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Research article
Phase II study of temozolomide monotherapy in patients with extrapulmonary poorly differentiated neuroendocrine carcinoma that were resistant to platinum-based chemotherapy
Noritoshi Kobayashi
Yokohama City University Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9181-3722
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This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
Extraplumonary; poorly differentiated; neuroendocrine carcinoma; Temozolomide; phase II study;
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This is a preprint. It has not completed peer review.
Research article
Phase II study of temozolomide monotherapy in patients with extrapulmonary poorly differentiated neuroendocrine carcinoma that were resistant to platinum-based chemotherapy
Noritoshi Kobayashi
Yokohama City University Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9181-3722
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 22 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.