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Neurological toxicity of vindesine used in combination chemotherapy of 51 human solid tumors

  • Original Articles
  • Vindesine Neurotoxicity
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Summary

The authors treated 51 patients with solid tumours with vindesine 4 mg/m2, generally every third week, in combination chemotherapy protocols scheduled according to diurnal variability of kinetics.

No dose-related sensory disorders were observed: On the contrary, motor toxicity appeared cumulative:

  1. 1)

    Early depression of osteotendinous reflexes from the first course onward, with progressive deterioration. No more normal reflexes could be evoked after 55 mg;

  2. 2)

    Early appearance of neurogenic pattern in the electromyograph after 5–10 mg. Progressive alteration with no normal detection recordings after 45 mg;

  3. 3)

    Late slowing down of conduction speeds (normal in 50% of cases up to 55–60 mg).

Improvement or even complete recovery of neuropathy was documented following reduction of the unit dose, increased time interval between doses, or discontinuation of the treatment. The drug had to be withheld in only three patients: in two cases a low dosage related to individual sensitivity was being used.

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References

  1. Barnett CJ, Cullinan GJ, Gerzon K, Hoying RC, Jones WE, Newlon WM, Poore GA, Robinson RL, Sweeney MJ, Todd GC (1978) Structure activity relationships of dimeric catharanthus alkaloids. 1. Deacetyl-vinblastine amide (vindesine) sulfate. J Med Chem 21:88–96

    Google Scholar 

  2. Bodey GP, Valdivieso M, Bedikian AY, Yap BS, Burgess A (1980a) Vindesine in patients with solid tumors and acute leukemias. Internationales Vinca-Alkaloid-Symposium: Eldisine (Vindesin), Frankfurt/Main, November 1980 (Abstract 12)

  3. Bodey GP, Yap HY, Blumenschein GR, Hortobagyi GN, Buzdar AU (1980b) Continuous infusion of vinca alkaloids in breast carcinoma. Internationales Vinca-Alkaloid-Symposium: Eldisine (Vindesin), Frankfurt/Main, November 1980 (Abstract 28)

  4. Bonadonna G, Zucali R, De Lena M, Valagussa P (1977) Combined chemotherapy (MOPP or ABVD)-radiotherapy approach in advanced Hodgkin's disease. Cancer Treat Rev 61:769–777

    Google Scholar 

  5. Bradley WG (1970) The neuromyopathy of vincristine in the guinea pig. An electrophysiological and pathological study. J Neurol Sci 10:133–162

    Google Scholar 

  6. Bradley WG, Lassman LP, Pearce GW, Walton JN (1970) The neuromyopathy of vincristine in man. Clinical, electrophysiological and pathological studies. J Neurol Sci 10:107–131

    Article  CAS  PubMed  Google Scholar 

  7. Casey EB, Jelliffe AM, Lequesne PM, Millett YL (1973) Vincristine neuropathy: clinical and electrophysiological observations. Brain 96:69–86

    CAS  PubMed  Google Scholar 

  8. De Vita VT Jr, Serpick AA, Carbone PP (1970) combination chemotherapy in the treatment of advanced Hodgkin's disease. Ann Intern Med 73:881–895

    Google Scholar 

  9. Dyke RW, Nelson RL (1977) Phase I anti-cancer agent: vindesine (desacetyl vinblastine amide sulfate). Cancer Treat Rev 4:135–142

    Google Scholar 

  10. Dyke RW, Nelson RL, Brade WP (1979) Vindesine — A short review of preclinical and first clinical data. Cancer Chemother Pharmacol 2:229–232

    Google Scholar 

  11. Einhorn LH, Furnas B (1977) Improved chemotherapy in disseminated testicular cancer. J Clin Hematol Oncol 7:662–671

    Google Scholar 

  12. Focan C (1975) Chimiothérapie séquentielle basée sur l'hypothèse d'un rythme circadien de la prolifération tumorale. Nouv Presse Med 4:2709–2712

    Google Scholar 

  13. Focan C (1979) Sequential chemotherapy and circadian rhythm in human solid tumours. A randomized trial. Cancer Chemother Pharmacol 3:197–202

    Google Scholar 

  14. Focan C (1980) Circadian rhythm and sequential combination chemotherapy for advanced lung cancer. Comparative interest of vinblastine versus vindesine. Abstracts of the 2nd World Conference on Lung Cancer, Copenhagen, June 1980, p 228

  15. Focan C, Barbason H, Betz EH (1973a) Influence du rythme nycthéméral des divisions cellulaires sur l'efficacité de la cyclophosphamide contre des sarcomes produits par le méthylcholanthrène. C R Acad Sci [D] (Paris) 276:2105–2108

    Google Scholar 

  16. Focan C, Barbason H, Betz EH (1973b) Mise en évidence d'un rythme nycthéméral de la division cellulaire dans des sarcomes induits par le méthylcholanthrene. C R Acad Sci [D] (Paris) 276:2229–2332

    Google Scholar 

  17. Focan C, Bricteux N, Lemaire M, Hugues J (1975a) La polychimiothérapie dans le traitement des lymphopathies malignes à un stade avancé. Rev Med Liege 30:406–411

