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Treatment and care of neurotoxicity from taxane anticancer agents

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Abstract

Taxane anticancer agents play a central role in drug therapy for breast cancer today; however, they have a dose-limiting neurotoxicity that is difficult to prevent and treat. To protect against this neurotoxicity it is important to avoid large doses greater than 200 mg/m2, and to adopt 24-hour administration regimens. Care is also needed with regard to the cumulative dose. Glutamine and amitriptyline are two of the very few drugs that have been found to be clinically effective against drug-induced peripheral neuropathy. Drugs are discontinued if neuropathy appears. If administration is to be later restarted, it is recommended that combined use of glutamine or amitriptyline be considered and that patients be given guidance for daily life.

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Abbreviations

NGF:

Nerve growth factor

ACTH:

Adrenocorticotropic hormone

IGF-I:

Insulin-like growth factor-l

SNCV:

Sensory nerve conduction velocity

ADL:

Activities of daily living

TENS:

Transcutaneouselectric nerve stimulation

References

  1. Rowinsky EK, Donehower RC: Paclitaxel (Taxol).New Engl J Med 332:1004–1014, 1995.

    Article  PubMed  CAS  Google Scholar 

  2. Ravdin PM, Valero V: Review of docetaxel (taxotere), a highly active new agent for the treatment of metastatic breast cancer.Semin Oncol 22:17–21, 1995.

    PubMed  CAS  Google Scholar 

  3. Fossella FV, Lee JS, Berille J, Hong WH: Summary of phase II data of docetaxel (taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer.Semin Oncol 22:22–29, 1995.

    PubMed  CAS  Google Scholar 

  4. Kaye SB: Docetaxel (taxotere) in the treatment of solid tumors other than breast and lung cancer.Semin Oncol 22:30–33, 1995.

    PubMed  CAS  Google Scholar 

  5. Gianni L, Capri G: New chemotherapy drugs. In: Bonadonna G, Hortobagyi GN, Gianni AM eds, Textbook of Breast Cancer — A Clinical Guide to Therapy, Martin Dunitz Ltd, London, pp253–280, 1997.

    Google Scholar 

  6. Rowinsky EK, Chaudhry V, Forastiere AA, Sartorius SE, Ettinger DS, Grochow LB, Lubejko BG, Cornblath DR, Donehower RC: Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: Neuromuscular toxicity is dose-limiting.J Clin Oncol 11:2010–2020, 1993.

    PubMed  CAS  Google Scholar 

  7. Sarosy G, Kohn E, Stone DA, Rothenberg M, Jacob J, Adamo DO, Ognibene FP, Cunnion R, Reed E: Phase I study of taxol and colony-stimulating factor in patients with refractory ovarian cancer.J Clin Oncol 10:1165–1170, 1992.

    PubMed  CAS  Google Scholar 

  8. Quasthoff S, Hartung HP: Chemotherapy-induced peripheral neuropathy.J Neurol 249:9–17, 2002.

    Article  PubMed  CAS  Google Scholar 

  9. Rowinsky EK, Chaudhry V, Cornblath DR, Donehower RC: Neurotoxicity of taxol.Monogr Natl Cancer Inst 15:107–115, 1993.

    PubMed  Google Scholar 

  10. van Gerven JMA, Moll JWB, van den Bent MJ, Bontenbal M, van der Burg MEL, Verwij J, Vecht ChJ: Paclitaxel (taxol) induces cumulative mild neurotoxicity.Eur J Cancer 30A:1074–1077, 1994.

    Article  PubMed  Google Scholar 

  11. Hilkens PH, Verweij JV, Stoter G, Vecht CJ, van Putten WL, van den Bent: Peripheral neuropathy induced by docetaxel.Neurology 46:104–108, 1996.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  13. Lipton RB, Apfel SC, Dutcher JP, Rosenburg R, Kaplan J, Berger A, Einzig AI, Wiernik P, Schaumburg HH: Taxol produces a predominantly sensory neuropathy.Neurology 39:368–373, 1989.

    PubMed  CAS  Google Scholar 

  14. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, van der Burg MEL, Kerr I, Vermorken JB, Buser K, Colombo N, Bacon M, Santabárbara P, Onetto N, Winograd B, Canetta R: European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: High-dose versus low-dose and long versus short infusion.J Clin Oncol 12:2654–2666, 1994.

