Phase II study of thalidomide in patients with metastatic carcinoid and islet cell tumors.
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.
Varker
Kimberly A
KA
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.
Campbell
Jacqueline
J
Shah
Manisha H
MH
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*
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D010187:Pancreatic Hormones; C050836:pancreastatin; D013792:Thalidomide