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Phase II study of the proteasome inhibitor bortezomib (PS-341) in patients with metastatic neuroendocrine tumors.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2004 Sep 15; Vol. 10 (18 Pt 1), pp. 6111-8. - Publication Year :
- 2004
-
Abstract
- Purpose: This phase II study was undertaken to assess objective response, toxicity, tumor marker response, and pharmacodynamics of bortezomib in patients with metastatic neuroendocrine (carcinoid and islet cell) tumors.<br />Experimental Design: A total of 16 patients with measurable metastatic carcinoid (n=12) or islet cell (n=4) tumors received i.v. bolus of single agent bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11 every 21 days. Tumor response was assessed at 12-week intervals using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. All patients were chemotherapy naïve and had Eastern Cooperative Oncology Group performance status of 0 to 1.<br />Results: No patient achieved a partial or a complete remission. The patients received total of 264 doses of therapy with a median of 15 doses per patient. Grade 4 toxicities were not observed. The most common grade 3 adverse events included peripheral sensory neuropathy (37%), diarrhea (25%), vomiting (18%), and ileus (18%). Six of 10 patients who experienced grade 2 to 3 peripheral sensory neuropathy also had grade 2 to 3 dizziness (n=2), orthostatic hypotension (n=2), syncope (n=1), ileus (n=2), or abdominal cramps (n=1). Changes in tumor marker levels did not correlate with tumor response. The mean percentage of 20S proteasome inhibition achieved in whole blood at 1 and 24 hours after bortezomib administration was 68 and 30%, respectively.<br />Conclusions: Despite achieving the surrogate biologic end point, single-agent bortezomib did not induce any objective responses in patients with metastatic carcinoid or islet cell tumors. Additional investigation is warranted to clarify the possible association of autonomic neuropathy with bortezomib.
- Subjects :
- Adult
Aged
Biomarkers, Tumor
Bortezomib
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Metastasis
Proteasome Inhibitors
Time Factors
Treatment Outcome
Antineoplastic Agents therapeutic use
Boronic Acids therapeutic use
Carcinoid Tumor drug therapy
Neuroendocrine Tumors drug therapy
Pancreatic Neoplasms drug therapy
Protease Inhibitors therapeutic use
Pyrazines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 10
- Issue :
- 18 Pt 1
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 15447997
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-04-0422