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Teniposide: overview of its therapeutic potential in adult cancers

  • Session 3: Clinical Trials and Applications
  • Teniposide, Solid Tumors, Epipodophyllotoxin
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Teniposide was introduced into clinical trials prior to etoposide, but its role was not defined because interest shifted early on to etoposide. However, long-term encouraging results obtained in acute leukemia treated with teniposide have rekindled interest in this compound. In addition to pharmacokinetic differences, teniposide has greater CNS penetrance and is more lipophilic. Its greater potency is related to enhanced intracellular uptake. Although its antitumor spectrum of activity appears to be very similar to that of etoposide, a search for some differences might prove instructive.

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References

  1. Beck WT (1989) Unknotting the complexities of multidrug resistance: the involvement of DNA topoisomerases in drug action and resistance. J Natl Cancer Inst 81: 1683

    Google Scholar 

  2. Bhuchar VK, Boyle LE, Lanzotti VJ (1978) VM-26 in non-oat cell bronchogenic carcinoma (abstract C-404). Proc Am Assoc Cancer Res/Proc Am Soc Clin Oncol 19: 407

    Google Scholar 

  3. Bork E, Hansen M, Dombernowsky P, Hansen SW, Pedersen AG, Hansen HH (1986) Teniposide (VM-26) an overlooked highly active agent in small-cell lung cancer: results of a phase II trial in untreated patients. J Clin Oncol 4: 525

    Google Scholar 

  4. Bork E, Ersball J, Dombernowsky P, Bergman B, Hansen M, Hansen HH (1991) Teniposide and etoposide in previously untreated small-cell lung cancer: a randomized study. J Clin Oncol 9: 1627

    Google Scholar 

  5. Burg MEI van der, Ten Bokkel Huinink WW, Vriesendorp R, Van Oosterom RT, Neijt JP, Vermoken JB, van Putten WL, Kooiman A (1987) Teniposide (VM-26) in patients with advanced refractory ovarian cancer: a phase II study of the Netheralands Joint Study Group for Ovarian Cancer. Eur J Cancer Clin Oncol 23: 997

    Google Scholar 

  6. Cerny T, Pedrazzini A, Joss RA, Brunner KW (1988) Unexpected high toxicity in a phase II study of teniposide (VM-26) in elderly patients with untreated small cell lung cancer (SCLC). Eur J Cancer Clin Oncol 24: 1791

    Google Scholar 

  7. Chakravorty RC, Serkar AK, Sen S, Mukerji B (1967) Human anticancer effect of podophyllum derivatives (SPG and SPI): a preliminary report. Br J Cancer 21: 33

    Google Scholar 

  8. Chiuten DF, Bennett JM, Creech RH, Glick J, Falkson G, Brodovsky HS, Begg CB, Muggia FM, Carbone P (1979) VM-26, a new anticancer drug with effectiveness in malignant lymphoma: an Eastern Cooperative Oncology Group study (EST 1474). Cancer Treat Rep 63: 7

    Google Scholar 

  9. Clark PI (1992) Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. Semin Oncol 19 [Suppl 6]: 20

    Google Scholar 

  10. Creech RH, Tritchler D, Ettinger DS, Ferraro JA, Ruckdeschel JC, Vogl SE, Woll J (1984) Phase II study of PALA, amsacrine, teniposide and zinostatin in small cell lung carcinoma (EST 2579). Cancer Treat Rep 68: 1183

    Google Scholar 

  11. deVries EGE, Mulder NH, Postmus PE, Vriesendorp R, Villemse PH, Sleijfer DT (1986) High dose teniposide for refractory malignancies: a phase I study. Cancer Treat Rep 70: 595

    Google Scholar 

  12. Dombernowsky P, Nissen NI, Larsen V (1972) Clinical investigation of a new podophyllin derivative, VM 26, in patients with malignant lymphomas and solid tumors. Cancer Chemother Rep 5: 71

    Google Scholar 

  13. European Organization for Research on the Treatment of Cancer (1972) Cooperative Group for Leukaemias and Haematosarcomas: clinical screening of epipodophyllotoxin VM-26 in malignant lymphomas and solid tumors. BMJ 2: 744

