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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Literatur
Ahmann DL, Bisel HF, Eagan RT, Edmonson JH, Hahn RG, O'Connell MJ, Frytag S (1976) Phase II evaluation of VP 16-213 (NSC-141540) and cytembena (NSC-104801) in patients with advanced breast cancer. Cancer Treat Rep 60:633–635
Aisner J, Whitacre M, Van Echo DA, Esteray RJ, Wiernik PH (1980) Alternating non-cross resistant combination chemotherapy for small cell carcinoma of the lung (SCCL). Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:453 (ASCO Abstr. C 528)
Aisner J, Whitacre M, Van Echo DA, Wiernik PH (1980) Treatment of small cell carcinoma of the lung with alternating combination chemotherapies or sequential combinations. Second world conference on lung cancer, abstract. Excerpta Medica, Amsterdam Oxford Princeton, pp 139
Allen LM, Creaven PJ (1975) Comparison of the human pharmacokinetics of VM-26 and VP-16, two antineoplastic epipodophyllotoxin glucopyranoside derivatives. Eur J Cancer 11:697–707
Allen LM, Marcks C, Creaven PJ (1976) 4′-Demethyl-epipodophyllic acid-9- (4,6-0-ethylidene-β-D-glucopyranoside), the major urinary metabolite of VP 16-213 in man. Proc Am Assoc Cancer Res Am Soc Clin Oncol 17:6 (AACR Abstr 21)
Arnold AM (1979) Podophyllotoxin-Derivate VP 16-213. Cancer Chemother Pharmacol 3:71–80
Barlogie B, Drewinko B (1978) Cell cycle stage-dependent induction of G2 phase arrest by different antitumor agents. Eur J Cancer 14:741–745
Bender RA, Zwelling LA, Doroshow JH, Locker GY, Hande KR, Murinson DS, Cohen M, Myers E, Chabner BA (1978) Antineoplastic drugs: clinical pharmacology and therapeutic use. Drugs 16:46–87
Bender RA, De Vita VT jr (1978) Non-Hodgkin's Lymphoma. In: MJ (ed) Staquet Randomized trials in cancer: a critical review by sites. Raven Press, New York, pp 77–102
Bender RA (1979) Vinca alkaloids and epipodophyllotoxins. In: Pinedo HM (ed) Cancer chemotherapy. Excerpta Medica, Amsterdam Oxford, pp 93–106
Bender RA, Anderson T, Fisher RT (im Druck) The activity of the epipodophyllotoxin VP 16 in the treatment of combination chemotherapy-resistant non-Hodgkin's lymphoma. Am J Hematol
Bernasconi C, Lazzarino M, Morra E (1976) The use of an epipodophyllotoxin derivative (VP 16-213) in the treatment of acute monocytic leukaemias. In: Stacher A, Höcker P. Erkrankungen der Myelopoese. Urban & Schwarzenberg, München Berlin Wien, pp 224–227
Bleyer WA, Chard RL, Krivit W, Hammond D (1978) Epipodophyllotoxin therapy of childhood neoplasia: a comperative phase 2 analysis of VM 26 and VP 16-213. Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:373 (ASCO Abstr C 267)
Brewer CF, Loike JD, Horwitz JB, Sternlicht H, Gensler WJ (1979) Conformational analysis of podophyllotoxin and its congeners. Structure-activity relationsip in microtubule assembly. J Med Chem 22:215–221
Brunner KW, Sonntag RW, Ryssel HK, Cavalli F (1976) Comparison of the biologic activity of VP 16-213 given i.v. and orally in capsules or drink ampules. Cancer Treat Rep 60:1377–1379
Brunner K, Jungi W (1979) Mono- and combination chemotherapy with VP 16-213 in small cell lung cancer (SCL). Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:308 (ASCO Abstr 69)
Burchenal JH, Kalaher K, Lokys L, Gale G (1978) Studies of cross-resistance, synergistic combinations, and blocking of activity of platinum derivatives. Biochemie 60:961–965
