Altimari A F, Badrinath K, Reisel H J, Prinz R A
Research Service, Hines Veterans Administration Hospital, Maywood, Ill.
Surgery. 1987 Dec;102(6):1009-17.
Malignant intra-abdominal neuroendocrine tumors are rare; consequently, a standard chemotherapeutic protocol for patients with unresectable disease has not been established. This prompted a review of our experience with dimethyltriazeno imidazole carboxamide (dacarbazine) (DTIC) treatment for these tumors. From 1976 to 1986, 14 patients were treated with DTIC for metastatic neuroendocrine tumors. There were seven men and seven women whose ages ranged from 19 to 76 years. Diagnoses included eight nonfunctioning islet-cell carcinomas, three retroperitoneal neuroendocrine tumors, two glucagonomas, and one ileal carcinoid. Before DTIC chemotherapy, four patients were treated with streptozotocin and 5-FU, and one was treated with cytoxan and methotrexate without response. Two patients who were initially treated with DTIC with no response were subsequently treated with streptozotocin and 5-FU without benefit. Standard treatment with DTIC consisted of monthly cycles of 250 mg/m2/day administered intravenously for 5 days. Seven patients had an objective response to DTIC with both improvement in quality of life and a decrease of more than 50% in tumor size on computerized tomography (CT) or liver scanning. Response duration ranged from 1 to 10 years. One patient with a glucagonoma was treated for two years and had no evidence of disease at laparotomy 7 years later. Four patients with nonfunctioning islet cell carcinoma had a positive response to DTIC, but three of these patients had tumor recurrence 3 to 6 years after treatment. Two patients with retroperitoneal neuroendocrine tumors had a positive response to DTIC treatment. One patient with a glucagonoma and one with a nonfunctioning islet-cell tumor had equivocal responses with transient clinical improvement but no objective changes in tumor size. Five patients did not respond; two were given DTIC therapy as a last resort and died 1 and 12 days later. Of the other three patients, two died 6 months and one 2 years after treatment. DTIC chemotherapy was effective in 50% of patients with intra-abdominal neuroendocrine tumors. Although DTIC therapy was associated with nausea, no major gastrointestinal, hematologic, or renal complications were noted. This favorable experience with DTIC chemotherapy for nonresectable intra-abdominal neuroendocrine tumors indicates that further clinical evaluation and use are warranted.
恶性腹腔内神经内分泌肿瘤较为罕见；因此，尚未确立针对无法切除的此类疾病患者的标准化化疗方案。这促使我们回顾使用达卡巴嗪（DTIC）治疗这些肿瘤的经验。1976年至1986年，14例转移性神经内分泌肿瘤患者接受了DTIC治疗。其中男性7例，女性7例，年龄在19岁至76岁之间。诊断包括8例无功能性胰岛细胞瘤、3例腹膜后神经内分泌肿瘤、2例胰高血糖素瘤和1例回肠类癌。在接受DTIC化疗之前，4例患者接受过链脲霉素和5-氟尿嘧啶治疗，1例接受过环磷酰胺和甲氨蝶呤治疗，但均无反应。2例最初接受DTIC治疗无反应的患者随后接受链脲霉素和5-氟尿嘧啶治疗，仍无获益。DTIC的标准治疗方案为每月1个周期，静脉注射250mg/m²/天，共5天。7例患者对DTIC有客观反应，生活质量改善，计算机断层扫描（CT）或肝脏扫描显示肿瘤大小缩小超过50%。反应持续时间为1至10年。1例胰高血糖素瘤患者接受治疗2年，7年后剖腹探查未发现疾病迹象。4例无功能性胰岛细胞瘤患者对DTIC有阳性反应，但其中3例在治疗后3至6年出现肿瘤复发。2例腹膜后神经内分泌肿瘤患者对DTIC治疗有阳性反应。1例胰高血糖素瘤患者和1例无功能性胰岛细胞瘤患者反应不明确，临床有短暂改善，但肿瘤大小无客观变化。5例患者无反应；2例作为最后手段接受DTIC治疗，分别于1天和12天后死亡。另外3例患者中，2例在治疗后6个月死亡，1例在治疗后2年死亡。DTIC化疗对50%的腹腔内神经内分泌肿瘤患者有效。尽管DTIC治疗会引起恶心，但未观察到严重的胃肠道、血液学或肾脏并发症。DTIC化疗对无法切除的腹腔内神经内分泌肿瘤的良好经验表明，有必要进行进一步的临床评估和应用。