    Google Scholar 

  18. Focan C, Barbason H, Betz EH (1975b) Use of synchronization induced by cyclophosphamide in a methylcholanthrene sarcoma with circadian proliferation to rational sequential chemotherapy. Biomedicine [Express] 23:230–235

    Google Scholar 

  19. Focan C, Le Hung S, Claessens JJ, Debruyne H (1979a) Inclusion of vindesine in sequential chemotherapy based upon the circadian rhythm of human solid tumors. J Cancer Res Clin Oncol 95:99–100

    Google Scholar 

  20. Focan C, Olivier R, Le Hung S, Bays R (1979b) Vindesine-induced neuropathy. A clinical and electro-physiological study in 51 human solid tumors. Medical oncology. Abstracts of the 5th Annual Meeting of the Medical Oncology Society, Nice, December 1979, p 20 (Abstract 79)

  21. Ginsberg SJ, Comis RL, Fitzpatrick AV (1977) Vinblastine and inappropriate ADH secretion. N Engl J Med 296:941

    Google Scholar 

  22. Gottschalk G, Dyck PJ, Kiely JM (1968) Vinca alkaloid neuropathy: nerve biopsy studies in rats and in man. Neurology 18:875–882

    Google Scholar 

  23. Gralla RJ, Casper ES, Kelsen DP, Golbey RB (1980) Vindesine and cisplatin combination chemotherapy in non-small cell lung cancer: a two-year follow-up. Abstracts of the 2nd World Conference on Lung Cancer, Copenhagen, June 1980, p 229

  24. Hildebrand J, Kenis Y (1971) Additive toxicity of vincristine and other drugs for the peripheral nervous system. Acta Neurol Belg 71:486–491

    Google Scholar 

  25. Hildebrand J, Kenis Y (1972) Vincristine neurotoxicity. N Engl J Med 287:517

    Google Scholar 

  26. Holsti LR, Mattson K, Grohn P, Heinonen E, Saastamoinen M (1980) Combination chemotherapy with cis-platinum, VP-16 and vindesine in non-small cell lung cancer. Abstracts of the 2nd World Conference on Lung Cancer, Copenhagen, June 1980, p 231

  27. Hoogstraten B, Owens AH, Lenhard RE, Glidewell OJ, Leone LA, Orson KB, Harley JB, Townsend SR, Miller SP, Spurr CL (1969) Combination chemotherapy in lymphosarcoma and reticulum cell sarcoma. Blood 33:370–378

    Google Scholar 

  28. Jelliffe AM (1968) Peripheral nerve damage with vincristine sulfate. In: Shedden-Altrinchan WIH (ed) The vinca alkaloids in the chemotherapy of malignant disease. Sherratt, London, p 91

    Google Scholar 

  29. Kleinknecht D, Jacquillat C, Weil M, Najean Y, Tanzer J, Boiron M, Bernard J (1967) Les accidents neurologiques centraux de la vincristine. Nouv Rev Fr Hematol 7:132–136

    Google Scholar 

  30. Levitt LP, Prager D (1975) Mononeuropathy due to vincristine toxicity. Neurology 25:894–895

    Google Scholar 

  31. Livingston RB, Fee WH, Einhorn LH, Burgess MA, Freireich EJ, Gottlieb JA, Farber MO (1976) Bacon (bleomycin, adriamycin, CCNU, Oncovin, and nitrogen mustard) in squamous lung cancer. Experience in fifty patients. Cancer 37:1237–1242

    Google Scholar 

  32. Mathé G, Misset JL, de Vassal F, Hayat M, Gouveia J, Machover D, Belpomme D, Schwarzenberg L, Ribaud P, Pico JM, Musset M, Jasmin C, De Luca L (1978) Traitement de leucémies et hématosarcomes par la vindésine. Résultats d'un essai phase II en termes d'induction de rémission. Nouv Presse Med 7:525–528

    Google Scholar 

  33. Mattson K, Holsti LR, Grohn P, Salmo M, Saastamoinen M, Heinonen E (1980) Experience with vindesine in the treatment of lung cancer. Abstracts of the 2nd World Conference on Lung Cancer, Copenhagen, June 1980, p 234

  34. Misset JL, Mathé G, de Vassal F, Delgado M, Musset M, Metral S (1980) Long-term administration of vindesine in maintenance regimen for poor prognosis acute lymphoblastic leukemia (ALL). Apparent lack of long term cumulative neurotoxicity. Internationales Vinca-Alkaloid-Symposium: Eldisine (Vindesin). Frankfurt/Main, November 1980 (Abstract 14)

  35. Moress GR, D'Agostino AN, Jarcho LW (1967) Neuropathy in lymphoblastic leukemia treated with vincristine. Arch Neurol 16:377–384

    Google Scholar 

  36. Mubashir BA, Bart JB (1972) Vincristine neurotoxicity. N Engl J Med 287:517

    Google Scholar 

  37. Natale RB, Gralla RJ, Wittes RE (1980) Phase II trials of vindesine (DVA), AMSA, and PCNU in patients with small cell lung cancer. Abstracts of the 2nd World Conference on Lung Cancer, Copenhagen, June 1980, p 235

