Skip to main content
SpringerLink
Log in

Hypersensitivity Reactions to the Taxanes Paclitaxel and Docetaxel

  • Adverse Drug Experience
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Summary

Paclitaxel and docetaxel are taxane derivatives with a significant antitumour activity. For both drugs, a high incidence of hypersensitivity reactions (HSRs) has been observed during the initial clinical development. However, current pretreatment regimens, consisting of corticosteroids and antihistamines, have led to a substantial decrease in major HSRs. In this study, we describe a case series of 9 out of a total of 415 patients from eight different taxane studies who received either paclitaxel or docetaxel and experienced severe HSRs, despite the use of premedication. Five of these 9 patients had allergies or atopy. We observed an increase in blood pressure during the HSR in 5 patients, whereas a decrease was anticipated. Retreatments, with additional corticosteroids, antihistamines and in some cases a lower infusion rate, were performed successfully in 7 patients. One of these patients was given, after two courses with HSR symptoms, sodium cromoglycate as prophylaxis, after which she received four successive courses without symptoms of HSR.

In conclusion, premedication given before taxane infusions did not guarantee prevention of HSRs. We observed that these reactions did not resemble anaphylactic reactions in that there were unexpected increases in blood pressure. Retreatments were possible in most cases after appropriate measures were taken.

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

Similar content being viewed by others

References

  1. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979; 277: 665–7

    Article  PubMed  CAS  Google Scholar 

  2. Wani MC, Taylor HL, Wall ME. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971; 93: 2325–7

    Article  PubMed  CAS  Google Scholar 

  3. Rowinsky EK, Onetto N, Canetta R, et al. Taxol, the first of the taxanes, an important new class of antitumor agents. Semin Oncol 1992; 19: 646–62

    PubMed  CAS  Google Scholar 

  4. Rowinsky EK, Donehower RC. Paclitaxel (Taxol). N Engl J Med 1995; 332: 1005–14

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Rowinsky EK, McGuire WP, Guarnieri T, et al. Cardiac disturbances during the administration of taxol. J Clin Oncol 1991; 9: 1704–12

    PubMed  CAS  Google Scholar 

  7. Onetto N, Canetta R, Winograd B, et al. Overview of Taxol safety. Monogr Nad Cancer Inst 1993; 15: 131–9

    Google Scholar 

  8. Arbuck SG, Strauss H, Rowinsky EK, et al. A reassessment of cardiac toxicity associated with Taxol. Monogr Natl Cancer Inst 1993; 15: 117–30

    PubMed  Google Scholar 

  9. Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from taxol. J Clin Oncol 1990; 8: 1263–8

    PubMed  CAS  Google Scholar 

  10. Kris MG, O’Connell JP, Gralla RJ, et al. Phase I trial of taxol given as a 3h infusion every 21 days. Cancer Treat Rep 1986; 70: 605–7

    PubMed  CAS  Google Scholar 

  11. National Cancer Institute, Bethesda, MD, Division of Cancer Treatment. Clinical Brochure: Taxol (NSC-125973), 1991

  12. Greenberger PA, Patterson R, Simon R, et al. Pretreatment of high-risk patients requiring radiographic contrast media studies. J Allergy Clin Immunol 1981; 67: 185–7

    Article  PubMed  CAS  Google Scholar 

  13. Weiss RB. Hypersensitivity reactions. Semin Oncol 1992; 19: 458–77

    PubMed  CAS  Google Scholar 

  14. Rowinsky EK, Eisenhauer EA, Chaudhry V, et al. Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 1993; 20 Suppl. 3: 1–15

    PubMed  CAS  Google Scholar 

  15. Eisenhauer EA, Ten Bokkel Huinink WW, Swenerton KD, et al. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose vs low-dose and long vs short infusion. J Clin Oncol 1994; 12: 2654–66

    PubMed  CAS  Google Scholar 

  16. Ringel I, Horwitz SB. Studies with RP 56976 (Taxotere): A semi-synthetic analogue of taxol. J Natl Cancer Inst 1991; 83: 288–91