    Google Scholar 

  14. Giaccone G, Donadio M, Bonardi G, Testore F, Calciati A (1988) Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy. J Clin Oncol 6: 1264

    Google Scholar 

  15. Glisson BS, Sullivan DM, Gupta R, Ross WE (1987) Mediation of multi-drug resistance in a Chinese hamster ovary cell line by a mutant type II topoisomerase. NCI Monogr 4: 89

    Google Scholar 

  16. Goldman ID, Yalowich JC (1984) Effects of epipodophyllotoxins on membrane transport and transport-dependent intracellular processes in the Ehrlich ascites tumor: enhancement of transport and metabolism of methotrexate; inhibition of thymidine transport and metabolism. In: Issell BF, Muggia FM, Carter SK (eds) Etoposide (VP-16): current status and new developments. Academic Press, New York, p 87

    Google Scholar 

  17. Greenspan EM, Colsky J, Schoenbach B, Shear MJ (1954) Response of patients with advanced neoplasms to the intravenous administration of alpha-peltatin. J Natl Cancer Inst 14: 1257

    Google Scholar 

  18. Grossberg H, Opfell R, Glick J, Bakemeier R, Schnetzer G III, Muggia F (1987) Treatment of advanced refractory lymphoma with teniposide and lomustine. Cancer Treat Rep 71: 215

    Google Scholar 

  19. Gutin PH, Walker MD (1977) IV methyl-CCNU, VM26 and cranial irradiation in therapy for malignant brain tumors. Cancer Treat Rep 61: 1715

    Google Scholar 

  20. Holoye PY, Winn RJ, Craig K, Goodwin W, Wade J, Cammon MW (1989) Phase II study of teniposide in small cell bronchogenic carcinoma (abstract 946). Proc Am Soc Clin Oncol 8: 243

    Google Scholar 

  21. Howell SB, Hom D, Sanga R, Vick JS, Abramson IS (1989) Comparison of the synergistic potentiation of etoposide, doxorubicin, and vinblastine cytotoxicity by dipyridamole. Cancer Res 49: 3178

    Google Scholar 

  22. Issell BF, Muggia FM, Carter SK (eds) (1984) Etoposide (VP-16): current status and new developments. Academic Press, New York p 355

    Google Scholar 

  23. Jacobs P (1985) The epipodophyllotoxin VP-16-213 in combination chemotherapy for adults with acute non-lymphoblastic leukemia. Hamatol Bluttransfus 29: 70

    Google Scholar 

  24. Jankowski RP, Vahrson H (1977) Die Toxizität hoher Dosen von VM26 (4-Demethyl-epipodophyllotoxin-β-D-thenylidene glucoside). Med Klin 72: 122

    Google Scholar 

  25. Kelly MG, Hartwell JL (1954) The biological effects and chemical composition of podophyllin. A review. J Natl Cancer Inst 14: 967

    Google Scholar 

  26. Kerrigan D, Pommier Y, Kohn KW (1987) Protein-linked DNA strand breaks produced by etoposide and teniposide in mouse L1210 and human VA-13 and HT 29 cell lines: relationship to cytotoxicity. NCI Monogr 4: 123

    Google Scholar 

  27. Laubenstein LJ, Krigel RL, Odajnik CM, Hymes KB, Freidman KA, Wernz JC, Muggia FM (1984) Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin and vinblastine. J Clin Oncol 2: 1115

    Google Scholar 

  28. Lee T, Roberts D (1983) Uptake as a determinant of resistance to teniposide (VM-26). Fed Proc 42: 768

    Google Scholar 

  29. Loike JD, Horwitz SB (1976) Effect of VP 16-213 on the intracellular degradation of DNA in HeLa cells. Biochemistry 15: 55443

    Google Scholar 

  30. Loike JD, Brewer CF, Sternlicht H, Gensler WJ, Horwitz SB (1978) Structure-activity of the inhibition of microtubule assembly in vitro by podophyllotoxin and its congeners. Cancer Res 38: 2688

    Google Scholar 

  31. Long BH (1991) Mechanisms of action of teniposide (VM-26) and comparison with etoposide (VP-16). Semin Oncol 18 [Suppl 4]: 3

