title: Phase II study of thalidomide in patients with metastatic carcinoid and islet cell tumors.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Varker
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Campbell
authors.forename: Manisha H
authors.initials: MH
authors.lastname: Shah
mesh_terms: D007516:Adenoma, Islet Cell / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000556:secondary*; D053379:Chromogranin A; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010187:Pancreatic Hormones / Q000097:blood; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D010187:Pancreatic Hormones; C050836:pancreastatin; D013792:Thalidomide