Phase II study of temozolomide monotherapy in patients with extrapulmonary poorly differentiated neuroendocrine carcinoma that were resistant to platinum-based chemotherapy
Background: Extrapulmonary poorly differentiated 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.
Methods: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 administered from day 1 to day 5, every four weeks. Response rate (RR) was evaluated as the primary endpoint. The presence of O6-methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research.
Results: 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 surgical resected and/or biopsied specimens. The median Ki67 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 grade 3 nausea and appetite loss had occurred one case. One case presented MGMT deficiency and this case showed partial response.
Conclusion: TMZ monotherapy is a feasible, modestly effective, and safety treatment for patients with unresectable EPNEC following platinum-based chemotherapy. MGMT deficiency may be a reliable biomarker for the response of unresectable EPNEC to TMZ.
Trial registration: Registered at April 20, 2013. Registry number: UMIN000010549.
Figure 1
Figure 2
Figure 3
Due to technical limitations the Tables are available as a download in the Supplementary Files.
This is a list of supplementary files associated with this preprint. Click to download.
Posted 22 Jun, 2020
Phase II study of temozolomide monotherapy in patients with extrapulmonary poorly differentiated neuroendocrine carcinoma that were resistant to platinum-based chemotherapy
Posted 22 Jun, 2020
Background: Extrapulmonary poorly differentiated 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.
Methods: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 administered from day 1 to day 5, every four weeks. Response rate (RR) was evaluated as the primary endpoint. The presence of O6-methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research.
Results: 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 surgical resected and/or biopsied specimens. The median Ki67 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 grade 3 nausea and appetite loss had occurred one case. One case presented MGMT deficiency and this case showed partial response.
Conclusion: TMZ monotherapy is a feasible, modestly effective, and safety treatment for patients with unresectable EPNEC following platinum-based chemotherapy. MGMT deficiency may be a reliable biomarker for the response of unresectable EPNEC to TMZ.
Trial registration: Registered at April 20, 2013. Registry number: UMIN000010549.
Figure 1
Figure 2
Figure 3
Due to technical limitations the Tables are available as a download in the Supplementary Files.