Skip to main content
SpringerLink
Log in

Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Background. Paclitaxel-induced peripheral neuropathy (PN) may be severeand dose-limiting at initial doses ≥ 275 mg/M2, but itsneurotoxicity at doses ≤ 250 mg/M2 has been incompletelycharacterized. The purposes of this study were to characterize and quantifypaclitaxel-induced PN and to determine the utility of quantitative sensorytesting (QST). Methods. We prospectively examined clinically and by QST 37women with metastatic breast cancer, treated with paclitaxel (200–250mg/m2) (average number of cycles = 7.3 over an average of 20.1weeks). QST included thermal threshold (TT) and vibration threshold (VT).Results. Paresthesias appeared in 31 (84%) patients after an averageof 1.7 cycles and an average cumulative dose of 371.5 mg/M2. Symptomsoccurred after the first or second dose in 26 (84%) patients and thenstabilized in 10 (32%), improved in 13 (42%) despite continuedtreatment, resolved completely in 6 (19%), and were progressive in 2(7%). Paclitaxel was discontinued in only 1 (3%) patientbecause of neurotoxicity and no patient required dose reduction because ofPN. Thirty-six (97%) developed signs of PN. The most sensitive QSTwas great toe VT but QST did not predict or identify subclinical PN in anypatient. Neurologic syndromes other than PN developed in 12 (32%)patients, and 7 were due to metastatic cancer. Conclusions. 1)Paclitaxel-induced PN is mostly sensory, and begins after the first orsecond dose. At these doses the neuropathy is mild, and rarelydose-limiting. 2) QST quantified the neuropathy but was less sensitive thanthe clinical examination. 3) Knowledge of the features of paclitaxel's PNallows it to be differentiated from other neurologic syndromes which maysignal tumor progression.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. McGuire WP, Rowinsky EK, Rosenheim NB, Grumbine FC, Ettinger DS, Armstrong DK, Donehower RC: Taxol: A unique antineoplastic agent with significant activity in advanced epithelial neoplasms. Ann Int Med 111: 273–279, 1989

    Google Scholar 

  2. Thigpen T, Blessing J, Ball H, Hummel S, Barret R: Phase 2 trial of Taxol as a second-line therapy for ovarian carcinoma: A Gynecologic Oncology Group Study (Abstract). Proc Amer Soc Clin Oncol 9: 156, 1990

    Google Scholar 

  3. Schiff PB, Horowitz SB: Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci 77: 1561–1565, 1980

    Google Scholar 

  4. Rowinsky EK, Cazenave LA, Donehower RC: Taxol: A novel investigational antimicrotubule agent. J Natl Cancer Inst 82: 1247–1259, 1990

    Google Scholar 

  5. Bogdan C, Ding A: Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-1 in macrophages. J Leukoc Biol 52: 119–121, 1992

    Google Scholar 

  6. Wiernik PH, Schwartz EL, Enzig A, et al.: Phase 1 trial of Taxol given as a 24-hr infusion every 21 days: Responses observed in metastatic melanoma. J Clin Oncol 5: 1232–1239, 1987b.

    Google Scholar 

  7. Sarosy G, Kohn E, Stone DA, et al.: Phase 1 study of Taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer. J Clin Oncol 10: 1165–1170, 1992

    Google Scholar 

  8. Schiller JH, Storer B, Tutsch K, et al.: Phase 1 trial of 3-hour infusion of paclitaxel with or without granulocyte colony stimulating factor in patients with advanced cancer. J Clin Oncol 12: 241–248, 1994

    Google Scholar 

  9. Rowinsky EK, Chaudry V, Forastiere AA, et al.: Phase 1and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: Neuromuscular toxicity is dose-limiting. J Clin Oncol 11: 2010–2020, 1993

    Google Scholar 

  10. Chaudry V, Rowinsky EK, Sartorius SE, et al.: Peripheral neuropathy from Taxol and cisplatin combination chemotherapy: Clinical and electrophysiologic studies. Ann Neurol 35: 304–311, 1994

    Google Scholar 

  11. Arezzo JC, Schaumburg HH, Petersen CA: Rapid screening for peripheral neuropathy: A field study with the Optacon. Neurology 33: 626–629, 1983

