Therapeutic options for metastatic poorly differentiated extrapulmonary neuroendocrine carcinoma (EPNEC) after prior platinum-based chemotherapy are limited. Combination chemotherapy protocols with cyclophosphamide, vincristine and either doxorubicin/adriamycin (CAV) or epirubicin (CEV) are possible treatment options for small cell lung cancer (SCLC), however have not been systematically evaluated in EPNEC so far. The aim of this study was to analyze the efficacy and toxicity of CAV/CEV in metastatic EPNEC patients.
We reviewed the combined prospective and retrospective NEN database of our center for patients treated with CAV or CEV between January 2009 and January 2019. Histological findings of all patients were reevaluated by the investigators in order to comply with the most current WHO classification.
A total of 22 patients could be identified, 19 received CAV, 3 CEV. Patients had been treated with a median of 1 line of prior chemotherapy. Median proliferation rate (Ki67) was 70 %, small cell histology was present in 63.6 % of cases. Primaries were gastrointestinal (27.3 %), pancreatobiliary (22.7%), urogenital (22.7 %), head/neck (9.1 %) or unknown (18.2 %). Best response to CAV/CEV was stable disease in 3 patients, partial remission (PR) in 5, resulting in an overall response rate of 22.7 % and disease control rate of 36.4 %. Most notably, PR was observed in both 2 patients included with a prostatic primary. Of the remaining 14 patients, 12 (54.5 %) showed a progressive disease, 1 showed a mixed response and 1 was not evaluable for response. Median progression free (PFS) and overall survival (OS) after start of CAV/CEV was 2.0 and 10.0 months respectively. Significant toxicity (mainly hematotoxicity) was observed in 63.6 % of patients.
In this first analysis of CAV/CEV in EPNEC so far, moderate antitumor activity could be detected, most notably in patients with a prostatic primary. Despite some encouraging responses, PFS was limited and significant toxicities were observed in the majority of patients.
Clinical trial identification
The trial was approved by the institutional research ethics committee (approval S-428/2014).
Legal entity responsible for the study
National Center for Tumor Diseases (NCT) Heidelberg.
Has not received any funding.
All authors have declared no conflicts of interest.