Skip to main content
Log in

Vinorelbine and the topoisomerase 1 inhibitors: Current and potential roles in breast cancer chemotherapy

  • New agents in breast cancer — minisymposium
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Vinorelbine is a semi-synthetic vinca alkaloid which was initially developed in France in the 1980's. Due to its unique structure it is considerably less neurotoxic than vincristine. Several phase II studies have shown that vinorelbine is active in metastatic breast cancer therapy with response rates of 20–30% in pretreated and 40–50% in nonpretreated patients respectively. Higher response rates have been noted when vinorelbine is used in combination regimens. The main dose-limiting toxicity seen with this agent has been neutropenia; neurotoxicity manifest as symptomatic paresthesia can be seen in 10% of treated patients. Oral and implantable forms of the drug have also been investigated.

The topoisomerase 1 inhibitors topotecan and camptothecin 11 (CPT-11) have been less extensively evaluated in breast cancer therapy. Preclinical studies have indicated that both of these agents are active against breast cancer and some responses have been seen in phase 1 trials of topotecan. An 8% response rate was noted in a phase II trial of CPT-11 in patients with pretreated metastatic breast cancer. Further phase II trials are ongoing at present with both agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Valagusa P, Bonadonna G, Veronesi A: Patterns of relapse and survival after radical mastectomy. Cancer 41:1170, 1978.

    Google Scholar 

  2. Fisher B, Slack N, Katrych D, Wolmark N: Ten year follow up results of patients with carcinoma of the breast in a cooperative clinical trial evaluating surgical adjuvant chemotherapy. Surg Gynecol Obstet 140:528, 1975.

    Google Scholar 

  3. Johnson IS, Armstrong JG, Gorman M, Burnett JP: The vinca alkaloids: a new class of oncolytic agents. Cancer Res 23:1390–1427, 1963.

    Google Scholar 

  4. Potier P: The synthesis of navelbine prototype of a new class of vinblastine derivatives. Semin Oncol 16(Suppl 4):2–4, 1989.

    Google Scholar 

  5. Budman DR: New vinca alkaloids and related compounds. Semin Oncol 19(6):639–645, 1992.

    Google Scholar 

  6. Bryan J: Definition of 3 classes of binding sites in isolated microtubule crystals. Biochem 11:2611–2616, 1972.

    Google Scholar 

  7. Strychmans PA, Lune PM, Manaster J, Vameca G: Mode of action of chemotherapy in vivo on human acute leukemia II. Vincristine. Eur J Cancer 9:613–620, 1973.

    Google Scholar 

  8. Borman LS, Kuehne ME: Specific alterations in the biological activities of C-20-modified vinblastine congeners. Biochem Pharmacol 38:715–724, 1989.

    Google Scholar 

  9. Binet S, Fellows A, Lanaste H, Krikorian A, Couzinier JP, Meninger V:In situ analysis of the action of navelbine on various types of microtubules using immunofluorescence. Semin Oncol 16(2):5–8, 1989.

    Google Scholar 

  10. Houghton JA, Williams LG, Dodge R, George S, Hazelton BJ, Houghton PJ: Relationship between binding affinity retention and sensitivity of human rhabdomyosarcoma xenografts to vinca alkaloids. Biochem Pharmacol 36:81–88, 1987.

    Google Scholar 

  11. Krikorian A, Rahmani R, Bromet M, Bore P, Cano JP: Pharmacokinetics and metabolism of navelbine. Semin Oncol 16:21–25, 1989.

    Google Scholar 

  12. Urien S, Bree F, Breillout F, Bastian G, Krikorian A, Tillement JP: Vinorelbine high affinity binding to human platelets and lymphocytes: distribution in human blood. Cancer Chemother Pharmacol 32:231–234, 1993.

    Google Scholar 

  13. Rahmani R, Bore P, Favre R: Preliminary studies on vindesine and navelbine metabolisms using human isolated hepatocytes and microsomal fractions. Proc 5th NCI/EORTC Symposium on New Drugs in Cancer Therapy, Amsterdam, Oct.22–24, 1992, 10:12 (abstract).