    Google Scholar 

  12. Bove F, Litwak MS, Arezzo JC, Baker EL: Quantitative sensory testing in occupational medicine. Semin Occupat Med 1: 185–189, 1986

    Google Scholar 

  13. Rendell MS, Katims JJ, Richter R, Rowland F: A comparison of nerve conduction velocities and current perception thresholds as correlates of clinical severity of diabetic sensory neuropathy. J Neurol Neurosurg Psychiat 52: 502–511, 1989

    Google Scholar 

  14. Gulevich SJ, Kalmijn JA, Thal LJ, et al.: Sensory testing in human immunodeficiency virus type 1 infected men. Arch Neurol 49: 1281–1284, 1992

    Google Scholar 

  15. Redmond JMT, McKenna MJ, Feingold M, Ahmad BK: Sensory testing versus nerve conduction velocity in diabetic polyneuropathy. Muscle & Nerve 15: 1334–1339, 1992

    Google Scholar 

  16. Consensus report from the Peripheral Neuropathy Association: Quantitative sensory testing: A consensus report from the Peripheral Neuropathy Association. Neurology 43: 1050–1052, 1993

    Google Scholar 

  17. Verdugo R, Ochoa JL: Quantitative somatosensory thermotest. Brain 115: 893–913, 1992

    Google Scholar 

  18. Peterson K, Forsyth P, Posner JB: Paraneoplastic sensorimotor polyneuropathy in patients with breast cancer. J Neuro-Oncol 21: 159–170, 1994

    Google Scholar 

  19. Donehower RC, Rowinsky EK, Grochow LB, et al.: Phase 1 trial of Taxol in patients with advanced cancer. Cancer Treat Rep 71: 1171–1177, 1987

    Google Scholar 

  20. Brown T, Havlin K, Weiss G, et al.: A phase 1 trial of Taxol given by a six hour intravenous infusion. J Clin Oncol 9: 1261–1267, 1991

    Google Scholar 

  21. ten Bokkel Huinink WW, Eisenhauer E, Swenerton K: Preliminary evaluation of a multicenter, randomized comparative study of Taxol (paclitaxel) dose and infusion length in platinum treated ovarian cancer. Cancer Treat Rev 19 (Suppl C): 79–86, 1993

    Google Scholar 

  22. Wiernik PH, Schwartz EL, Strauman JJ, et al.: Phase 1 clinical and pharmacokinetic study of Taxol. Cancer Res 47: 2486–2493, 1987a

    Google Scholar 

  23. Postma TJ, Liefting AJM, Heimans JJ, et al.: Neurotoxicity in patients with breast cancer (BC) and ovarian cancer (OV) treated with Taxol (Abstract). Proc Amer Soc Clin Oncol 12: 64, 1993

    Google Scholar 

  24. Legha SS, Tenney DM, Krakoff IR: Phase I study of Taxol using a 5-day intermittent schedule. J Clin Oncol 4: 762–766, 1986

    Google Scholar 

  25. Seidman A, Reichman B, Crown J, et al.: Taxol as second and subsequent therapy for metastatic breast cancer: Activity independent of prior anthracycline response. J Clin Oncol 13: 1152–1159, 1995

    Google Scholar 

  26. Reichman BS, Seidman AD, Crown JPA, et al.: Taxol and recombinant human granulocyte colony-stimulating factors as initial chemotherapy for metastatic breast cancer. J Clin Oncol 11: 1943–1951, 1991

    Google Scholar 

  27. Einzig AI, Hochster H, Wiernik PH, et al.: A phase 2 study of Taxol in metastatic melanoma. Invest New Drugs 9: 59–64, 1991a

    Google Scholar 

  28. Einzig AI, Gorowski E, Sasloff J, et al.: Phase 2 trial of Taxol in patients with metastatic renal cell carcinoma. Cancer 9: 133–136, 1991b

    Google Scholar 

  29. Einzig AI, Wiernik PH, Sasloff J: Phase II study and long term follow-up of patients treated with Taxol for advanced ovarian adenocarcinoma. J Clin Oncol 10: 1748–1753, 1992

    Google Scholar 

  30. Chang A, Kim K, Glick J, et al.: Phase 2 study of Taxol in patients with stage 4 non-small cell lung cancer: ECOG Results (Abstract). Proc Amer Soc Clin Oncol 11: 293, 1992

