Phase II study of temozolomide monotherapy in patients with extrapulmonary neuroendocrine carcinoma

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/m2 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. EPNEC: Extrapulmonary neuroendocrine carcinoma; TMZ: Temozolomide; NENs: Neuroendocrine neoplasms.