    Article  PubMed  CAS  Google Scholar 

  17. Cortes JE, Pazdur R. Docetaxel. J Clin Oncol 1995; 13: 2643–55

    PubMed  CAS  Google Scholar 

  18. Verweij J, Clavel M, Chevalier B. Paclitaxel and docetaxel, not simply two of a kind. Ann Oncol 1994; 5: 495–505

    PubMed  CAS  Google Scholar 

  19. Wanders J, Schrijvers D, Bruntsch U, et al. The EORTC-ECTG experience with acute hypersensitivity reactions (HSR) in Taxotere studies [abstract 94]. Proc Am Soc Clin Oncol 1993; 12: 73

    Google Scholar 

  20. Fumoleau P, Chevalier B, Kerbrat P, et al. Current status of Taxotere as a new treatment in breast cancer. Breast Cancer Res Treat 1994; 33: 39–46

    Article  Google Scholar 

  21. Trudeau ME, Eisenhauer EA, Higgins BP, et al. Docetaxel in patients with metastatic breast cancer: a phase II study of the National Cancer Institute of Canada — Clinical Trials Group. J Clin Oncol 1996; 14: 422–8

    PubMed  CAS  Google Scholar 

  22. Peereboom D, Donehower RC, Eisenhauer EA, et al. Successful retreatment with Taxol after major hypersensitivity reactions. J Clin Oncol 1993; 11: 885–90

    PubMed  CAS  Google Scholar 

  23. Schrijvers D, Wanders J, Dirix L, et al. Coping with the toxicities of docetaxel (Taxotere). Ann Oncol 1993; 4: 610–1

    PubMed  CAS  Google Scholar 

  24. Del Priore G, Smith P, Warshal DP, et al. Paclitaxel-associated hypersensitivity reaction despite high-dose steroids and prolonged infusions. Gynecol Oncol 1995; 56: 316–8

    Article  PubMed  Google Scholar 

  25. Giaccone G, Huizing MT, Postmus PE, et al. Dose-finding and sequencing study of paclitaxel and carboplatin in non-small cell lung cancer, an interim report. Semin Oncol 1995: 22 (4 Suppl. 9): 78–82

    PubMed  CAS  Google Scholar 

  26. Huizing MT, Rosing H, Vermorken JB, et al. Increased paclitaxel and metabolism levels in patients with altered hepatic function [abstract 379]. Proc Am Soc Clin Oncol 1996; 15: 182

    Google Scholar 

  27. Giaccone G, Huizing MT, Ten Bokkel Huinink WW, et al. Preliminary results of two dose-finding studies of paclitaxel and carboplatin in non-small cell lung and ovarian cancers: a European Cancer Centre effort. Semin Oncol 1994; 21 (5 Suppl. 8): 34–8

    PubMed  CAS  Google Scholar 

  28. Vermorken JB, Ten Bokkel Huinink WW, Mandjes IA, et al. High-dose paclitaxel with granulocyte colony-stimulating factor in patients with advanced breast cancer refractory to anthracycline therapy: a European Cancer Centre effort. Semin Oncol 1995; 22 (4 Suppl. 8): 16–22

    PubMed  CAS  Google Scholar 

  29. Ten Bokkel Huinink WW, Dubbelman R, Hiemstra A, et al. Phase I study of docetaxel alternating with epirubicin and cyclofosfamide in an escalated and accelerated schedule by the concomitant use of lenograstim [abstract 299]. Proc Am Soc Clin Oncol 1996; 15: 141

    Google Scholar 

  30. Westermann AM, Ten Bokkel Huinink WW, Rodenhuis S. Successful docetaxel rechallenge with cromoglycate after major sensitivity reactions. Ann Oncol 1996; 7: 104

    Article  PubMed  CAS  Google Scholar 

  31. Lasser EC, Walters A, Reuter SR, et al. Histamine release by contrast media. Radiology 1971; 100: 683–6

    PubMed  CAS  Google Scholar 

  32. Terr AI. Anaphylaxis and urticaria. In: Stites DP, Terr AI, Parslow TG, editors. Basic and clinical immunology. 8th ed. Norwalk, CT: Appleton and Lange, 1994: 347–56