    Google Scholar 

  31. Kohn EC, Sarosy G, Bicher A, et al.: Dose-intense Taxol: High response rate in patients with platinum-resistant recurrent ovarian cancer. J Natl Cancer Inst 86: 18–24, 1994

    Google Scholar 

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

    Google Scholar 

  33. Apfel SC, Lipton RB, Arrezo JC, et al.: Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol 29: 87–90, 1991

    Google Scholar 

  34. Rowinsky EK, Gilbert MR, McGuire WP, et al.: Sequences of Taxol and cisplatin: A phase I and pharmacologic study. J Clin Oncol 9: 1692–1703, 1991

    Google Scholar 

  35. van Gerven JMA, Moll JWB, van den Bent MJ, et al.: Paclitaxel (Taxol) induces cumulative mild neurotoxicity. Eur J Cancer 30A: No. 8, 1074–1077, 1994

    Google Scholar 

  36. Kaplan JG, Einzig AI, Schaumburg HH: Taxol causes permanent large fiber peripheral nerve dysfunction: A lesson for preventative strategies. J Neuro-Oncol 16: 105–107, 1993

    Google Scholar 

  37. Holmes FA, Walter RS, Theriault RL, et al.: Phase 2 trial of Taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst 83: 1797–1805, 1991

    Google Scholar 

  38. Trimble EL, Adams JD, Vena D, Hawkins MJ, et al.: Taxol for platinum-refractory ovarian cancer: Results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103. J Clin Oncol 11: 2405–2410, 1993

    Google Scholar 

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

    Google Scholar 

  40. Sahenk Z, Barohn R, New P, et al.: Taxol neuropathy. Electrodiagnostic and sural nerve biopsy findings. Arch Neurol 51: 726–729, 1994

    Google Scholar 

  41. Donehower RC, Rowinsky EK: An overview of experience with Taxol (paclitaxel) in the USA. Cancer Treat Rev 19 (Suppl C): 63–78, 1993

    Google Scholar 

  42. Seidman AD, Barrett S, Canezo S: Photopsia during 3-hour Taxol administration at doses ??250 mg/M2. J Clin Oncol 12: 1741–1742, 1994

    Google Scholar 

  43. Capri E, Munzone E, Tarenzi, Fulfaro, Gianni L: Optic nerve disturbances: A new form of paclitaxel neurotoxicity. J Natl Cancer Inst 86: 1099–1101, 1994

    Google Scholar 

  44. Siegal T, Haim N: Cisplatin-induced peripheral neuropathy. Frequent off-therapy deterioration, demyelinating syndromes, and muscle cramps. Cancer 66: 1117–1123, 1990

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Memorial Sloan-Kettering Cancer Center, USA

    Peter a. Forsyth, Casilda Balmaceda, Kendra Peterson & Lisa M. Deangelis

  2. Department of Medicine, Memorial Sloan-Kettering Cancer Center, USA

    Andrew D. Seidman

  3. Department of Neurology and Neurosciences, Cornell University Medical College, New York

    Peter a. Forsyth, Casilda Balmaceda, Kendra Peterson & Lisa M. Deangelis

  4. Division of Epidemiology and Preventive Oncology, Tom Baker Cancer Center, Calgary, Canada

    Penny Brasher

  5. Department of Medicine, Tom Baker Cancer Center, USA

    Peter a. Forsyth

  6. Department of Neurology, Neurologic Institute, Columbia Presbyterian Medical Center, New York

    Casilda Balmaceda

  7. Department of Neurology, Stanford University Medical Center, Stanford, California, USA

    Kendra Peterson

  8. Department of Clinical Neuro-sciences, Foothills Hospital and the University of Calgary, Calgary, Alberta, Canada

    Peter a. Forsyth

Authors
  1. Peter a. Forsyth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Casilda Balmaceda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kendra Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew D. Seidman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Penny Brasher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lisa M. Deangelis
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Forsyth, P.a., Balmaceda, C., Peterson, K. et al. Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing. J Neurooncol 35, 47–53 (1997). https://doi.org/10.1023/A:1005805907311

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005805907311

Search

Navigation