Burchenal JH, Kalaher K, Dew K, Lokys L (1979) Rationale for development of platinum analogs. Cancer Treat Rep 63:1493–1498
Burchenal JH, Lokys L, Turkevich J, Gale G (1980) Rationale of combination chemotherapy. In: Prestayko AW, Crooke ST, Carter SK (ed) Cisplatin — current status and new developments. Academic Press, New York London Toronto Sydney San Francisco, pp 113–123
Cabanillas F, Gutterman JU, Bodey GP, Freireich EF (1980) Improvement in complete remission (CR) rate and disease-free survival (DFS) of lymphomas by sequential use of non-cross-resistant induction regimens, late intensification (LI), and immunotherapy (IT). Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:466 (ASCO Abstr, C 578)
Cavalli F, Sonntag R, Brunner KW (1975) Epipodophyllotoxin VP 16-213 in acute non-lymphoblastic leukaemia. Br Med J 227
Cavalli F, Ryssell HK, Batz K, Sonntag RW, Brunner KW (1975) Erste Resultate mit dem Epipodophyllotoxin-Derivat VP 16-213 bei der Behandlung akuter Leukämien. Schweiz Med Wochenschr 105:250–253
Cavalli F, Tschopp L, Gerrer A et al. (1977) Therapeutic results using VP 16-213 alone or in combination with 5-fluorouracil in liver cancer (hepatoma). Schweiz Med Wochenschr 107:1960–1966
Cavalli F, Sonntag RW, Jungi F, Senn HK, Brunner KW (1978) VP 16-213 Monotherapy for remission induction of small cell lung cancer: A randomized trial using three dosage schedules. Cancer Treat Rep 62:473–475
Cavalli F, Sonntag RW, Ryssell HJ, Brunner KW (1979) Lack of severe hypotension with VP 16-213 administered directly IV. Cancer Treat Rep 61:1411
Cavalli F, Klepp O, Renard J, Hansen HH, Alberto P (1980) A phase II study of oral VP 16-213 in patients with nonseminomatous testicular cancer. Proc Am Ass Cancer Res Am Soc Clin Oncol 21:137 (AACR Abstr. 154)
Cavalli F, Klepp O, Renard J, Hansen HH, Alberto P (1980) A phase II study of oral VP 16-213 in patients with nonseminomatous testicular cancer. Poster Session AACR Meeting, 28.5.1980, San Diego
Cecil JW, Quagliana JM, Coltman OA, Al-Sarrat M, Thigpen T, Groppe CW (1978) Evaluation of VP 16-23 in malignant lymphoma and melanoma. Cancer Treat Rep 62:801–803
Chakravorty RC, Sarkar SK, Sens S, Mukerji B (1967) Human anticancer effect of podophyllum derivatives (SPG and SPI). Br J Cancer 21:33–39
Chard RL, Krivit W, Bleyer WA, Hammond D (1979) Phase II study of VP 16-213 in childhood malignant disease: A children's cancer study group report. Cancer Treat Rep 63:1755–1759
Chiuten DF, Wodinsky I, Abraham D (1979) Influence of treatment schedule on the toxicity and antitumor activity of mitotic inhibitors and semisynthetic podophyllotoxin derivates. Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:402 (ASCO Abstr C 456)
Cohen MH, Broder LE, Fossiek BE, Ihde DC, Minna JD (1977) Phase II clinical trial of weekly administration of VP 16-213 in small cell bronchogenic carcinoma. Cancer Treat Rep 61:489–490
Creaven PJ, Newman SJ, Selawry OS, Cohen MH, Primack A (1974) Phase I clinical trial of weekly administration of 4′-demethylepipodophyllotoxin 9-(4,6-0-ethylidene-β-D-glucopyranoside) (NSC-141540; VP 16-213). Cancer Chemother Rep 58:901–907
Creaven PJ, Allen LM (1975) EPEG, a new antineoplastic epipodophyllotoxin. Clin Pharm Ther 18:221–256
Dombernowsky P, Nissen NI, Larsen V (1972) Clinical investigation of a new podophyllum derivative, epipodophyllotoxin 4′-demethyl-9-(4,6,0-2-thenylidene-β-D-glucopyranoside) (NSC-122819), in patients with malignant lymphomas and solid tumors. Cancer Chemother Rep 56:71–82
