Hypersensitivity reactions to chemotherapeutic drugs


There is an ever-increasing number of therapeutics used to treat cancer. A recent publication listed 86 currently available antineoplastic medications. Despite this large number, hypersensitivity reactions are not common except with platinum compound (cisplatin, carboplatin), epipodophyllotoxins (teniposide, etoposide), asparaginase, taxanes (paclitaxel), and procarbazine. Doxorubicin and 6-mercaptopurine are occasionally associated with hypersensitivity reaction. Comparable reactions with other chemotherapeutic agents are. uncommon; many are only anecdotal reports. Reactions associated with individual drugs are discussed in detail.

The mechanisms responsible for most of these reactions are not known, as they have generally not been evaluated. The term “hypersensitivity” is widely used in the chemotherapy literature without a common definition. Hypersensitivity is defined here as an unexpected reaction with signs and symptoms not consistent with known toxicity of the drug. Most reactions are coincident with or within hours of drug administration. Almost all are associated with parenteral administration. Symptoms include flushing, alterations in heart rate and blood pressure, dyspnea and bronchospasm, back pain, fever, pruritus, nausea and all types of rashes. Some cases may be due to non-immune mediated release of histamine or cytokines, as many patients can subsequently tolerate re-exposure after pretreatment with steroids and antihistamine, and slow readministration of the drug. This is more compatible with a graded challenge, than desensitization and is generally successful for taxanes less so for platinum compounds.

In most cases hypersensitivity reactions are associated with the specific chemotherapeutic drug. Reaction rates may vary with different forms of the drugs, e.g. pegylated. Occasionally excipients such as Cremaphor EL may induce hypersensitivity reactions.

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


  1. 1.

    Drugs of Choice for Chemotherapy, in The Medical Letter, vol. 42, Abramowicz, M., ed., September 18, 2000, pp. 83–92.

  2. 2.

    Zanotti, K. M. and Markman, M. (2001), Drug Saf. 24, 767–779.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Robinson, J. B., Singh, D., Bodurka-Bevers, D. C., Wharton, J. T., Gershenson, D. M., and Wolf, J. K. (2001), Gynecol. Oncol. 82, 550–558.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Stone, H. D., DiPiro, C., Davis, P. C., Meyer, C. F., and Wray, B. B. (1998), J. Allergy Clin. Immunol. 101, 429–431.

    PubMed  Article  Google Scholar 

  5. 5.

    Weiss, R. B. (1992), Sem. Oncol. 19, 458–477.

    CAS  Google Scholar 

  6. 6.

    Larson, R. A., Fretzin, M. H., Dodge, R. K., and Schiffer, C. A. (1998), Leukemia 12, 660–665.

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Mueller, H.J., Beir, R., Loning, L., et al. (2001), Br. J. Haematol. 114, 794–799.

    Article  Google Scholar 

  8. 8.

    Physicians Desk Reference 2001, Publishers Medical Economics, Montvale, NJ, p. 1928.

  9. 9.

    Woo, M. H., Storm, L. J., Sandlund, J. T., Ribeiro, R. C., et al. (2000), J. Clin. Oncol. 18, 1525–1532.

    PubMed  CAS  Google Scholar 

  10. 10.

    Zanotti, K. M., Rybicki, L. A., Kennedy, A. W., Belinson, J. L., et al. (2001), J. Clin. Oncol. 19, 3126–3129.

    PubMed  CAS  Google Scholar 

  11. 11.

    Polyzos, A., Tsavaris, N., Kosmas, C., Arnaouti, T., et al. (2001), Oncology 61, 129–133.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Shukunami, K., Kurokawa, T., Kawakami, Y., Kubo, M., and Kotsuji, F. (1999), Gynecol. Oncol. 72, 431–432.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Markman, M., Kennedy, A., Webster, K., Elson, P., et al. (1999), J. Clin. Oncol. 17, 1141.

    PubMed  CAS  Google Scholar 

  14. 14.

    Goldberg, A., Confino-Cohen, R., Fishman, A., Beyth, Y., and Altaras, M. (1996), J. Allergy Clin. Immunol. 98, 841–843.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Kellie, S. J., Crist, W. M., Pui, C. H., Crone, M. E., Fairclough, D. L., Rodman, J. H., et al. (1991), Cancer 67, 1070–1075.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Hudson, M. N., Weinstein, H. J., Donaldson, S. S., Greewald, C., Kun, L., et al. (1993), J. Clin. Oncol. 11, 1080–1084.

    PubMed  CAS  Google Scholar 

  17. 17.

    Szebeni, J., Alving, C. R., Savay, S., Barenholz, Y., et al. (2001), Int. Immunopharmacol. 1, 721–735.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Nolte, H., Carstensen, H., and Hertz, H. (1988), Am. J. Pediatr. Hematol. Oncol. 10, 308–312.

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    Hoetelmans, R. M., Schornagel, J. H., ten Bokkel Huinink, W. W., and Beijnen, J. H. (1996), Ann. Pharmacother. 30, 367–371.

    PubMed  CAS  Google Scholar 

  20. 20.

    Grosen, E. (2000), Lancet 354, 288–289.

