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Etoposid (VP 16-213)

Etoposide (VP 16-213) — a podophyllotoxinderivative with high antitumor activity

Eine antineoplastische Substanz aus der Reihe der Podophyllotoxine

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Summary

Etoposide is a semisynthetic podophyllotoxin derivative with a broad spectrum of antitumor activity and a relatively high therapeutic index. The synergism in animal withcis-platinum, cyclophosphamide, BCNU, and cytosinarabinoside is interesting for combination regimen. Mechanisms of action are inhibition of nucleoside transfer and of DNA and RNA synthesis, single stranded breaks, inhibition of protein synthesis and of microtubular assembly. While in lower concentrations etoposide is acting cell-cycle-dependent with accumulation of cells in the G2-phase it has, in high concentrations, also a cellcycle-phase-unspecific lethal effect.

Most suitable is the oral and i.v. application of etoposide in fractionated doses of 80–120 mg/m2 on 3–5 consecutive days and repetition after 21 [14–28] days. Side effects are dose-limiting bone marrow toxicity, nausea, vomiting, fever, hypotension, phlebitis, mucositis, neuropathy, cardiotoxicity, alopecia. Etoposide is one of the most active single agents in small-cell bronchus carcinoma with a remission rate of 37% (10% CR), and is very active in NHL (36%), testicular carcinoma (37%), AMML (35%), choriocarcinoma (35%), and neuroblastoma (29%). The role of etoposide in combination with other active drugs in these tumors is currently investigated in bronchus and testicular carcinoma and NHL, where etoposide will belong to the drugs of the first choice in the future.

Zusammenfassung

Etoposid ist ein halbsynthetisches Podophyllotoxinderivat mit einem breiten zytostatischen Wirkungsspektrum und relativ günstigem therapeutischen Index. Tierexperimentell zeigt diese Substanz einen Synergismus mitCis-Platin, Cyclophosphamid, BCNU und Cytosinarabinosid. Die Wirkmechanismen sind Hemmung des Nukleosidtransports in die Zelle, Störung der DNA- und RNA-Synthese, Einzelstrangbrüche, Störung der Proteinsynthese und Hemmung mikrotubulärer Proteine. In niedriger Konzentration wirkt Etoposid zellzyklusphasenspezifisch mit Akkumulation in der G2-Phase, in höherer Konzentration auch phasenunspezifisch. Am geeignetsten unter dem Aspekt von Wirkung und Toxizität ist die intravenöse oder orale Applikation in fraktionierten Dosen von 80–120 mg/m2 an 3–5 aufeinanderfolgenden Tagen und Wiederholung nach 21 [14–28] Tagen. Neben der dosislimitierenden Knochenmarkstoxizität sind weitere Nebenwirkungen Übelkeit, Erbrechen, Fieber, Kopfschmerz, Hypotension, Phlebitis, Mukositis, Neuropathie, Kardiotoxizität, Alopezie. Etoposid gehört zu den wirksamsten Substanzen beim kleinzelligen Bronchuskarzinom mit einer Ansprechrate von 37% (10% CR) und hat eine hohe Aktivität beim NHL (36%), Hodenkarzinom (37%), Chorion Karzinom der Frau (35%), beim Neuroblastom (29%) und bei der AMML (35%). Die Aktivität von Etoposid in Kombination mit anderen aktiven Substanzen bei diesen Tumoren wird in zur Zeit laufenden Studien untersucht; beim kleinzelligen Bronchuskarzinom sowie beim testikulären Karzinom und Non-Hodgkin-Lymphom wird Etoposid in Zukunft zu den Substanzen der ersten Wahl gehören können.

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Authors and Affiliations

  1. Abteilung Hämatologie/Onkologie des Department Innere Medizin der Medizinischen Hochschule Hannover, Germany

    H. J. Schmoll

  2. Innere Universitätsklinik und Poliklinik (Tumorforschung) des Westdeutschen Tumorzentrums Essen, Germany

    N. Niederle

  3. Abteilung Klinische Forschung/Zytostatika, Bristol Myers GmbH, Neu-Isenburg

    W. Achterrath

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  1. H. J. Schmoll
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  3. W. Achterrath
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Herrn Prof. Dr. Fritz Hartmann zum 60. Geburtstag gewidmet

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Schmoll, H.J., Niederle, N. & Achterrath, W. Etoposid (VP 16-213). Klin Wochenschr 59, 1177–1188 (1981). https://doi.org/10.1007/BF01721212

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