Dombernowsky P, Nissen NI (1973) Schedule dependency of the antileukemic activity of the podophyllotoxin-derivative VP 16-213 (NSC 141540) in L 1210 leukemia. Acta Pathol Microbiol Scand [A]81:715–724
Dombernowsky P, Nissen NI (1976) Combination chemotherapy with 4′-demethylepipodophyllotoxin 9-(4,6-0-ethylidene-β-D-glucopyranoside), VP 16-213 NSC 141540) in L 1210 leukemia. Eur J Cancer 12:181–188
Dorr RT (1979) Incompatibilities with parenteral anticancer drugs. Am J Intravenous Ther 20:42–49
Dorr RT, Fritz WL (1980) Cancer chemotherapy handbook. Elsevier, New York Oxford, pp 418–428
Dorr RT, Fritz WL (1980) Common toxicities. In: Cancer chemotherapy handbook. Elsevier, New York Oxford, pp 75–97
Douglass HO, Lavin PT, Evans JT, Mittelmann A, Carbone PP (1979) Phase II evaluation of diglycoaldehyde, VP 16-213, and the combination of methyl-CCNU and β-2′-deoxythioguanosone in previously treated patients with colorectal cancer: an Eastern Cooperative Oncology Group Study (EST-1275). Cancer Treat Rep 63:1355–1357
Drewinko B, Barlogie B (1976) Survival and cyclo-progression delay of human lymphoma cells in vitro exposed to VP 16-213. Cancer Treat Rep 60:1295–1306
Drewinko B, Green C, Loo TL (1976) Combination chemotherapy in vitro withCis-dichlorodiammineplatinum (II). Cancer Treat Rep 60:1619–1625
Drewinko B, Loo TL, Brown B, Gottlieb JA, Freireich EJ (1976) Combination chemotherapy in vitro with adriamycin, observation of additive antagonistic, and synergistic effects when used in two-drug combinations on cultured human lymphoma cells. Cancer Biochem Biophys 1:187–195
Drewinko B, Barlogie B (1980) Differences in the killing efficacy of antitumor drugs on proliferating (P) and nonproliferating (NP) human cells. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:285 (AACR Abstr. 1142)
Eagan RT, Ahmann DL, Bisel HF (1976) Evaluation of VP 16 and combination of adriamycin and vincristine in advanced breast cancer. Oncology 33:146–148
Eagan RT, Carr DT, Frytak S, Rubin J, Lee RE (1976) VP 16-213 versus polychemotherapy in patients with advanced small cell lung cancer. Cancer Treat Rep 60:949–951
Eagan RT, Ingle JN, Creagan ET, Frytak S, Kvols LK, Rubin J, McMahon RT (1978) VP 16-213 Chemotherapy for advanced squamous cell carcinoma and adenocarcinoma of the lung. Cancer Treat Rep 62:843–844
Eagan RT, Lee RE, Frytak S, Ingle JN, Creagan ET (1980) Combination chemotherapy (CCT) with and withoutcis-diamminedichlorplatinum(II) plus thoracic radiation therapy (TRT) for limited small cell lung cancer (SCLC). Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:131 (ASCO Abstr C 523)
van Echo DA, Wiernik PH, Aisner J (1978) Reinduction therapy for relapsed adult acute non-lymphocytic leukaemia (ANLL) patients. Proc Am Assoc Cancer Res Am Soc Clin Oncol 19:144 (AACR Abstr 575)
Edmonson JH, Decker DG, Malkasian GD, Webb MJ, Jorgensen EO (1978) Phase II avaluation of VP 16-213 (NSC-141540) in patients with advanced ovarian carcinoma resistant to alkylating agents. Gynecol Oncol 6:7–9
EORTC Ovarian Group (1979) Phase II of oral VP-16 in treatment of advanced ovarian carcinoma. Med Oncol 51 (Abstr 72)
European Organization for Research on the Treatment of Cancer, Clinical Screening Group (1973) Epipodophyllotoxin VP 16-213 in treatment of acute leukaemias, haematosarcomas, and solid tumors. Br Med J 3:199–202
Eyben F von, Arwidi A, Mattson W (1980) VP 16-213 in small cell carcinoma of the lung. In: Hansen HH, Dombernovsky P (eds) II. World conference in lung cancer, Abstr. Excerpta Medica, Amsterdam Oxford Princeton, pp 227
