Varker Kimberly A, Campbell Jacqueline, Shah Manisha H
Division of Hematology-Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, A438 Starling-Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA.
Cancer Chemother Pharmacol. 2008 Apr;61(4):661-8. doi: 10.1007/s00280-007-0521-9. Epub 2007 Jun 23.
Carcinoid and islet cell tumors are known to be highly vascular. There is no effective systemic therapy currently available for metastatic disease. We conducted a phase II trial to evaluate the efficacy of the anti-antiangiogenic agent thalidomide in metastatic neuroendocrine tumors.
Eighteen patients with measurable, histologically proven metastatic carcinoid neuroendocrine carcinomas (well-differentiated, n = 13; moderately-differentiated, n = 5) were enrolled on this study. The majority of the patients had gastrointestinal primaries (small bowel, 8; pancreas, 5; colon, 1). All but one patient had hepatic metastases, and 12 patients (67%) had carcinoid syndrome. All patients had Eastern Cooperative Oncology Group performance status of zero or one. Eight patients (44%) had received previous hepatic artery chemoembolization and 11 (61%) had undergone surgical resection. Patients were started on oral thalidomide at a daily dose of 200 mg that was escalated to the target dose of 400 mg daily after 2 weeks. Tumor response was assessed at 12-week intervals using RECIST criteria. Planned treatment duration was 24 weeks unless unacceptable toxicity or disease progression was observed.
No patient achieved a partial remission or a complete remission. Best response was stable disease (SD) in 11 of 16 response-evaluable patients (69%). Serum pancreastatin results did not correlate with clinical response. Grade 3 toxicities included dizziness with orthostatic hypotension (n = 5), sensory neuropathy (n = 2), fatigue (n = 2), hemorrhagic cystitis (n = 1), and deep venous thrombosis (n = 1). Frequent Grade 1-2 toxicities were: fatigue (n = 13), constipation (n = 13), dry mouth (n = 12), somnolence (n = 12), dizziness/syncope (n = 10), weight gain (n = 5), and peripheral neuropathy (n = 5).
Thalidomide was fairly well tolerated in patients with metastatic carcinoid/islet cell tumors, but failed to reveal any objective responses. The single stage design of the trial makes it difficult to determine whether observed SD in a subset of patients was attributable to the indolent nature of these tumors, or to beneficial effect of thalidomide.
已知类癌和胰岛细胞瘤血管高度丰富。目前对于转移性疾病尚无有效的全身治疗方法。我们开展了一项II期试验，以评估抗血管生成药物沙利度胺对转移性神经内分泌肿瘤的疗效。
18例经组织学证实有可测量转移灶的类癌神经内分泌癌患者（高分化，n = 13；中分化，n = 5）入组本研究。大多数患者的原发肿瘤位于胃肠道（小肠，8例；胰腺，5例；结肠，1例）。除1例患者外，所有患者均有肝转移，12例患者（67%）有类癌综合征。所有患者东部肿瘤协作组体能状态均为0或1。8例患者（44%）曾接受过肝动脉化疗栓塞，11例患者（61%）接受过手术切除。患者开始口服沙利度胺，每日剂量200 mg，2周后增至目标剂量每日400 mg。每12周根据RECIST标准评估肿瘤反应。计划治疗周期为24周，除非观察到不可接受的毒性或疾病进展。
无患者达到部分缓解或完全缓解。16例可评估反应的患者中，11例（69%）的最佳反应为疾病稳定（SD）。血清胰抑制素结果与临床反应无关。3级毒性反应包括伴体位性低血压的头晕（n = 5）、感觉神经病变（n = 2）、疲劳（n = 2）、出血性膀胱炎（n = 1）和深静脉血栓形成（n = 1）。常见的1 - 2级毒性反应有：疲劳（n = 13）、便秘（n = 13）、口干（n = 12）、嗜睡（n = 12）、头晕/晕厥（n = 10）、体重增加（n = 5）和周围神经病变（n = 5）。
沙利度胺在转移性类癌/胰岛细胞瘤患者中耐受性较好，但未显示出任何客观反应。该试验的单阶段设计使得难以确定在部分患者中观察到的疾病稳定是归因于这些肿瘤的惰性本质，还是沙利度胺的有益作用。
