EpiCO (epirubicin, cyclophosphamide and vincristine) as treatment for extrapulmonary high-grade neuroendocrine neoplasms

Abstract

High-grade neuroendocrine neoplasms (NEN) comprise a rare entity. Due to the lack of randomized controlled trials, therapy recommendations were mainly extrapolated from its pulmonary analogue, small cell lung cancer and mostly validated in small retrospective case series. The multicentric Nordic NEC Study of gastro-entero-pancreatic (GEP) and cancer of unknown primary (CUP) high-grade neuroendocrine neoplasms showed a significant disease control upon treatment with etoposide and platinum-based chemotherapies [1]. Such a combination with etoposide and a platinum (CE) compound is currently considered standard first-line treatment for high-grade GEP/CUP NEN. High-grade mixed-neuroendocrine-non-neuroendocrine neoplasms (MiNEN) formerly termed mixed adeno-neuroendocrine carcinomas (MANEC) also have a poor prognosis and are generally treated like other high-grade NEN. The CE protocol has significant activity in high-grade NEN and MiNEN, but the response is short-lived in most cases with response rates around 50–60 %. Second-line treatment alternatives are not established so far. The need for additional treatment options is evident.

Combination chemotherapy with doxorubicin, cyclophosphamide and vincristine (CAV) showed efficacy in small cell lung carcinoma (SCLC) and was considered standard first-line therapy before the era of etoposide and platinum combinations. Due to a better toxicity profile, doxorubicin was replaced by epirubicin, resulting in the combination of epirubicin, cyclophosphamide and vincristine (abbreviated as EpiCO or CEV).

In analogy to SCLC, selected patients with high-grade NEN were treated with the EpiCO regimen in second line (or in one patient first line) at our center. In this report we present the retrospective series of 5 cases with metastatic high-grade GEP/CUP NEN/MiNEN who received chemotherapy according to this protocol.

Zusammenfasung

High-grade neuroendokrine Neoplasien (NEN) sind eine seltene Entität. Bisher sind keine randomisierten kontrollierten Studien durchgeführt worden. Therapieempfehlungen sind hauptsächlich von dem pulmonalen Analog, dem kleinzelligen Bronchialkarzinom (SCLC), extrapoliert und in retrospektiven Fallserien validiert. Die multizentrische Nordic-NEC-Studie von gastroenteropathischen (GEP) und „cancer of unknown primary“ (CUP) high-grade neuroendokrinen Neoplasien zeigte ein signifikantes Therapieansprechen auf etoposid- und platinhaltige Kombinationen [1]. Diese Kombination ist Standard-Erstlinientherapie für high-grade GEP/CUP NEN. High-grade gemischtzellige neuroendokrine/nicht-neuroendokrine Neoplasien (MiNEN), früher auch als gemischtzellige adenoneuroendokrine Karzinome (MANEC) bezeichnet, zeigen ebenfalls eine schlechte Prognose und werden wie andere high-grade NEN behandelt. Das Carboplatin/Etoposide(CE)-Protokoll zeigt ein Ansprechen von 50–60 % in high-grade NEN und MiNEN, aber Remissionen sind häufig von kurzer Dauer [1]. Zweitlinientherapien sind nicht allgemein etabliert.

Eine Therapie mit Doxorubicin, Cyclophosphamid und Vincristine (CAV) zeigte Effektivität beim SCLC und galt als Standardchemotherapie vor der Ära von etoposid- und platinhaltigen Zytostatikakombinationen. Aufgrund eines besseren Toxizitätsprofils wurde Doxorubicin durch Epirubicin ersetzt, das daraus resultierende Regime mit Epirubicin, Cyclophosphamid und Vincristin wurde EpiCO oder CEV abgekürzt [4] [5] [6].

In Analogie zum SCLC wurden ausgewählte Patienten mit high-grade NEN mit EpiCO in einem Zweitliniensetting am Universitätsklinikum Regensburg behandelt. In dieser retrospektiven Arbeit berichten wir von 5 Patienten mit metastasiertem high-grade GEP/CUP NEN/MiNEN, die eine Chemotherapie nach diesem Schema erhielten.

Key words

neuroendocrine neoplasms - high-grade neuroendocrine carcinoma - mixed-neuroendocrine-non-neuroendocrine neoplasm - mixed adeno-neuroendocrine carcinoma - epirubicin - cyclophosphamide - vincristine

Schlüsselwörter

neuroendokrine Neoplasien - high-grade neuroendokrines Karzinom - gemischt-neuroendokrines-nicht-neuroendokrines Karzinom - Epirubicin - Cyclophosphamid - Vincristin

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