽管对化疗敏感,但疾病控制有限(8 - 10个月)。总体而言,在所有类型的晚期GEP内分泌肿瘤的管理中,化疗治疗选择需要取得进展,未来需要评估新药(如伊立替康)和联合策略(化疗与局部消融治疗联合)。