  14. Nelson RL, Dyke RW, Root MA: Comparative pharmacokinetics of vindesine, vincristine and vinblastine in patients with cancer. Cancer Treat Rev 7(Suppl): 17–24, 1980.

    Google Scholar 

  15. Rahmani R, Bore P, Cano JP, Herrara A, Krikorian A: Phase I trial of escalating doses of orally administered navelbine, part 1: Pharmacokinetics. Proc Am Soc Clin Oncol 8:74, 1989 (abstract).

    Google Scholar 

  16. Lucas S, Donehower R, Rowinsky E, Trump D, Weiner E, Wargin W, Hohneker J, Hsieh A: Clinical results of a study of the absolute bioavailability and pharmacokinetics of weekly navelbine liquid filled soft gelatin capsules at full therapeutic doses in patients with solid tumors. Proc Am Soc Clin Oncol 11:267, 1992 (abstract).

    Google Scholar 

  17. Queiber W, Doss A, Wander HE: Phase II study of vinorelbine by oral route (in a hard gelatin capsule) for metastatic breast cancer patients. Onkologie 14:35–39, 1991.

    Google Scholar 

  18. Fournier C, Hecquet B, Bouffard P, Vert M, Caty A, Vilain MO, Vanseymortier L, Merle S, Krikorian A, Lefebvre JL, Delobelle A, Adenis L: Experimental studies and preliminary clinical trial of vinorelbine loaded polymeric implants for the local treatment of solid tumors. Cancer Res 51:5384–5391, 1991.

    Google Scholar 

  19. Cabral FR, Brady RC, Schiber MJ: A mechanism of cellular resistance to drugs that interfere with microtubule assembly. Ann NY Acad Sci 466:745–756, 1986.

    Google Scholar 

  20. Adam DJ, Knick VC: MDR and nonMDR forms of cellular resistance to 5'nor-anhydrovinblastine (vinorelbine). Proc Am Assoc Cancer Res 33:462, 1992 (abstract).

    Google Scholar 

  21. Cros S, Wright M, Morimoto M, Lataste H, Couzinier JP, Krikorian A: Experimental antitumor activity of navelbine. Semin Oncol 16(Suppl 4):15–20, 1989.

    Google Scholar 

  22. Besenval M, Delgado M, Demarez JP, Krikorian A: Safety and tolerance of navelbine in phase I and II studies. Semin Oncol 16(Suppl 4):37–40, 1989.

    Google Scholar 

  23. Dieras V, DeCremoux P, Extra JM, Leandri S, Delgado M, Espie M, Morvan F, Marty M: A 2 stage sequential phase II study of vinorelbine in patients with previously treated advanced breast cancer. Breast Cancer Res Treat 14:146, 1989 (abstract).

    Google Scholar 

  24. Toussaint G, Izzo J, Spielman M, Chabot G, May-Levin F, LeChevalier T, Turz T, Armano JP, Merles C, Cvitkovic E: A phase I-II study of navelbine by 96 hours continuous infusion in metastatic breast cancer. Breast Cancer Res Treat 19:169, 1991 (abstract).

    Google Scholar 

  25. Marty M, Extra JM, Dieras V, Giacchetti S, Ohana S, Espie M: A review of the antitumor activity of vinorelbine in breast cancer. Drugs 44(Suppl 4):29–35, 1992.

    Google Scholar 

  26. Canobbio L, Boccardo F, Pastorino G, Frema F, Martini C, Resasco M, Santi L: Phase II study of navelbine in advanced breast cancer. Semin Oncol 16(Suppl 4):33–36, 1989.

    Google Scholar 

  27. Tresca P, Fumoleau P, Roche H, Pinon G, Serin D, Marie FN, Delgado M, Belpomme D: Vinorelbine, a new active drug in breast carcinoma — results of an ARTAC phase II trial. Breast Cancer Res Treat 16:161, 1990 (abstract).

