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Paclitaxel neurotoxicity: clinical and neurophysiological study of 23 patients

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Abstract

Paclitaxel is the prototype of a new class of chemotherapeutic agents with an antimitotic effect that is related to its ability to interfere with the microtubule system. It causes peripheral neurological toxicity by means of its activity on the axonal microtubules.

To define the clinical and neurophysiological characteristics of paclitaxel neuropathy 23 patients undergoing paclitaxel therapy at a dose of 175 mg/m2 were studied. The patients were divided into two groups, with only one group receiving pretreatment with potentially neurotoxic drugs such as cisplatin and carboplatin. The results showed a high incidence of mild neurotoxicity in both groups. Treatment was discontinued due to severe neurotoxicity in only one patient pretreated with platinum-compounds. The clinical and neurophysiological data make it possible to define paclitaxel neurotoxicity as a distal axonal neuropathy with a summatory effect in patients pretreated with cisplatin; the possible reversibility of paclitaxel neurotoxicity requires further confirmation.

Sommario

Il Paclitaxel appartiene a una nuova categoria di farmaci antiblastici la cui attività è legata alla capacità di interferire con il sistema dei microtubuli.

La neurotossicità periferica è dovuta all'interferenza con i microtubuli assonali e all'alterazione del trasporto assonale.

Allo scopo di definire le caratteristiche cliniche e neurofisiologiche di questa neuropatia sono stati studiati 23 pazienti sottoposti a terapia con Paclitaxel al dosaggio di 175 mg/mq. I risultati dello studio hanno mostrato un'elevata incidenza di neurotossicità periferica di grado moderato, valutata con una scala di neurotossicità basata sui segni e sintomi clinici e sui dati neurofisiologici. L'insieme dei dati permette di definire la neuropatia da Paclitaxel come una neuropatia sensitivo-motoria distale di tipo assonale, la cui reversibilità richiede ulteriori conferme.

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References

  1. Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR.Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol, 1994; 35: 304–311.

    Article  PubMed  CAS  Google Scholar 

  2. Dyck PJ, Sherman WR, Hallcher LM.Human diabetic endoneurial sorbitol, fructose and myo-inositol related to sural nerve morphometry. Ann Neurol, 1980; 8: 590–596.

    Article  PubMed  CAS  Google Scholar 

  3. Donehower RC, Rowinsky EK, Grochow LB, Longnecker SL, Ettinger S.Phase I trial of taxol in patients with advanced cancer. Cancer Treat Rep, 1987; 71: 1171–1177.

    PubMed  CAS  Google Scholar 

  4. Donehower RC, Rowinsky EK.An overview of experience with taxol in the U.S.A. Cancer Treat Rev, 1993; 19: 63–78.

    Article  PubMed  Google Scholar 

  5. Einzig AL, Wiernik PH, Sasloff J, Runowicz CD, Goldberg GL.Phase II study and long-term follow-up of patients treated with taxol for advanced ovarian adenocarcinoma. J Clin Oncol, 1992; 10: 1748–1753.

    PubMed  CAS  Google Scholar 

  6. Ettinger DS.Overview of Paclitaxel (taxol) in advanced lung cancer. Sem Oncol, 1993; 20 (3): 46–49.

    CAS  Google Scholar 

  7. Forastiere AA.Use of Paclitaxel (taxol) in squamous cell carcinoma of the head and neck. Sem Oncol, 1993; 20(3): 56–60.

    CAS  Google Scholar 

  8. Hamers FPT, Gispen WH, Neijt JP.Neurotoxic side effects of cisplatin. Eur J Cancer, 1991; 27(3): 372–376.

    Article  PubMed  CAS  Google Scholar 

  9. Krarup-Hansen A, Fuglehom K, Helweg-Larsen S. et al.Examination of distal involvement in cisplatin- induced neuropathy in man. Brain, 1993; 116: 1017–1041.

    PubMed  Google Scholar 

  10. Lipton RB, Apfel SC, Dutcher JP.Taxol produces a predominantly sensory neuropathy. Neurology, 1989; 39: 368–373.

    PubMed  CAS  Google Scholar 

  11. McGuire WP, Rowinsky EK, Rosenshein NB. et al.Taxol: A unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasm. Ann Inter Med, 1988; 111: 273–279.

    Google Scholar 

  12. Mollman JE, Hogan WM, Glover DJ, McCluskey LF.Unusual presentation of cisplatinum neuropathy. Neurology, 1988; 38: 488–490.

    PubMed  CAS  Google Scholar 

  13. Mollman JE.Cisplatin neurotoxicity. N Engl J Med, 1990; 332, 2: 126–127.

    Article  Google Scholar 

  14. Murphy WK, Fossella FV, Winn RJ.Phase II study of taxol in patients with untreated non-small cell lung cancer. J Natl Cancer Inst, 1993; 85: 384–388.