    Google Scholar 

  32. Long BH, Minocha A (1983) Inhibition of topoisomerase II by VP 16-213 (etoposide), VM 26 (teniposide), and structural congeners as an explanation for in vivo DNA breakage and cytotoxicity. Proc Am Assoc Cancer Res 24: 321

    Google Scholar 

  33. Mathe G, Schwartzenberg L, Pouillart P, Oldham R, Weiner R, Jasmin C, Rosenfeld C, Hayat M, Misset JL, Musset M, Schneider M, Amiel JL, DeVassal F (1974) Two epipodophyllotoxin derivatives, VM26 and VP 16213, in the treatment of leukemia, hematosarcomas, and lymphomas. Cancer 34: 985

    Google Scholar 

  34. Muggia FM, Kelley SL (1992) Teniposide in adult solid tumors: a historical perspective. Semin Oncol 19 [Suppl 6]: 43

    Google Scholar 

  35. Muggia FM, Russell CA (1991) New chemotherapies for ovarian cancer: systemic and intraperitoneal podophyllotoxins. Cancer 67 [Suppl 1]: 225

    Google Scholar 

  36. Muggia FM, Selawry OS, Hansen HH (1971) Clinical studies with a new podophyllotoxin derivative, epipodophyllotoxin, 4′-demethyl-9-(4,6-O-2-thenylidene-β-D-glucopyranoside) (NSC-122819). Cancer Chemother Rep 55: 575

    Google Scholar 

  37. Muss H, Bundy BN, Yazigi R, Yordan E (1987) Teniposide in squamous cell carcinoma of the cervix: a phase II trial of the Gynecologic Oncology Group. Cancer Treat Rep 71: 873

    Google Scholar 

  38. Newlands ES, Bagshawe KD (1977) Epipodophyllin derivative (VP16-213) in malignant teratomas and choriocarcinomas. Lancet II: 87

    Google Scholar 

  39. Pedersen AG, Hansen HH (1983) Etoposide (VP-16) in the treatment of lung cancer. Cancer Treat Rev 10: 245

    Google Scholar 

  40. rodman JH, Abromowitch M, Sinkule JA, Hayes FA, Rivera GK, Evans WE (1985) Clinical pharmacodynamics of continuous infusion teniposide: systemic exposure as a determinant of response in a phase I trial. J Clin Oncol 5: 1007

    Google Scholar 

  41. Ross WE, Rowe T, Glisson B, Yalowich J, Liu L (1984) Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage. Cancer Res 44: 5857

    Google Scholar 

  42. Rowe T, Kupfer G, Ross W (1985) Inhibition of epipodophyllotoxin cytotoxicity by interference with topoisomerase-mediated DNA cleavage. Biochem Pharmacol 34: 2483

    Google Scholar 

  43. Rozencweig M, Von Hoff DD, Henney J, Muggia FM (1977) VM-26 and VP 16-213: a comparative analysis. Cancer 40: 334–342

    Google Scholar 

  44. Ryan DH, Kopecky KJ, Head D, Gumbert CN, Grever MR, Karanaes C, Weick JK, Coltman CA Jr (1987) Phase II evaluation of teniposide and ifosfamide in refractory adult acute lymphocytic leukemia: a Southwest Oncology Group study. Cancer Treat Rep 71: 713

    Google Scholar 

  45. Samson MK, Baker LH, Talley RW, Fraile RJ (1978) VM26 (NCS-122819): a clinical study in advanced cancer of the lung and ovary. Eur J Cancer 14: 1395

    Google Scholar 

  46. Sanz GF, Sanz MA, Rafecas FJ, Martinez JA, Martin-Aragones G, Marty ML (1986) Teniposide and cytarabine: combination chemotherapy in the treatment of relapsed adolescent and adult acute lymphoblastic leukemia. Cancer Treat Rep 70: 1321

    Google Scholar 

  47. Schwartsmann G, Sprinz E, Kronfeld M, Vinholes J, Sander E, Zampese M, Preger R, Klakun L, Brunetto AL (1991) Phase II study of teniposide in patients with AIDS-related Kaposi's sarcoma. Eur J Cancer 27: 1637