    Google Scholar 

  28. Fumoleau P, Delgado FM, Delozier T, Monnier A, Delgado MAG, Kerbrat P, Garcia-Giralt E, Keiling R, Namer M, Closon MT, Goudier MJ, Chollet P, Lecourt L, Montcuquet P, et al: Phase II trial of weekly intravenous vinorelbine in first line advanced breast cancer chemotherapy. J Clin Oncol 11:1245–1252, 1993.

    Google Scholar 

  29. Rowinsky E, Donehower R: The clinical pharmacology and use of antimicrotubular agents in cancer chemotherapeutics. Pharmac Ther 52:35–84, 1991.

    Google Scholar 

  30. Rao SX, Ramaswamy G, Levin M, McCravey JW: Fatal acute respiratory failure after vinblastine mitomycin therapy in lung carcinoma. Arch Intern Med 145:1905–1907, 1985.

    Google Scholar 

  31. Bott SJ, Stewart FM, Prince-Fiocco MA: Interstitial lung disease associated with vindesine and radiation therapy for carcinoma of the lung. South Med J 79:894–896, 1986.

    Google Scholar 

  32. Purvis J: Pulmonary reactions following navelbine administration. Burroughs Wellcome Co. Clinical Alert, May 1992.

  33. Cvitkovic E, Izzo J: The current and future place of vinorelbine in cancer therapy. Drugs 44(Suppl 2):36–45, 1992.

    Google Scholar 

  34. Mathe G, Ribaud P, Gouveia J:In Pierre Fabre, Internal report on navelbine, Part IV B, 2:38, 1988.

  35. Favre R, Serage J:In Pierre Fabre, Internal report on navelbine, Part IV B, 5:38, 1988

  36. Armand JP, Marty M: Navelbine — a new step in cancer therapy? Semin Oncol 16(Suppl 4):41–45, 1989.

    Google Scholar 

  37. Marty M, Leandri S, Extra JM, Espie M, Besemva M: A phase II trial of vinorelbine in patients with advanced breast cancer. Proc Am Assoc Cancer Res 30:256, 1989 (abstract).

    Google Scholar 

  38. Izzo J, Toussaint C, Chabot G, May-Levin F, LeChevalier T, Turz T, Riggi M, Armand JP, Merle S, Spielmann M, Cvitkovic E: High activity and dose intensity relationship in advanced breast cancer with continuous infusion of navelbine. Proc Am Soc Clin Oncol 11:71, 1992 (abstract).

    Google Scholar 

  39. Bruno S, Puerto Lima V, Texeira L, Milkiewicz E, Fernandez O, Martinez L, Delgado FM, Hegg R, Noguera C, Solidoro A, Otero J, Lecourt L, Delgado C: Phase II trial with vinorelbine in the treatment of advanced breast cancer. Proc 7th NCI-EORTC Symposium on New Drugs in Cancer Therapy, p 126, Amsterdam, 1992, (abstract).

  40. Lluch A, Garcia Conde J, Casado A, Martin M, Diaz Rubio E, Olivera C, Gervasio MH, DePablo JL, Garcia Giron JL, Gorostiaga J, Martinez A, Delgado FM: Phase II trial with navelbine in advanced breast cancer previously untreated. Proc Am Soc Clin Oncol 11:72, 1992 (abstract).

    Google Scholar 

  41. Romero A, Rabinovich M, Vallejo C, Perez J, Rodriguez R, Cuevas MA, Machiavelli M, Lacava J, Langhe M, Romero Acuna L, Amato S, Bardieri R, Leone B: Promising preliminary results of weekly navelbine as first line chemotherapy for metastatic breast cancer. Proc Am Soc Clin Oncol 12:76, 1993 (abstract).

    Google Scholar 

  42. Weber B, Vogel C, Jones S, Harvey H, Hutchins L, Purvis J, Hohneker J: A U.S. multicentered phase II trial of navelbine in advanced breast cancer. Proc Am Soc Clin Oncol 12:61, 1993 (abstract).