Falkson G, Dyk JJ van, Eden EB van, Merwe AM van der, Bergh JA van den, Falkson HC (1975) A clinical trial of the oral form of 4′-demethyl-epipodophyllotoxin-β-D-ethylidene glucoside (NSC 141540) VP 16-213. Cancer 35:1141–1144
Fisher RI, De Vita VT, Hubbard SM, Brennan MF, Chabner BA, Simon R, Young RC (1980) ProcMACE-MOPP combination chemotherapy: treatment of diffuse lymphomas. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:468 (ASCO Abstr. C 589)
Fontana JA (1979) Radiation recall associated with VP 16-213 therapy. Cancer Treat Rep 63:224–225
Getaz EP, Staples WG (1977) Chronic myelomonocytic leukaemia. South Afr Med J 51:852–853
Goldhirsch A, Joss R, Alberto P, Cavalli F, Brunner KW (1980)Cis-platinum (DDP) and VP 16-213 (VP) combination with and without adriamycin (ADM) in the treatment of lung cancer. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:449 (ASCO Abstr. C 514)
Goldhirsch A, Joss RA, Cavalli F, Kaplan S, Sonntag RW, Brunner KW (1980)Cis-dichlorodiammineplatinum(II) and VP 16-213 combination chemotherapy for non small cell lung cancer. Lecture: II. World Conference on Lung Cancer. Copenhagen, June 8–13, 1980
Greenspan EM, Colsky J, Schoenbach EB, Shear MJ (1954) Response of patients with advanced neoplasms to the intravenous administration of alpha-peltatin. J Natl Center Inst 14:1257–1275
Grieder A, Maurer R, Stähelin H (1974) Effect of an epipodophyllotoxin derivative (VP 16-213) on macromolecular synthesis and mitosis in mastocytoma cells in vitro. Cancer Res 34:1788–1793
Grieder A, Maurer R, Stähelin H (1977) Comparative study of early effects of epipodophyllotoxin derivatives and other cytostatic agents on mastocytoma cultures. Cancer Res 37:2998–3005
Gropp C, Havemann K, Gassel WD, Drings P, Mahnke HG, Nagel G, Mitrou PS, Georgii A, Dudeck J (1980) Die Behandlung des kleinzelligen Bronchialkarzinoms mit einer neuen Kombinationschemotherapie (VPIV). In: Burkert H, Nagel GA. (Hrsg). Neue Erfahrungen mit Oxazaphosphorinen unter besonderer Berücksichtigung des Uroprotektors Uromitexan. Karger, Basel München Paris London New York Sydney, pp 70–76
Hahn RG (1977) Megace VP 16-213, Cytoxan and galactitol phase II treatment trials in advanced renal cell cancer. Proc Am Assoc Cancer Res Am Soc Clin Oncol 28:332 (ASCO Abstr C 262)
Hahn RG, Bauer M, Wolter J, Creech R, Bennett JM, Wampler G (1979) Phase II study of single-agent therapy with megestrol acetate, VP 16-213, cyclophosphamide, and dianhydrogalactitol in advanced renal cell cancer. Cancer Treat Res 63:513–515
Hansen H, Hirsch F, Dombernowsky P, Hansen HH (1977) Treatment of small cell anaplastic carcinoma of the lung with the oral solution of VP 16-213 (NSC 141540, 4′-demethylepipodophyllotoxin 9-(4,6-0-ethylidene-β-D-glucopyranoside). Cancer 40:633–637
Havemann K, Gropp C, Gassel WD, Dombrowski H, Fischer M, Mitrou PS (1980) Treatment of small cell lung cancer with a new combination chemotherapy consisting of VP 16-213, iphosphamide, and vindesine (AIO-Study B1). In: Hansen HH, Dombernowsky P (eds) II. World conference of lung cancer, Abstr. Excerpta Medica, Amsterdam Oxford Princeton, pp 152
Holsti LR, Mattson K (1980) Chombination chemotherapy withcis-platinum plus vindesine or VP-16 in epidermoid carcinoma of the lung. In: Nagel G, Prade W, Schmidt CG. Proceedings of the international vinca alkaloid symposium. Karger, Basel (im Druck)
