Clinical Reviews in Allergy & Immunology

, Volume 24, Issue 3, pp 253–262 | Cite as

Hypersensitivity reactions to chemotherapeutic drugs

  • Gillian M. Shepherd


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.

Index Entries

Hypersensitivity allergy chemotherapy desensitization drug asparaginase platinum compounds epipodophyllotoxins taxanes 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Drugs of Choice for Chemotherapy, in The Medical Letter, vol. 42, Abramowicz, M., ed., September 18, 2000, pp. 83–92.Google Scholar
  2. 2.
    Zanotti, K. M. and Markman, M. (2001), Drug Saf. 24, 767–779.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Weiss, R. B. (1992), Sem. Oncol. 19, 458–477.Google Scholar
  6. 6.
    Larson, R. A., Fretzin, M. H., Dodge, R. K., and Schiffer, C. A. (1998), Leukemia 12, 660–665.PubMedCrossRefGoogle Scholar
  7. 7.
    Mueller, H.J., Beir, R., Loning, L., et al. (2001), Br. J. Haematol. 114, 794–799.CrossRefGoogle Scholar
  8. 8.
    Physicians Desk Reference 2001, Publishers Medical Economics, Montvale, NJ, p. 1928.Google Scholar
  9. 9.
    Woo, M. H., Storm, L. J., Sandlund, J. T., Ribeiro, R. C., et al. (2000), J. Clin. Oncol. 18, 1525–1532.PubMedGoogle Scholar
  10. 10.
    Zanotti, K. M., Rybicki, L. A., Kennedy, A. W., Belinson, J. L., et al. (2001), J. Clin. Oncol. 19, 3126–3129.PubMedGoogle Scholar
  11. 11.
    Polyzos, A., Tsavaris, N., Kosmas, C., Arnaouti, T., et al. (2001), Oncology 61, 129–133.PubMedCrossRefGoogle Scholar
  12. 12.
    Shukunami, K., Kurokawa, T., Kawakami, Y., Kubo, M., and Kotsuji, F. (1999), Gynecol. Oncol. 72, 431–432.PubMedCrossRefGoogle Scholar
  13. 13.
    Markman, M., Kennedy, A., Webster, K., Elson, P., et al. (1999), J. Clin. Oncol. 17, 1141.PubMedGoogle Scholar
  14. 14.
    Goldberg, A., Confino-Cohen, R., Fishman, A., Beyth, Y., and Altaras, M. (1996), J. Allergy Clin. Immunol. 98, 841–843.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle Scholar
  17. 17.
    Szebeni, J., Alving, C. R., Savay, S., Barenholz, Y., et al. (2001), Int. Immunopharmacol. 1, 721–735.PubMedCrossRefGoogle Scholar
  18. 18.
    Nolte, H., Carstensen, H., and Hertz, H. (1988), Am. J. Pediatr. Hematol. Oncol. 10, 308–312.PubMedCrossRefGoogle Scholar
  19. 19.
    Hoetelmans, R. M., Schornagel, J. H., ten Bokkel Huinink, W. W., and Beijnen, J. H. (1996), Ann. Pharmacother. 30, 367–371.PubMedGoogle Scholar
  20. 20.
    Grosen, E. (2000), Lancet 354, 288–289.CrossRefGoogle Scholar
  21. 21.
    Myers, J. (2000), Clin. J. Oncol. Nurs. 4, 161–163.PubMedGoogle 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.PubMedCrossRefGoogle Scholar
  23. 23.
    Kintzel, P. E. (2001), Ann. Pharmacother. 35, 1114–1117.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  25. 25.
    Koppler, H., Heymans, J., and Weider, R. (2001), Onkologie 24, 283–285.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  28. 28.
    Bernstein, B. J. (2000), Ann. Pharmacother. 11, 1332–1335.CrossRefGoogle Scholar
  29. 29.
    Fossella, F. V., Lee, J. S., Murphy, W. K., et al. (1994), J. Clin. Oncol. 12, 1238–1244.PubMedGoogle 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Lehmann, D. F., Hurteau, T. E., Newman, N., Coyle, T. E. (1997), Clin. Pharmacol. Ther. 62, 225–229.PubMedCrossRefGoogle Scholar
  33. 33.
    Alberts, D. S. and Garcia, D. J. (1997), Drugs 54, S30-S35.CrossRefGoogle Scholar
  34. 34.
    Gabizon, A. A., (2001), Cancer Investig. 19, 424–436.CrossRefGoogle Scholar
  35. 35.
    Goram, A. L. and Richmond, P. L. (2001), Pharmacotherapy 6, 751–763.CrossRefGoogle Scholar
  36. 36.
    Korelitz, B. I., Zlantic, J., Goel, E., and Fuller, S. (1999), J. Clin. Gastroenterol. 28, 341–344.PubMedCrossRefGoogle Scholar
  37. 37.
    Torricelli, R., Kurer, S. B., Krotoner, T., and Wurtyrich, B. (1995), Schweiz Med. Wochenschr. 125, 1870–1873.PubMedGoogle 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.PubMedCrossRefGoogle Scholar
  40. 39.
    Rheinhold-Keller, E., Mohr, J., Christophers, E., Nordmann, K., and Gross, W. L. (1992), Clin. Investig. 70, 698–704.CrossRefGoogle Scholar
  41. 40.
    Zonzits, E., Aberer, W., and Tappeiner, G. (1992), Arch. Dermatol. 128, 80–82.PubMedCrossRefGoogle Scholar
  42. 41.
    Ozkan, A., Apak, H., Celkan, T., Yuksel, L., Yildez, I. (2001), Pediatr. Dermatol. 18, 38–40.PubMedCrossRefGoogle Scholar
  43. 42.
    Blanca, M., Torres, M. J., Giron, M., Corzo, J. L., and Martinez-Valverde, A. (1997), Allergy 52, 1009–1011.PubMedCrossRefGoogle Scholar
  44. 43.
    Chiara, S., Nobile, M. T., Barzacchi, C., et al. (1997), Eur. J. Cancer 33, 967–969.PubMedCrossRefGoogle Scholar
  45. 44.
    Sandhu, H. S., Barnes, P. J., and Hernandez, P. (2000), Can. Resp. J. 7, 491–495.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.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Gillian M. Shepherd
    • 1
  1. 1.Weill Medical College of Cornell UniversityNew York

Personalised recommendations