    Google Scholar 

  43. Brosio C, Cinat G, Michiewicz E, Cabalar M, Alvarez A, Piris N, Giglio R, Dodyk P, Andrade P, Ezcirdia L: Granulocyte colony stimulating factor support in weekly chemotherapy with vinorelbine. Proc Am Soc Clin Oncol 12:144, 1993 (abstract).

    Google Scholar 

  44. Spielman M, Dorval T, Turpin F: Phase II study with navelbine adriamycin combination in advanced breast cancer. Proc Am Soc Clin Oncol 10:66, 1991 (abstract).

    Google Scholar 

  45. Blajman C, Balbiani L, Block J, Bianchi R, Temperley G, Chacon R, Capo A, Cappola F, Bader MF, Giachella O, Gil Deza E, Almira E, Fein L, Lucero R, Alvarez A, Martinez J, Jaremtchuk A, Rosembrock C, Vilanova M, Gomez O, Zoricomba A, Mickiewicz E, Muro H, Reale M, Schmilovich A, Santarelli M: Navelbine plus adriamycin versus FAC in advanced breast cancer. Proc Am Soc Clin Oncol 12:92, 1993 (abstract).

    Google Scholar 

  46. Dieras V, Extra JM, Morsan F, Bellisant E, Espie M, Giachetti S, Bardi N, Marty M: Phase II study of navelbine and fluorouracil in metastatic breast cancer patients using a grouped sequential design. Proc 7th NCI/EORTC Symposium on New Drugs in Cancer Therapy, p 125, 1992 (abstract).

  47. Chadjaa M, Izzo J, May-Levin F, Riggi M, Cvitkovic E, Armano JP: Preliminary data on 4'-epiadriamycin — vinorelbine, a new active combination in advanced breast cancer. Proc Am Soc Clin Oncol 12:88, 1993 (abstract).

    Google Scholar 

  48. Giachetti S: Personal communication cited in: Marty M, Extra JM, Dieras V, Giacchetti S, Ohana S, Espie M: A review of the antitumor effect of vinorelbine in breast cancer. Drugs 44(Suppl 4):29–35, 1992.

    Google Scholar 

  49. Ferroro JM, Wendling JL, Hoch M, Frenay M, Francois E, Namer M: Mitoxantrone-vinorelbine as first line chemotherapy in metastatic breast cancer — a pilot study. Proc Am Soc Clin Oncol 12:108, 1993 (abstract).

    Google Scholar 

  50. VanPraagh I, Martineau N, Cure H, Lipinski F, Ravoux MA, Fleury J, Deloche C, Plagre R, Chollet PH: Efficacy of a chemotherapy regimen combining vinorelbine, epirubicin, and methotrexate in locally advanced and metastatic breast cancer. Proc Am Soc Clin Oncol 12:95, 1993 (abstract).

    Google Scholar 

  51. Bonneterre J, Pion JM, Adenis A, Tubiana-Hulin M, Tursz T, Marty M, Mathieu Boue A: A phase II study of a new camptothecin analogue CPT-11 in previously treated advanced breast cancer patients. Proc Am Soc Clin Oncol 12:94, 1993 (abstract).

    Google Scholar 

  52. Trudeau ME, Eisenhauer E, Lofters W, Norris B, Muldal A, Letendre F, Vandenberg T, Verma S: Phase II study of taxotere as first line chemotherapy for metastatic breast cancer. A National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) study. Proc Am Soc Clin Oncol 12:64, 1993 (abstract).

    Google Scholar 

  53. Scheithauer W, Dittrich Ch, Kornek G, Likesch W, Haider K, Depisch D: A phase II trial of amonafide in metastatic breast cancer. Proc Am Soc Clin Oncol 10:66, 1991 (abstract).

    Google Scholar 

  54. Vandenberg T, ten Bokkel Huinink W, Hedley D, Panasce LM, Verma S, Calvert H, Azarnia N, Francher D, Sisk R, Symes A: A phase II study of DUP941 in advanced breast cancer patients with no prior chemotherapy. Proc Am Soc Clin Oncol 12:67, 1993 (abstract).