Huang CC, Hou Y, Wang JJ (1973) Effects of a new antitumor agent, epipodophyllotoxin, on growth and chromosomes in human hematopoietic cell lines. Cancer Res 33:3123–3129
Hurd DD, Peterson BA, Bloomfield CD, McKenna RW (1980) VP 16-213 (VP) and cyclophosphamide (CTX) in the treatment of refractory acute nonlymphocytic leukemia (ANLL) with monocytic features. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:439 (ASCO Abstr 476)
Issell BF, Crooke ST (1979) Etoposide (VP 16-213). Cancer Treat Rev 6:107–124
Jackson DV, Bender RA (1978) The clinical pharmacology of the vinca alkaloids, epipodophyllotoxins, and maytansine. In: Pinedo HM (ed) Clinical pharmacology of anti-neoplastics drugs. Elsevier North-Holland Biomedical Press, Amsterdam New York Oxford, pp 277–293
Jacobs P, King HS, Sealy GRH (1975) Epipodophyllotoxin (VP 16-213) in the treatment of diffuse histiocytic lymphoma. S Afr Med J 49:483–485
Jacobs P, Dubovsky D, Hougaard M, Comay S (1975) Epipodophyllotoxin VP 16-213 in acute non-lymphoblastic leukaemia. Br Med J 396
Jacobs P, King H, Cassidy F, Dent D (1979) The treatment of diffuse lymphocytic lymphoma (large cell) with VP 16-213. Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:289 (AACR Abstr 1179)
Jungi WF, Senn HJ, Beckmann C, Flury R, Frei P, Holdener E (1975) Therapeutische Erfahrungen mit dem neuen Podophyllotoxinderivat VP 16-213 bei menschlichen malignen Tumoren. Schweiz Med Wochenschr 105:1365–1369
Jungi WF, Senn HJ (1975) Clinical study of the new podophyllotoxin derivative, 4′-demethylepipodophyllotoxin 9-(4,6-0-ethylidene-β-D-glucopyranoside) (NSC-141540; VP 16-213), in solid tumors in man. Cancer Chemother Rep 59:737–742
Kaplan IW (1942) Condylomata acuminata. New Orleans Med Surg J 94:388–390
Keller-Juslen C, Kihn M, von Wartburg A, Stähelin H (1971) Synthesis and antimitotic activity of glycosidic lignan derivatives related to podophyllotoxin. J Med Chem 14:936–940
Kelly MG, Hartwell JL (1954) The biological effects and the chemical comparison of podophyllin. A Review. J Natl Cancer Inst 14:967–1010
Krishan A, Paika K, Frei E (1975) Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM 26, VP 16-213) on the cell cycle traverse of human lymphoblasts. J Cell Biol 66:521–530
Labedzki L, Illiger HJ (1979) Erfolgreiche Behandlung der chronischen myelomonozytären Leukämien mit VP 16-213. Blut 38:421–424
Lau ME, Hansen HH, Pedersen H (1979) Phase I trial of a new form of oral administration of VP 16-213. Cancer Treat Rep 63:485–487
Löffler H, Ganzer U (1976) Erfahrungen mit VP 16-213 bei Monozytenleukämie. In: Stacher A, Höcker P (Hrsg) Erkrankungen der Myelopoese. Urban & Schwarzenberg, München Berlin Wien, pp 221–223
Loike JD, Horwitz SB (1976) Effects of podophyllotoxin and VP 16-213 on microtubule assembly in vitro and nucleoside transport in hela cells. Biochemistry 15:5435–5442
Loike JD, Horwitz SB (1976) Effect of VP 16-213 on the intracellular degradation of DNA in hela cells. Biochemistry 15:5443–5448
Loike JD, Brewer CF, Sternlicht H, Genster WJ, Horwitz SB (1978) Structure- activity study of the inhibition of microtubule assembly in vitro by podophyllotoxin and its congeners. Cancer Res 38:2688–2693
Lokich J, Corkery J (1980) Protacted venous infusion (PVI) of VP 16, vinblastine (VLB),cis-platinum (CDPP), or cyclophosphamide (CTX). Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:144 (AACR Abstr 575)