    PubMed  CAS  Google Scholar 

  15. Smith RE, Brown AM, Mamounas EP, Anderson SJ, Lembersky BC, Atkins JH, Shibata HR, Baez L, DeFusco PA, Davila E, Tipping SJ, Bearden JD, Thirlwell MP: Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26.J Clin Oncol 17:3403–3411, 1999.

    PubMed  CAS  Google Scholar 

  16. Markman M: Managing taxane toxicities.Support Care Cancer 11:144–147, 2003.

    PubMed  Google Scholar 

  17. Wiernik PH, Schwartz EL, Einzig A, Strauman JJ, Lipton RB, Dutcher JP: Phase I trial of taxol given as a 24-hour infusion every 21 days: response observed in metastatic melanoma.J Clin Oncol 5:1232–1239, 1987.

    PubMed  CAS  Google Scholar 

  18. Connelly E, Markman M, Kennedy A, Webster K, Kulp B, Peterson G, Belinson J: Paclitaxel delivered as a 3-hr infusion with cisplatin in patients with gynecologic cancers: Unexpected incidence of neurotoxicity.Gynecolog Oncol 62:166–168, 1996.

    Article  CAS  Google Scholar 

  19. Dreicer R, Manola J, Roth BJ, Cohen MB, Hatfield AK, Wilding G: Phase II study of cisplatin and paclitaxel in advanced carcinoma of urothelium: an Eastern Cooperative Oncology Group study.J Clin Oncol 18:1058–1061, 2000.

    PubMed  CAS  Google Scholar 

  20. Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Anderson JE, Zee B, Paul J, Baron B, Pecorelli S: Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: Three-year results.J Natl Cancer Inst 92:699–708, 2000.

    Article  PubMed  CAS  Google Scholar 

  21. McKeage MJ, Haddad GG, Ding L, Galettis P, Screnci D, Zhuang L, Baguley BC: Neuroprotective interactions in rats between paclitaxel and cisplatin.Oncol Res 11:287–293, 1999.

    PubMed  CAS  Google Scholar 

  22. Mano K: Countermeasures to neurological adverse reactions of chemotherapy.Jpn J Cancer Chemother 30:779–786, 2003 (in Japanese with English abstract).

    Google Scholar 

  23. Hilkens PHE, van den Bent MJ: Chemotherapy-induced peripheral neuropathy.J Peripher Nerv Syst 2:350–361, 1997.

    PubMed  CAS  Google Scholar 

  24. Apfel SC: Managing the neurotoxicity of paclitaxel (taxol) and docetaxel (taxotere) with neurotrophic factors.Cancer Invest 18:564–574, 2000.

    Article  PubMed  CAS  Google Scholar 

  25. Hayakawa K, Sobue G, Itoh T, Mitsuma T: Nerve growth factor prevents neurotoxic effects of cisplatin, vincristine and taxol,on adult rat sympathetic ganglion expiants in vitro.Life Sci 55:519–525, 1994.

    Article  PubMed  CAS  Google Scholar 

  26. Apfel SC, Lipton RB, Arezzo JC, KesslerJA: Nerve growth factor prevents toxic neuropathy in mice.Ann Neurol 29:87–90, 1991.

    Article  PubMed  CAS  Google Scholar 

  27. Peterson ER, Crain SM: Nerve growth factor attenuates neurotoxic effects of taxol on spinal cord-ganglion expiants from fetal mice.Science 217:377–379, 1982.

    Article  PubMed  CAS  Google Scholar 

  28. Hayakawa K, Itoh T, Niwa H, Mutoh T, Sobue G: NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: In vitro study of adult rat sympathetic ganglion expiants.Brain Res 794:313–319, 1998.

    Article  PubMed  CAS  Google Scholar 

  29. Apfel SC, Kessler JA, Adornato BT, Litchy WJ, Sanders C, Rask CA and the NGF Study Group: Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy.Neurology 51:695–702, 1998.

    PubMed  CAS  Google Scholar 

  30. Hamers FP, Pette C, Neijt JP, Gispen WH: The ACTH-(4-9) analogue, ORG 2766, prevents taxol-induced neuropathy in rats.Eur J Pharmacol 233:177–178, 1993.

