1. Phase II study of temozolomide monotherapy in patients with extrapulmonary neuroendocrine carcinoma.
- Author
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Kobayashi N, Takeda Y, Okubo N, Suzuki A, Tokuhisa M, Hiroshima Y, and Ichikawa Y
- Subjects
- Adult, Aged, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Neuroendocrine enzymology, Carcinoma, Neuroendocrine mortality, Carcinoma, Neuroendocrine pathology, Colonic Neoplasms drug therapy, Colonic Neoplasms enzymology, Colonic Neoplasms pathology, Drug Administration Schedule, Duodenal Neoplasms drug therapy, Duodenal Neoplasms enzymology, Duodenal Neoplasms pathology, Female, Gallbladder Neoplasms drug therapy, Gallbladder Neoplasms enzymology, Gallbladder Neoplasms pathology, Humans, Ki-67 Antigen analysis, Liver Neoplasms drug therapy, Liver Neoplasms enzymology, Liver Neoplasms pathology, Male, Middle Aged, O(6)-Methylguanine-DNA Methyltransferase analysis, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms enzymology, Pancreatic Neoplasms pathology, Progression-Free Survival, Prospective Studies, Stomach Neoplasms drug therapy, Stomach Neoplasms enzymology, Stomach Neoplasms pathology, Temozolomide administration & dosage, Temozolomide adverse effects, Uterine Neoplasms drug therapy, Uterine Neoplasms enzymology, Uterine Neoplasms pathology, Antineoplastic Agents, Alkylating therapeutic use, Carcinoma, Neuroendocrine drug therapy, Temozolomide therapeutic use
- Abstract
Extrapulmonary neuroendocrine carcinoma (EPNEC) is a lethal disease with a poor prognosis. Platinum-based chemotherapy is used as the standard first-line treatment for unresectable EPNEC. Several retrospective studies have reported the results of the utilization of temozolomide (TMZ) as a drug for the second-line treatment for EPNEC. Patients with unresectable EPNEC that were resistant to platinum-based combination chemotherapy were recruited for a prospective phase II study of TMZ monotherapy. A 200 mg/m
2 dose of TMZ was given from day 1 to day 5, every 4 weeks. Response rate (RR) was evaluated as the primary end-point. The presence of O6 -methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research. Thirteen patients were enrolled in this study. Primary lesions were pancreas (n = 3), stomach (n = 3), duodenum (n = 1), colon (n = 1), gallbladder (n = 1), liver (n = 1), uterus (n = 1), bladder (n = 1), and primary unknown (n = 1). Each case was defined as pathological poorly differentiated neuroendocrine carcinoma from surgically resected and/or biopsied specimens. The median Ki-67 labeling index was 60% (range, 22%-90%). The RR was 15.4%, progression-free survival was 1.8 months (95% confidence interval [CI], 1.0-2.7), overall survival (OS) was 7.8 months (95% CI, 6.0-9.5), and OS from first-line treatment was 19.2 months (95% CI, 15.1-23.3). No grade 3 or 4 hematological toxicity had occurred and there was one case of grade 3 nausea. One case presented MGMT deficiency and this case showed partial response. Temozolomide monotherapy is a feasible, modestly effective, and safe treatment for patients with unresectable EPNEC following platinum-based chemotherapy, especially those with MGMT deficiency., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)- Published
- 2021
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