Longeval E, De Jager R, Tagnon H, Klastersky J (1980)cis-platin (CDDP)-VP 16-213 combination chemotherapy in non small-cell (NSC) bronchogenic carcinoma: phase I–II clinical trial. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:368 (ASCO Abstr C 195)
Look T, Dahl G, Rivera G, Kalwinsky D, Mason C (1980) Effective remission induction of refractory childhood acute nonlymphocytic leukemia (ANLL) with the combination of VP 16-213 (VP 16) and 5-azacytidine (5AZ). Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:435 (ASCO Abstr C 461)
Mabel JA, Little AD (1979) Therapeutic synergism in murine tumors for combinations of cis-diamminedichloroplatinum with VP 16-213 or BCNU. Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:230 (AACR Abstr 929)
Mathe G, Schwarzenberg L, Pouillart P, Weiner R, Oldham R, Jasmin C, Rosenfeld C, Hayat M, Schneider M, Amiel JL, Ce'Ora B, Stereco-Musset M, de Vassal F (1974) Acute leukaemia and various hematosarcomas. Trial treatment with 4-demethyl-epipodophyllotoxin beta D ethylidene glucoside VP 16-213. Nouv Presse Med 3:521–524
Mathé G, Schwarzenberg L, Poullart P, Oldham R, Weiner R, Jasmin C, Rosenfeld C, Hayat M, Misset JL, Musset M, Schneider M, Amiel JL, De Vassal F (1974) Two epipodophyllotoxin derivatives VM 26 and VP 16-213 in the treatment of leukaemias, hematosarcomas, and lymphomas. Cancer 34:985–992
Minna J, Ihde D, Bunn P, Cohen M, Fossiek B, Mathews M (1980) Extensive stage small cell carcinoma of the lung (SCCL): effect of increasing intensity of induction chemotherapy. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:448 (ASCO Abstr C 510)
Minna JD, Ihde D, Bunn PA, Cohen M, Fossiek B, Matthews MJ (1980) Extensive stage small cell carcinoma of the lung: Effect of increasing intensity of induction chemotherapy. In: Hansen HH, Dombernowsky P (eds) II. World conference on lung cancer, abstr. Excerpta Medica, Amsterdam Oxford Princeton, pp 160
Natale R, Hilaris B, Golbey R, Wittes R (1979) Induction chemotherapy in small carcinoma of the lung (SCCL). Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:343 (ASCO Abstr 214)
Natale R, Hilaris B, Wittes R (1980) Prolonged remission of small cell lung carcinoma (SCCL) with intensive chemitherapy induction and high dose radiation therapy without maintenance. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:452 (ASCO Abstr C 525)
Natale R, Hilaris B, Wittes R (1980) Prolonged remission of small cell lung carcinoma (SCLC) with intensive chemotherapy induction and high dose radiation therapy without maintenance. Lecture Proc Am Assoc Cancer Res Am Soc Clin Oncol San Diego May 27 1980
Natale R, Hilaris B, Shank B, Wittes R (1980) Prolonged remission of small cell lung carcinoma (SCLC) with intensive chemotherapy induction and high dose radiation therapy without maintenance. In: Hansen HH, Dombernowsky P (eds) II. World Conference on Lung Cancer, Abstr. Experpta Medica, Amsterdam Oxford Princeton, pp 16
Newlands ES, Bagshawe KD (1977) Letter: Epipodophyllin derivative (VP 16-213) in malignant teratomas and choriocarcinomas. Lancet 2:87
Newlands ES, Bagshawe KD (1980) Anti-Tumour activity of the epipodophyllin derivative VP 16-213 (etoposide: NSC-141540) in gestational choriocarcinoma. Eur J Cancer 16:401–403
Newlands ES, Fitzharris BM, Kaye SB, Barret A, Peckham MJ, McElwain TJ (1980) VP 16-213 as a single agent in advanced testicular tumors. Int J Cancer 16 (im Druck)