  38. Nelson RL, Dyke RW, Root MA (1979) Clinical pharmaco-kinetics of vindesine. Cancer Chemother Pharmacol 2:243–246

    Google Scholar 

  39. Obrist R, Paravicini U, Hartmann D, Nagel LA, Obrecht JP (1979) Vindesine. A clinical trial with special reference to neurological side effects. Cancer Chemother Pharmacol 2:233–237

    Google Scholar 

  40. Owellen RJ, Hartke CA, Hains FO (1977a) Pharmacokinetics and metabolism of vinblastine in humans. Cancer Res 37:2597–2602

    Google Scholar 

  41. Owellen RJ, Root MA, Hains FO (1977b) Pharmacokinetics of vindesine and vincristine in humans. Cancer Res 37:2603–2607

    Google Scholar 

  42. Philip T, Souillet G, Gharib C, Geelen G, Allevard AM, Hartemann E, David M (1979) Secrétion inappropriée d'hormone antidiurétique au cours de leucémies aiguës traitées par vincristine. Nouv Presse Méd 8:2181–2185

    Google Scholar 

  43. Pinedo HM, Voute PA (1977) Combination chemotherapy in soft tissue sarcomas. In: Tagnon HJ, Staquet MJ (eds) Recent advances in cancer treatment. Raven Press, New York, p 301–310

    Google Scholar 

  44. Price LA, Hill BT, Dalley CM (1978) Improved results in combination chemotherapy of head and neck cancer using a kinetically-based approach: a randomized study with and without Adriamycin. Oncology 35:26–28

    Google Scholar 

  45. Retsas S, Newton KA, Westbury G (1979) Evaluation of vindesine in advanced malignant melanoma. A phase II study. In: Wild RN (ed) Proceedings of the Sixth Vinca Alkaloid Symposium: Vindesine. pp 37–45

  46. Robertson GL, Bhoopalam N, Zelkonitz LJ (1973) Vincristine neurotoxicity and abnormal secretion of antidiuretic hormone. Arch Intern Med 132:717–720

    Google Scholar 

  47. Rosenthal S, Kaufman S (1974) Vincristine neurotoxicity. Ann Intern Med 80:733–737

    Google Scholar 

  48. Sanderson PA, Kuwabara T, Cogan DG (1976) Optic neuropathy presumably caused by vincristine therapy. Am J Ophthalmol 81:146–150

    Google Scholar 

  49. Sandler SG, Tobin W, Henderson ES (1969) Vincristine-induced neuropathy. A clinical study of fifty leukemic patients. Neurology 19:367–374

    CAS  PubMed  Google Scholar 

  50. Slater LM, Wainer RA, Serpick AA (1969) Vincristine neurotoxicity with hyponatremia. Cancer 23:122–125

    Google Scholar 

  51. Smith IE, Hedley DW, Powles TJ, McElwain TJ (1979) Clinical experience with vindesine in sixty patients with solid tumors. In: Wild RN (ed) Proceedings of the Sixth Vinca Alkaloid Symposium: Vindesine. pp 11–16

  52. Tobin WE, Sandler SG (1968) Neurophysiologic alterations induced by vincristine (NSC-67574). Cancer Chemother Rep 52:519–526

    Google Scholar 

  53. Todd GC, Griffing WJ, Gibson WR, Morton DM (1979) Animal models for the comparative assessment of neurotoxicity following repeated administration of vinca alkaloids. Cancer Treat Rep 63:35–41

    Google Scholar 

  54. Uy QL, Moen TH, Johns RJ, Owens AH (1967) Vincristine neurotoxicity in rodents. Johns Hopkins Med J 121:349–360

    Google Scholar 

  55. Walton JN (1974) Disorders of voluntary muscle, 3rd edn. Churchill Livingstone, London, pp 973–1033

    Google Scholar 

  56. Watkins SM, Griffin JP (1978) High incidence of vincristine-induced neuropathy in lymphomas. Br Med J 1:610–612

    Google Scholar 

  57. Weber W, Tackmann W, Ludwig C, Egger R, Obrecht JP (1980) Vindesine 24-h infusion. Phase I study. Internationales Vinca-Alkaloid-Symposium: Eldisine (Vindesine), Frankfurt/Main, November 1980 (Abstract 10)

  58. Weiss HD, Walker MD, Wiernik PH (1974a) Neurotoxicity of commonly used antineoplastic agents (1). N Engl J Med 291:75–81

    Google Scholar 

  59. Weiss HD, Walker MD, Wiernik PH (1974b) Neurotoxicity of commonly used antineoplastic agents (2). N Engl J Med 291:127–133

    CAS  PubMed  Google Scholar 

  60. Zelen M (1973) Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 4:31–42

    Google Scholar 

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Focan, C., Olivier, R., Hung, S.L. et al. Neurological toxicity of vindesine used in combination chemotherapy of 51 human solid tumors. Cancer Chemother. Pharmacol. 6, 175–181 (1981). https://doi.org/10.1007/BF00262339

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