    Google Scholar 

  55. Band PR, Maroun J, Pritchard K, Stewart D, Coppin CM, Wilson K, Eisenhauer EA: Phase II study of lonidamine in patients with metastatic breast cancer, a National Cancer Institute of Canada clinical trials group study. Cancer Treat Rep 70:1305–1310, 1986.

    Google Scholar 

  56. Hortobagyi GN: Overview of new treatments for breast cancer. Breast Cancer Res Treat 21:3–13, 1992.

    Google Scholar 

  57. Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Slim GA: Plant antitumor agents, 1. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor fromCamptotheca acuminata. J Am Chem Soc 88:3888–3890, 1966.

    Google Scholar 

  58. Gottlieb JA, Guarino AM, Call JB, Olivero VT, Block JB: Preliminary pharmacologic and clinical evaluation of camptothecin sodium (NSC 100880). Cancer Chemother Rep 54:461–470, 1970.

    Google Scholar 

  59. Muggia FM, Creaven PJ, Hansen H, Cohen MH, Selawry DS: Phase 1 clinical trial of weekly and daily treatment with camptothecin (NSC 100880). Correlation with preclinical studies. Cancer Chemother Rep 56:515–521, 1972.

    Google Scholar 

  60. Gottlieb JA, Luce JK: Treatment of malignant melanoma with camptothecin (NSC 100880). Cancer Chemother Rep 56:103–105, 1972.

    Google Scholar 

  61. Mortel CG, Schutt AJ, Reilemeier RJ, Hahn RG: Phase II study of camptothecin (NSC100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep 56:95–101, 1972.

    Google Scholar 

  62. Xu B, Chen J-T, Yang J-L, Chang S-Y, Yueh H-F, Wang T-W, Chou C-H: New results in pharmacologic research of some anticancer agents.In: Burns JJ, Tsuchitani PJ (eds) Proceedings of US-China Pharmacologic Symposium. Committee on Scholarly Communication with the Peoples Republic of China, National Academy of Sciences, Washington DC, 1979, pp 151–158.

    Google Scholar 

  63. Kingsbury WD, Boehm JC, Jakas DR, Holden KG, Hecht SM, Gallagher G, Caranaga MJ, McCabe FL, Faucette LF, Johnson RK, Herzberg RP: Synthesis of the water soluble (amino-alkyl) camptothecin analogues: inhibition of topoisomerase 1 and antitumor activity. J Med Chem 34:98–107, 1991.

    Google Scholar 

  64. Burris HA, Rothenberg ML, Kuhn JG, Von Hoff DD: Clinical trials with the topoisomerase 1 inhibitors. Semin Oncol 19:663–669, 1992.

    Google Scholar 

  65. Kunimoto T, Nitta K, Tanaka T, Kehara N, Baba H, Takeuche M, Yokokura T, Sawaoa S, Miyasaka T, Mutai M: Antitumor activity of 7-ethyl-10-(4-(1-piperidino)-1-piperidino)carbonyloxy camptothecin, a novel water soluble derivative of camptothecin, against murine tumors. Cancer Res 47:5944–5947, 1987.

    Google Scholar 

  66. Slichenmyer WJ, Rowinsky EK, Donehower RC, Kaufmann SH: The current status of camptothecin analogues as antitumor agents. J Natl Cancer Inst 85:271–291, 1993.

    Google Scholar 

  67. Horwitz SB, Horwitz MS: Effects of camptothecin on the breakage and repair of DNA during the cell cycle. Cancer Res 33:2834–2836, 1973.

    Google Scholar 

  68. Sparato A, Kessel D: The effects of camptothecin on mammalian DNA. Biochem Biophys Acta 331:194–201, 1973.

    Google Scholar 

  69. Tsao YP, D'Arpa P, Liu L: The involvement of active DNA synthesis in camptothecin-induced G2 arrest: altered regulation of p34cdc2/cyclin B1. Cancer Res 52:1823–1829, 1992.