Nissen NI, Larsen V, Pedersen H, Thomsen K (1972) Phase I clinical trial of a new antitumor agent, 4′-demethylepodophyllotoxin 9-(4,6-0-ethylidene-β-D-glucopyranosid (NSC-141540); VP 16-213. Cancer Chemother Rep 56:769–777
Nissen NI, Hansen HH, Pedersen H, Stroyer I, Dombernowsky P, Hesselund M (1975) Clinical trial of the oral form of a new podophyllotoxin derivate, VP 16-213 (NSC-141540), in patients with advanced neoplastic disease. Cancer Chemother Rep 59:1027–1029
Nissen NI, Dombernowsky P, Hansen HH, Larsen V (1976) Phase I clinical trial of an solution of VP 16-213. Cancer Chemother Rep 60:943–944
Nissen NI, Pajak TF, Leone LA, Bloomfield CI, Kennedy BJ, Ellison RR, Silver RT, Weiss RB, C ner J, Falkson G, Kung F, Bergevin PR, Holland J (1980) Clinical trial of VP 16-213 (NSC 141540) I.V. twice weekly advanced neoplastic dissease. Cancer 45:232–235
O'Connell MJ, Silverstein MN, Kiely JM, White WL (1977) Pilot study of two adriamycin-based regimens in patients with advanced malignant lymphomas. Cancer Treat Rep 61:65–68
Odom LF, Rose B, Tubergen DG (1979) A successful induction regimen for childhood acute non-lymphoblastic leukaemia (ANLL). Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:440 (ASCO Abstr 619)
Perry MC, Moertel CG, Schutt AJ (1976) Phase II studies of dianhydrogalactitol and VP 16-213 in colorectal cancer. Cancer Treat Rep 60:1247–1250
Radice PA, Bunn PA, Ihde DC (1979) Therapeutic trials with VP 16-213 and VM 26: active agents in small cell lung cancer. non Hodgkin's lymphomas and other malignancies. Cancer Treat Rep 63:1231–1239
Rao PN (1979) G2Arrest Induced by Anticancer Drugs. In: Busch H, Crooke ST, Daskal Y (eds) Effects of drugs on the cell nucleolus. Academic Press, New York London Toronto Sydney San Francisco, pp 475–490
Rivera G, Avery T, Roberts DW (1975) Response of L 1210 to combinations of cytosine arabinoside and VM 26 or VP 16-213. Eur J Cancer 11:639–647
Rivera G, Avery T, Pratt C (1975) 4′-Demethylepipodophyllotoxin, 9-(4,6-0-2-thenylidene-β-D-glucopyranoside) (NSC-122819; VM 26) and 4′-demethylepipodophyllotoxin 9-(4,6-0-ethylidene-β-D-glucopyranoside) (NSC 141540; VP 16-213) in childhood cancer: preliminary observations. Cancer Chemother Rep 59:743–749
Rozencweig M, V Hoff D, Henney JE, Muggia FM (1977) VM 26 and VP 16-213: A comparative analysis. Cancer 40:334–342
Sandoz Pharma (1976) Zusammenfassung VP 16-213 Pharmakokinetik
Sandoz Pharma (1979) VP 16-213 Zusammenfassung Präklinische Pharmakologie
Sandoz Pharma (1979) VP 16-213 Chemie, Pharmakologie, Präklinische Zusammenfassung
Schabel FM, Trader MW, Laster WR, Corbett TH, Griswold DP (1979)Cis-dichlorodiammineplatinum(II): combination chemotherapy and cross-resistance studies with tumors of mice. Cancer Treat Rep 63:1459–1473
Schechter JP, Jones SE (1979) Myocardial infarction in a 27-year-old woman: possible complication of treatment with VP 16-213 (NSC 141540) mediastinal irradiation, or both. Cancer Chemother Rep 59:887–888
Sieber SM, Mead JAR, Adamson RH (1976) Pharmacology of antitumor agents from higher plants. Cancer Treat Rep 60:1127–1139
Sieber SM, Whang-Peng J, Botkin C, Knutsen T (1978) Teratogenic and cytogenetic effects of some plant-derived antitumor agents (vincristine, colchicine, maytansine, VP 16-213 and VM 26) in mice. Teratology 18:31–48
Sierocki JS, Golbey RB, Wittes RE (1978) Combination chemotherapy for small cell carcinoma of the lung (SCCL). Proc Am Assoc Cancer Res Am Soc Clin Oncol 19:352 (ASCO Abstr C 182)