    Google Scholar 

  33. Dorr RT. Pharmacology and toxicology of Cremophor EL. Ann Pharmacother 1994; 28: S11–S34

    PubMed  CAS  Google Scholar 

  34. Theis JGW, Liau-Chu M, Chan HSL, et al. Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance: the causative role of improper dissolution of Cremophor EL. J Clin Oncol 1995; 13: 2508–16

    PubMed  CAS  Google Scholar 

  35. Lorenz W, Reimann HJ, Schmal A, et al. Histamine release in dogs by Cremophor EL and its derivatives: oxethylated oleic acid is the most effective constituent. Agents Actions 1977; 7: 63–7

    Article  PubMed  CAS  Google Scholar 

  36. Whitworth JA. Adrenocorticotrophin and steroid-induced hypertension in humans. Review. Kidney Intern Suppl. 1992; 37: S34–S37

    CAS  Google Scholar 

  37. Weir MR, Klassen DK, Shen SY, et al. Acute effects of intravenous cyclosporine on blood pressure, renal hemodynamics and urine prostaglandin production of healthy humans. Transplantation 1990; 49: 41–7

    Article  PubMed  CAS  Google Scholar 

  38. Piccart MJ, Gore M, Ten Bokkel Huinink WW, et al. Taxotere, an active new drug for the treatment of advanced ovarian cancer. J Natl Cancer Inst 1995; 87: 676–81

    Article  PubMed  CAS  Google Scholar 

  39. Mertens WC, Eisenhauer EA, Solivet J, et al. Docetaxel in advanced renal carcinoma. A Phase II trial of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 1994; 5: 185–7

    PubMed  CAS  Google Scholar 

  40. Donehower RC, Rowinsky EK, Grochow LB, et al. Phase I trial of taxol in patients with advanced cancer. Cancer Treat Rep 1987; 71: 1171–7

    PubMed  CAS  Google Scholar 

  41. Ettinger DS, Finkelstein DM, Sarma RP, et al. Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer; an Eastern Cooperative Oncology Group study. J Clin Oncol 1995; 13: 1430–5

    PubMed  CAS  Google Scholar 

  42. Solimando Jr. DA, Phillips ET, Weiss RB, et al. Hypertensive reactions associated with paclitaxel. Cancer Invest 1996; 14: 340–2

    Article  PubMed  CAS  Google Scholar 

  43. Wilson WH, Berg SL, Bryant G, et al. Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96-hour infusion. J Clin Oncol 1994; 12: 1621–9

    PubMed  CAS  Google Scholar 

  44. Seidman AD, Hochhauser D, Gollub M, et al. Ninety-six hour paclitaxel infusion after progression during short taxane exposure: a phase II pharmacokinetic and pharmacodynamic study in metastatic breast cancer. J Clin Oncol 1996; 14: 1877–84

    PubMed  CAS  Google Scholar 

  45. Sharma A, Straubinger RM. Novel Taxol formulations: preparation of Taxol containing liposomes. Pharmaceutical Res 1994; 11: 889–96

    Article  CAS  Google Scholar 

  46. Meerum Terwogt J, Nuijen B, Ten Bokkel Huinink WW et al. Alternative formulations of paclitaxel. Cancer Treat Rev 1997; 23: 87–96

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Vinodh R. Nannan Panday, Manon T. Huizing, Wim W. Ten Bokkel Huinink & Jos H. Beijnen

  2. Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands

    Vinodh R. Nannan Panday, Manon T. Huizing & Jos H. Beijnen

  3. Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    Manon T. Huizing & Jan B. Vermorken

  4. Department of Pharmaceutical Analysis and Toxicology, Faculty of Pharmacy, State University of Utrecht, Utrecht, The Netherlands

    Jos H. Beijnen

Authors
  1. Vinodh R. Nannan Panday
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manon T. Huizing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wim W. Ten Bokkel Huinink
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jan B. Vermorken
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jos H. Beijnen
    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

Panday, V.R.N., Huizing, M.T., Ten Bokkel Huinink, W.W. et al. Hypersensitivity Reactions to the Taxanes Paclitaxel and Docetaxel. Clin. Drug Invest. 14, 418–427 (1997). https://doi.org/10.2165/00044011-199714050-00011

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-199714050-00011

Keywords

Search

Navigation