    PubMed  CAS  Google Scholar 

  15. Oken MM.Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol, 1982; 5: 649–655.

    PubMed  CAS  Google Scholar 

  16. Pace A, Bove L, Pietrangeli A, Innocenti P, Jandolo B.Docetaxel neuropathy. Neurology, 1996; 47 (Letter): 615.

    PubMed  CAS  Google Scholar 

  17. Pietrangeli A, Pace A, Jandolo B.Neuropatia da Cisplatino. Riv Neurobiologia, 1990; 36 (1): 13–17.

    Google Scholar 

  18. Postma TJ, Vermorken JB, Liefting AJM, Pinedo HM, Heimans JJ.Paclitaxel induced neuropathy. Ann Oncol, 1995; 6: 489–494.

    PubMed  CAS  Google Scholar 

  19. Rowinsky EK, Cazenave LA, Donehower RC.Taxol: a novel investigational antimicrotubule agent. JNCI, 1990; 82: 1247–1259.

    PubMed  CAS  Google Scholar 

  20. Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC.Clinical toxicities encountered with paclitaxel (TAXOL). Sem Oncol, 1993; 20, 4(3): 1–15.

    CAS  Google Scholar 

  21. Rowinsky EK, Chaudhry V, Forastiere A. et al.Phase I and pharmacologic study of Paxlitaxel and cisplatin with granulocyte colony- stimulating factor: Neuromuscular toxicity is dose-limiting. J Clin Oncol, 1993; 11, 10: 2010–2020.

    PubMed  CAS  Google Scholar 

  22. Sarosy G, Kohn E, Stone DA. et al.Phase I study of Taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer. J Clin Oncol, 1992; 10: 1165–1170.

    PubMed  CAS  Google Scholar 

  23. Schaumburg HH, Spencer PS.Toxic neuropathies. Neurology, 1978; 29: 429–431.

    Google Scholar 

  24. Schiff PB, Fant J, Horwitz SB.Promotion of microtubule assembly in vitro by Taxol. Nature, 1979; 22: 665–667.

    Article  Google Scholar 

  25. Seidman AD, Norton L, Reichman BS.Preliminary experience with Paclitaxel (taxol) plus recombinant human granulocyte colony-stimulating factor in the treatment of breast cancer. Sem Oncol, 1993; 20(3): 40–45.

    CAS  Google Scholar 

  26. Swash M, Schwarz MS.Neuromuscular Disease, Chapter 7, Springer Verlag, Berlin, 1988: 113–123.

    Google Scholar 

  27. Swenerton K, Eisenhauer EA, ten Bokkel Huinink W. et al.Taxol in relapsed ovarian cancer: high vs low doses and short vs long infusion: A European-Canadian study coordinated by NCI Canada Clinical Trials Groups. Proc Am Soc Clin Oncol, 1993; 12: 256.

    Google Scholar 

  28. Thompson SW, Davis LE, Kornfeld M, Hilgers, Standefer JC.Cisplatin neuropathy: Clinical, Electrophysiologic, morphologic and toxicologic studies. Cancer, 1984; 54: 1269–1275.

    PubMed  CAS  Google Scholar 

  29. Vuorinen VS, Roytta M.Taxol-induced neuropathy after nerve crush: long-term effects on Schwann and endoneurial cells. Acta Neuropathol, 1990; 79: 653–662.

    Article  PubMed  CAS  Google Scholar 

  30. Vuorinen VS, Roytta M.Taxol-induced neuropathy after nerve crush: long-term effects on regenerating axons. Acta Neuropathol, 1990; 79: 663–667.

    Article  PubMed  CAS  Google Scholar 

  31. WHOHandbook for reporting results of cancer treatment, WHO offset Publication N. 48, Ginevra.

  32. Wiernick PH, Schwartz EL, Strauman JJ, Dutcher JP, Lipton RB andElisabeth Paietta.Phase I clinical and pharmacokinetic study of Taxol. Cancer Res, 1987; 47: 2486–2493.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Servizio di Neurologia, Istituto Nazionale Regina Elena per lo studio e la cura dei Tumori, Roma, Italy

    Pace A., Bove L., Pietrangeli A., Innocenti P. & Jandolo B.

  2. Divisione di Oncologia Medica, Istituto Nazionale Regina Elena per lo studio e la cura dei Tumori, Roma, Italy

    Aloe A., Nardi M. & Calabresi F.

Authors
  1. Pace A.
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  2. Bove L.
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  3. Aloe A.
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  4. Nardi M.
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  5. Pietrangeli A.
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  6. Calabresi F.
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  7. Innocenti P.
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  8. Jandolo B.
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Additional information

The study was supported in part by Italian National Research Council (CNR) grant 9400985CT04.

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Pace, A., Bove, L., Aloe, A. et al. Paclitaxel neurotoxicity: clinical and neurophysiological study of 23 patients. Ital J Neuro Sci 18, 73–79 (1997). https://doi.org/10.1007/BF01999566

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  • DOI: https://doi.org/10.1007/BF01999566

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