Sierocki JS, Hilaris BJ, Hopfan S, Martini N, Barton D, Golbey RB, Wittes RB (1979)Cis-diamminedichloroplatinum II and VP 16; an active induction regimen for small cell carcinoma of the lung. Cancer Treat Rep 63:1593–1597
Slayton R, Creasman W, Bundy B (1979) Phase II trial of VP 16 in treatment of advanced squamous cell carcinoma of the cervix. Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:365 (ASCO Abstr C 305)
Slayton R, Petty W, Blessing J (1979) Phase II trial of VP 16 in treatment of advanced adenocarcinoma. Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:190 (AACR Abstr 768)
Smith IE, Gerken ME, Clink HM, McElwain TJ (1976) VP 16-213 in acute myelogenous leukaemia. Postgrad Med J 52:66–70
Snodgrass W, Walker L, Heideman R, Odom LF, Hays T, Tubergen DG (1980) Kinetics of VP 16 epipodophyllotoxin in children with cancer. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:333 (ASCO Abstr C 58)
Soloway MS, Masters SB, Murphy WM (1980)Cis-platin analogs and combination chemotherapy in the therapy of murine bladder cancer. In: Prestayko AW, Crooke ST, Carter SK (eds)Cis-platin — current status and new developments. Academic Press, New York London Toronto Sydney San Francisco, pp 345–359
Stähelin H (1973) Activity of a new glycosidic lignan derivative (VP 16-213) related to podophyllotoxin in experimental tumors. Eur J Cancer 9:215–221
Stähelin H (1976) Delayed toxicity of epipodophyllotoxin derivatives (VM 26 and VP 16-213), due to a local effect. Eur J Cancer 12:925–931
Stewart P, Bagley C, Einstein A, Rudolph R (1980) Intensive drug therapy for small cell bronchogenic carcinoma. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:455 (ASCO Abstr C 538)
Sullivan BJ, Wechsler I (1947) The cytological effects of podophyllin. Science 105:433–435
Sullivan M (1949) Treatment of cutaneous carcinoma with podophyllin Preliminary note. Bull Johns Hopkins Hosp 85:200–203
Tempero M, Foley JF, Kessinger A (1980) VP 16-213 after failure with combination chemotherapy for small cell carcinoma of the lung. Proc Am Assoc Cancer Res Am Soc Clin Oncol 21:460 (ASCO Abstr C 556)
Tucker RD, Ferguson A, van Wyks C, Sealy R, Hewitson R, Levin W (1978) Chemotherapy of small cell carcinoma of the lung with VP 16-213. Cancer 41:1710–1714
Vaitkevicius VK, Reed ML (1966) Clinical studies with podophyllum compounds SPI-77 (NSC-72274) and SPG-827 (NSC-42076). Cancer Chemother Rep 50:565–571
Wellens W, Mussgnug G, Habets L, Schäfer E, Westerhausen M (1980) Die Kombination Ifosfamid/VP 16-213 bei der Therapie des kleinzelligen Bronchialkarzinoms und anderer Malignome. In: Neue Erfahrungen mit Oxazaphosphorinen unter besonderer Berücksichtigung des Uroprotektors Uromitexan. Karger, Basel München Paris London New York Sydney, pp. 84–90
Williams, D, Einhorn LH, Greco A, Oldham R, Fletcher R, Bond WH (1979) VP 16-213: An active drug in germinal neoplasms. Proc Am Assoc Cancer Res Am Soc Clin Oncol 20:72 (AACR Abstr 291)
Williams SD, Einhorn LH (1980) VP 16-213: An active drug in germinal neoplasms. In: Einhorn LH (ed) Testicular tumors management and treatment. Masson, New York Paris Barcelona Milan Mexico City Rio de Janeiro, pp 169–177
Wolpert-De Filippes MK (1979) Antitumor activity ofcis-dichlorodiammineplatinum (II). Cancer Treat Rep 63:1453–1458
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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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DOI: https://doi.org/10.1007/BF01721212