    Google Scholar 

  70. McSheehy PM, Gervasoni M, Lampasona V, Erba E, D'Incalci M: Studies of the differentiation properties of camptothecin in the human leukemic cells K562. Eur J Cancer 27:1406–1411, 1991.

    Google Scholar 

  71. Hendricks CB, Rowinsky EK, Grochow LB, Donehower RC, Kaufmann SH: Effects of P-glycoprotein expression on accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res 52:2268–2278, 1992.

    Google Scholar 

  72. Niimi S, Nakagawa K, Sugimoto Y, Nishio K, Fujiwara Y, Yokoyama S, Terashima Y, Saijo N: Mechanisms of cross resistance to a camptothecin analogue (CPT-11) in a human ovarian cancer cell line selected by cisplatin. Cancer Res 52:328–333, 1992.

    Google Scholar 

  73. Sugimoto Y, Tsukahara S, Oh-Hara T, Isoe T, Tsunio T: Decreased expression of DNA topoisomerase 1 in camptothecin resistant tumor cell lines as determined by monoclonal antibody. Cancer Res 50:6925–6930, 1990.

    Google Scholar 

  74. Grochow LB, Rowinsky EK, Johnson R, Ludeman S, Kaufmann SH, McCabe FL, Smith BR, Hurowitz L, DeLisa A, Donehower RC, Noe DA: Pharmacokinetics and pharmacodynamics of topotecan in patients with advanced cancer. Drug Metab Dispos 20:706–713, 1992.

    Google Scholar 

  75. Rothenberg MK, Kuhn J, Burris HA, Morales MT, Nelson J, Eckardt JR, Rock MK, Terada K, Von Hoff DD: A phase 1 and pharmacokinetic trial of CPT-11 in patients with refractory solid tumors. Proc Am Soc Clin Oncol 11:113, 1992 (abstract).

    Google Scholar 

  76. Chabot CG, Abigerges D, Gandia D, Armand JP, Clavel M, De Forni M, Suc E, Bugat R, Culine S, Extra JM, Marty M, Mathieu Boue A, Gouyette A: Pharmaco-kinetic-pharmacodynamic relationships in patients administered with CPT-11, a new camptothecin analogue. Proc Am Assoc Cancer Res 33:266, 1992 (abstract).

    Google Scholar 

  77. Kaneda N, Yokokura T: Non linear pharmacokinetics of CPT-11 in rats. Cancer Res 50:1721–1725, 1990.

    Google Scholar 

  78. Sasaki Y, Morita M, Miya T, Shinkai T, Eguchi K, Tamura T, Ohe Y, Saijo N: Pharmacokinetics and pharmacodynamic analysis of CPT-11 and its active metabolite SN38. Proc Am Soc Clin Oncol 11:111, 1992 (abstract).

    Google Scholar 

  79. Burris HA III, Hanauske AR, Johnson RK, Marshall MH, Kuhn JG, Hilsenbeck SG, Von Hoff DD: Activity of topotecan, a new topoisomerase 1 inhibitor, against human tumor colony forming units in vitro. J Natl Cancer Inst 84:1816–1820, 1992.

    Google Scholar 

  80. Houghton PJ, Cheshire PJ, Myers L, Houghton JA: Evaluation of 9-dimethylaminomethyl-10-hydroxy camptothecin (topotecan) against xenografts derived from adult and child hood tumors.In Proc 7th NCIEORTC Symposium on New Drugs in Cancer Therapy, Amsterdam, 1992, p 84 (abstract).

  81. Kawato Y, Furuta T, Aonuma M, Yashoka M, Yokokura T, Matsumoto K: Antitumor activity of a camptothecin derivative CPT-11 against human tumor xenografts in nude mice. Cancer Chemother Pharmacol 28:192–198, 1991.

    Google Scholar 

  82. Pantazis P, Early JA, Kozielshi AJ, Mendoza JT, Hinz HR, Giovanella BC: Regression of human breast carcinoma tumors in immunodeficient mice treated with 9-nitrocamptothecin: differential response of nontumorigenic and tumorigenic human breast cells in vitro. Cancer Res 53:1577–1582, 1993.