    Article  PubMed  CAS  Google Scholar 

  31. Lewis ME, Neff NT, Contreras PC, Stong DV, Oppenheim RW, Grebow PE, Vaught JL: Insulin-like growth factor-I: Potential for treatment of motor neuronal disorders.Exp Neurol 124:73–88, 1993.

    Article  PubMed  CAS  Google Scholar 

  32. Campana WM, Eskland N, Calcutt NA, Misasi R, Myers RR, O’Brien JS: Prosaptide prevents paclitaxel neurotoxicity.Neurotoxicology 19:237–244, 1998.

    PubMed  CAS  Google Scholar 

  33. Kilpatrick TJ, Phan S, Reardon K, Lopes EC, Cheema SS: Leukemia inhibitory factor abrogates paclitaxel-induced axonal atrophy in Wister rat.Brain Res 911:163–167, 2001.

    Article  PubMed  CAS  Google Scholar 

  34. Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, Garrett T, Savage D, Antman K, Hesdorffer CS, Balmaceda C: Reduction of paclitaxel-induced neuropathy with glutamine.Clin Cancer Res 7:1192–1197, 2001.

    PubMed  CAS  Google Scholar 

  35. Hasegawa K, Mizutani Y, Kuramoto H, Nagao S, Masuyama H, Hongo A, Kodama J, Yoshinouchi M, Hiramatsu Y, Kudo T, Okuda H: The effect of glutamine and Shakuyaku-Kanzo-to for paclitaxel-induced myalgia/arthralgia.Jpn J Cancer Chemother 29:569–574, 2002 (in Japanese with English abstract).

    Google Scholar 

  36. Durand JP, Goldwasser F: Dramatic recovery of pacli-taxel-disabling neurosensory toxicity following treatment with venlafaxine.Anti-Cancer Drugs 13:777–780, 2001.

    Article  Google Scholar 

  37. DiPaola RS, Schuchter L: Neurologic protection by amifostine.Semin Oncol 26:82–88, 1999.

    PubMed  CAS  Google Scholar 

  38. Schuchter LM: Current role of protective agents in cancer treatment.Oncology 11:505–512, 1997.

    PubMed  CAS  Google Scholar 

  39. Schuller J, Czejka M, Piertzak C, Springer B, Wirth M, Schernthaner G: Influence of the cytoprotective agent amifostine on pharmacokinetics of paclitaxel and taxotere.Proc Am Soc Clin Oncol 16:224a, 1997 (abstr).

    Google Scholar 

  40. Lorusso D, Ferrandina G, Greggi S, Gadducci A, Pignata S, Tateo S, Biamonte R, Manzione L, Vagno GD, Ferrau F, Scambia G on behalf of MITO (MulticenterItalian Trials in Ovarian Cancer) investigators: Phasegn III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients.Ann Oncol 14:1086–1093, 2003.

    Article  PubMed  CAS  Google Scholar 

  41. Leong SS, Tan EH, Fong KW, Wilder-Smith E, Ong YK, Tai BC, Chew L, Lim SH, Wee J, Lee KM, Foo KF, Ang P, Ang PT: Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage IE non-small-cell lung cancer.J Clin Oncol 21:1767–1774, 2003.

    Article  PubMed  CAS  Google Scholar 

  42. Rick O, Beyer J, Schwella N, Schubart H, Schleicher J, Siegert W: Assessment of amifostine as protection from chemotherapy-induced toxicities after conventional-dose and high-dose chemotherapy in patients with germ cell tumor.Ann Oncol 12:1151–1155, 2001.

    Article  PubMed  CAS  Google Scholar 

  43. Almadrones L, Armstrong T, Gilbert M, Schuwartz B: Chemotherapy-induced neurotoxicity: Current trends in management. Phillips Group Communications Co., Philadelphia, pp1–22, 2002.

    Google Scholar 

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  1. Department of Surgery, Niigata Prefectural Sakamachi Hospital, 589 Ooaza-Shimokajiya, Arakawamachi, 959-3193, Iwafune-gun, Niigata, Japan

    Harubiko Makino

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Makino, H. Treatment and care of neurotoxicity from taxane anticancer agents. Breast Cancer 11, 100–104 (2004). https://doi.org/10.1007/BF02968011

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  • DOI: https://doi.org/10.1007/BF02968011

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