    Article  Google Scholar 

  21. 21.

    Myers, J. (2000), Clin. J. Oncol. Nurs. 4, 161–163.

    PubMed  CAS  Google Scholar 

  22. 22.

    Essayan, D. M., Kagey-Sobotka, A., Colarusco, P. J., Lichtenstein, L. M., Ozols, R. F., and King, E. D. (1996), J. Allergy Clin. Immunol. 97, 42–46.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Kintzel, P. E. (2001), Ann. Pharmacother. 35, 1114–1117.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Moon, C., Verschraegen, C. F., Bevers, M., Freedman, R., Kudelka, A. P., and Kavanagh, J. T. (2000), Anticancer Drugs 11, 565–568.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Koppler, H., Heymans, J., and Weider, R. (2001), Onkologie 24, 283–285.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Peereboom, D. M., Donehower, R. C., Eisenhauer, E. A., McGuire, W. P., et al. (1993), J. Clin. Oncol. 5, 885–890.

    Google Scholar 

  27. 27.

    Fishman, A., Gold, T., Goldberg, A., Confino-Cohen, R., et al. (1999), Int. J. Gynecol. Cancer 9, 156–159.

    PubMed  Article  Google Scholar 

  28. 28.

    Bernstein, B. J. (2000), Ann. Pharmacother. 11, 1332–1335.

    Article  Google Scholar 

  29. 29.

    Fossella, F. V., Lee, J. S., Murphy, W. K., et al. (1994), J. Clin. Oncol. 12, 1238–1244.

    PubMed  CAS  Google Scholar 

  30. 30.

    Coyle, T., Bushunow, P., Winfield, J., Wright, J., and Graziano, S. (1999), Cancer 15, 2532–2540.

    Google Scholar 

  31. 31.

    Giguere, J. K., Douglas, D. M., Lupton, G. P., Baker, J. R., and Weiss, R. B. (1988), Med. Pediatr. Oncol. 16, 378–380.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Lehmann, D. F., Hurteau, T. E., Newman, N., Coyle, T. E. (1997), Clin. Pharmacol. Ther. 62, 225–229.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Alberts, D. S. and Garcia, D. J. (1997), Drugs 54, S30-S35.

    Article  Google Scholar 

  34. 34.

    Gabizon, A. A., (2001), Cancer Investig. 19, 424–436.

    Article  CAS  Google Scholar 

  35. 35.

    Goram, A. L. and Richmond, P. L. (2001), Pharmacotherapy 6, 751–763.

    Article  Google Scholar 

  36. 36.

    Korelitz, B. I., Zlantic, J., Goel, E., and Fuller, S. (1999), J. Clin. Gastroenterol. 28, 341–344.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Torricelli, R., Kurer, S. B., Krotoner, T., and Wurtyrich, B. (1995), Schweiz Med. Wochenschr. 125, 1870–1873.

    PubMed  CAS  Google Scholar 

  38. 37a.

    Cornwell, G. G., Pajak, T. F., and McIntyre, O. R., (1979), Cancer Treat. Res. 63, 399–403.

    Google Scholar 

  39. 38.

    Popescu, N. A., Sheehan, M. G., Kouides, P. A., et al. (1996), J. Allergy Clin. Immunol. 97, 26–33.

    PubMed  Article  CAS  Google Scholar 

  40. 39.

    Rheinhold-Keller, E., Mohr, J., Christophers, E., Nordmann, K., and Gross, W. L. (1992), Clin. Investig. 70, 698–704.

    Article  Google Scholar 

  41. 40.

    Zonzits, E., Aberer, W., and Tappeiner, G. (1992), Arch. Dermatol. 128, 80–82.

    PubMed  Article  CAS  Google Scholar 

  42. 41.

    Ozkan, A., Apak, H., Celkan, T., Yuksel, L., Yildez, I. (2001), Pediatr. Dermatol. 18, 38–40.

    PubMed  Article  CAS  Google Scholar 

  43. 42.

    Blanca, M., Torres, M. J., Giron, M., Corzo, J. L., and Martinez-Valverde, A. (1997), Allergy 52, 1009–1011.

    PubMed  Article  CAS  Google Scholar 

  44. 43.

    Chiara, S., Nobile, M. T., Barzacchi, C., et al. (1997), Eur. J. Cancer 33, 967–969.

    PubMed  Article  CAS  Google Scholar 

  45. 44.

    Sandhu, H. S., Barnes, P. J., and Hernandez, P. (2000), Can. Resp. J. 7, 491–495.

    CAS  Google Scholar 

  46. 45.

    Alkins, S. A., Byrd, J. C., Morgan, S. K., Ward, F. T., and Weiss, R. B. (1996), Cancer 15, 2123–2126.

    Article  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shepherd, G.M. Hypersensitivity reactions to chemotherapeutic drugs. Clinic Rev Allerg Immunol 24, 253–262 (2003). https://doi.org/10.1385/CRIAI:24:3:253

Download citation

Index Entries

  • Hypersensitivity
  • allergy
  • chemotherapy
  • desensitization
  • drug asparaginase
  • platinum compounds
  • epipodophyllotoxins
  • taxanes