    Google Scholar 

  83. Murphy B, Saltz L, Sirott M, Young C, Tong B, Trochanowski B, Toomasi F, Kelsen D: Granulocyte colony stimulating factor does not increase the maximum tolerated dose in a phase 1 study of topotecan. Proc Am Soc Clin Oncol 11:139, 1992 (abstract).

    Google Scholar 

  84. Rowinsky EK, Sartorius S, Grochow L, Forastiere A, Lubejko B, Hurowitz L, Donehower R: Phase 1 and pharmacologic study of topotecan, an inhibitor of topoisomerase 1, with granulocyte colony stimulating factor. Toxicologic differences between concurrent and post treatment G-CSF administration. Proc Am Soc Clin Oncol 11:116, 1992 (abstract).

    Google Scholar 

  85. Janik J, Miller L, Smith J, Kopp W, Alvord G, Gause B, Curti B, Urba WJ, Longo DL: Prechemotherapy granulocyte macrophage colony stimulating factor prevents topotecan induced neutropenia. Proc Am Soc Clin Oncol 12:437, 1993 (abstract).

    Google Scholar 

  86. Rowinsky E, Grochow L, Ettinger D, Hendricks C, Lubejko B, Sartorius S, Hurowitz L, McGuire W, Rock M, Donehower R: Phase 1 and pharmacologic study of CPT-11, a semisynthetic topoisomerase 1 targeting agent, on a single dose schedule. Proc Am Soc Clin Oncol 11:115, 1992 (abstract).

    Google Scholar 

  87. Ohno R, Okada K, Masoaka T, Kuramoto A, Arima T, Yoshida Y, Ariyoshi H, Ichimani M, Sakei Y, Oguro M, Ito Y, Morishina Y, Yokomaku S, Ota K: An early phase II study of CPT-11, a new derivative of camptothecin, for the treatment of leukemia and lymphoma. J Clin Oncol 8:1225–1229, 1990.

    Google Scholar 

  88. Negoro S, Fukuoka M, Masuda N, Takada M, Kusunoki Y, Matsui K, Takitugi N, Kudoh S, Niitani H, Taguchi T: Phase 1 study of a weekly infusion of CPT-11, a new derivative of camptothecin, in the treatment of advanced nonsmall cell lung cancer. J Natl Cancer Inst 83:1164–1168, 1991.

    Google Scholar 

  89. Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M: CPT-11, a new derivative of camptothecin for the treatment of refractory or relapsed small cell lung cancer. J Clin Oncol 10:1225–1229, 1992.

    Google Scholar 

  90. Hochster H, Speyer J, Orutz R, Meyers M, Wernz J, Chachoua A, Raphael B, Lee R, Sorich J, Taubes B, Liebes L, Fry D, Blum R: Topotecan 21 day continuous infusion — excellent tolerance on a novel schedule. Proc Am Soc Clin Oncol 12:139, 1993 (abstract).

    Google Scholar 

  91. Clavel M, Mathieu-Boue A, Dumortier A, Chabot GG, Cole C, Bissery MC, Marty M: Phase 1 study of CPT-11 administered as a daily infusion for 3 consecutive days. Proc Am Assoc Cancer Res 33:262, 1992 (abstract).

    Google Scholar 

  92. Mattern MR, Hoffman GA, McCabe FL, Johnson RK: Synergistic cell killing by ionizing radiation and topoisomerase 1 inhibitor SK&F 104864. Proc Am Assoc Cancer Res 31:436, 1990 (abstract).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

O'Reilly, S., Kennedy, M.J., Rowinsky, E.K. et al. Vinorelbine and the topoisomerase 1 inhibitors: Current and potential roles in breast cancer chemotherapy. Breast Cancer Res Tr 33, 1–17 (1995). https://doi.org/10.1007/BF00666066

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00666066

Key words

Navigation