    Google Scholar 

  48. Sessa C, D'Incalci M, Landoni F, Rossi C, Urso R (1986) Teniposide in refractory ovarian cancer: a phase II study. Cancer Treat Rep 68: 815

    Google Scholar 

  49. Sinha BK, Eliot HM, Kalayanaraman B (1988) Iron-dependent hydroxyl radical formation and DNA damage from a novel metabolite of the clinically active antitumor drug VP-16. FEBS Lett 227: 240

    Google Scholar 

  50. Sklansky BD, Mann-Kaplan RS, Reynolds AF, Rosenblum ML, Walker MD (1974) 4′-Demethyl-epipodophyllotoxin-β-D-thenylidene-glucoside (PTG) in the treatment of malignant intracranial neoplasms. Cancer 33: 460

    Google Scholar 

  51. Slevin ML, Clark PI, Joel SP, Osborne WM, Gregory WM, Lowe RH, Reznek RH, Wrigley PFM (1989) A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. J Clin Oncol 7: 1333

    Google Scholar 

  52. Sörensen JB, Bach F, Dombernowsky P, Hansen HH (1991) Phase II study of teniposide in adenocarcinoma of the lung. Cancer Chemother Pharmacol 27: 487

    Google Scholar 

  53. Sonneveld P (1992) Teniposide in lymphomas and leukemias. Semin Oncol 19 [Suppl 6]: 59

    Google Scholar 

  54. Sonntag RW, Senn HJ, Nagel G, Giger K, Alberto P (1974) Experience with 4′-demethyl epipodophyllotoxin 9-(4,6-O-2-thenylidene-beta-D-glucopyranoside); VM-26; NSC-122819 in the treatment of malignant lymphosis. Eur J Cancer 10: 93

    Google Scholar 

  55. Stähelin HF, Wartburg A von (1991) The chemical and biological route from podophyllotoxin glucoside to etoposide: Ninth Cain Memorial Award Lecture. Cancer Res 51: 5

    Google Scholar 

  56. Stoter G, Oosterom AT van, Mulder JH, dePauw M, Fossa SD (1984) Combinaton chemotherapy with cisplatin and VM-26 in advanced transitional cell carcinoma of the bladder. Eur J Cancer Clin Oncol 20: 315

    Google Scholar 

  57. Sullivan DM, Chow K-C, Glisson BS, Ross WE (1987) Role of proliferation in determining sensitivity to topoisomerase II-active chemotherapy agents. NCI Monog 4: 73

    Google Scholar 

  58. Tirelli U, Carbone A, Franchini G, Galligioni E, Veronesi A, Trovo MG, Volpe R, Tumolo S, Grigoletto E (1982) VM26 in malignant hematological diseases: a phase II study. Cancer Chemother Pharmacol 7: 173

    Google Scholar 

  59. Trempe G, Sykes M, Young C, Krakoff I (1970) Phase I trial of the podophyllotoxin derivative VM-26. Proc Am Assoc Cancer Res 11: 79

    Google Scholar 

  60. Vaitkevicius VK, Reed ML (1966) Clinical studies with podophyllum compounds SPI-77 (NSC-72274) and SPG-827 (NSC-42076). Cancer Chemother Rep 50: 565

    Google Scholar 

  61. Warrell RP Jr, Straus DJ, Young CW (1982) Combination chemotherapy for patients with relapsed malignant lymphoma using methyl-GAG and teniposide (VM-26). Cancer Treat Rep 66: 1121

    Google Scholar 

  62. Woods RL, Fox RM, Tattersall MHN (1979) Treatment of small cell bronchogenic carcinoma with VM-26. Cancer Treat Rep 63: 2011

    Google Scholar 

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  1. University of Southern California, Norris Cancer Center, 1441 Eastlake Avenue, 90033, Los Angeles, CA, USA

    Franco M. Muggia

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Muggia, F.M. Teniposide: overview of its therapeutic potential in adult cancers. Cancer Chemother. Pharmacol. 34 (Suppl 1), S127–S133 (1994). https://doi.org/10.1007/BF00684876

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