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Phase II study of thalidomide in patients with metastatic carcinoid and islet cell tumors

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Abstract

Purpose

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.

Patients and 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.

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Acknowledgments

This work was supported by a grant from the Celgene Corporation, Summit, NJ.

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Authors and Affiliations

  1. 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

    Kimberly A. Varker, Jacqueline Campbell & Manisha H. Shah

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  1. Kimberly A. Varker
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  2. Jacqueline Campbell
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  3. Manisha H. Shah
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Correspondence to Manisha H. Shah.

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Varker, K.A., Campbell, J. & Shah, M.H. Phase II study of thalidomide in patients with metastatic carcinoid and islet cell tumors. Cancer Chemother Pharmacol 61, 661–668 (2008). https://doi.org/10.1007/s00280-007-0521-9

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  • DOI: https://doi.org/10.1007/s00280-007-0521-9

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