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Hypersensitivity Reaction (HSR) to Docetaxel After a Previous HSR to Paclitaxel

Toowoomba Health Services, Toowoomba, Australia

To the Editor:Hypersensitivity reactions (HSRs) to paclitaxel are well described in the oncology literature.^1-4 The etiology of these reactions has been the source of much speculation, with Cremophor EL, the diluent for the insoluble paclitaxel, commonly blamed.^1,5 Premedication with corticosteroids and H₁ and H₂ receptor antagonists successfully reduces the incidence and severity of the HSR.⁵ Re-treatment strategies have been developed to allow continuation of the paclitaxel infusion after a HSR, and patients who experience a severe reaction or a second HSR after reinitiation of therapy have received further cycles after undergoing a formal desensitization protocol.^2,5 Successful substitution of paclitaxel with docetaxel, another taxane with similar efficacy, has also been described.^6-8 However, docetaxel has also been implicated in causing acute HSR,^3,4,9 and corticosteroid premedication is recommended. Cremophor EL is not the vehicle for docetaxel (dissolved in Tween 80), which suggests that the taxane moiety is a likely etiologic factor in the incidence of HSR seen with these medications.

In support of this hypothesis, we report a case of a patient who experienced HSR to both agents. A 56-year-old woman underwent surgical debulking at a nearby institution for a uterine mass. This was diagnosed as a poorly differentiated serous papillary adenocarcinoma of the endometrium with bilateral ovarian and peritoneal metastases, and she was prescribed combination chemotherapy with paclitaxel and carboplatin. Before commencement of the paclitaxel infusion, she received standard premedication with dexamethasone, promethazine, and ranitidine. After infusion of 19 mL of paclitaxel (300 mg diluted in 500 mL of dextrose 5% to be administered over 3 hours), the patient experienced sudden onset of dyspnea, wheeze, back pain, and facial flushing. This was followed by a loss of consciousness for approximately 60 seconds, during which time she desaturated as low as 81% (by pulse oximetry) on room air. The paclitaxel infusion was ceased and the patient responded to treatment for an acute HSR. After a period of observation, carboplatin was administered without incident.

After this episode, a decision was made to substitute docetaxel for paclitaxel, and the patient was transferred to our unit for continuation of chemotherapy 3 weeks later. The patient was given the recommended oral corticosteroid premedication, and 30 minutes before commencing the docetaxel, she received additional injections of dexamethasone and promethazine. Five minutes after initiation of the docetaxel infusion (132 mg diluted in 250 mL of sodium chloride 0.9% to be administered over 1 hour), the patient complained of dyspnea and hot flushes, became mildly cyanotic, and desaturated to 90% on room air. The infusion was immediately ceased and the patient was managed appropriately. Again, after a period of observation, carboplatin was administered without incident. She has since completed a third cycle of carboplatin monotherapy without sequelae.

To our knowledge, this case documents the first case of hypersensitivity to docetaxel after a previous HSR to paclitaxel and illustrates the continuing need for caution when administering the taxanes. It also supports the hypothesis that while the Cremophor EL diluent may indeed be responsible for many of the HSRs to paclitaxel, it is probable that there is a distinct subgroup of patients who are hypersensitive to the taxane component of these agents. To confirm this, we are endeavoring to determine whether antitaxane antibodies can be detected and if a suitable assay is available.

REFERENCES

1. Weiss RB, Donehower RC, Wiernik PH, et al: Hypersensitivity reactions from Taxol. J Clin Oncol 8: 1263-1268, 1990[Abstract]

2. Markman M, Kennedy A, Webster K, et al: Paclitaxel-associated hypersensitivity reactions: Experience of the gynecologic oncology program of the Cleveland Clinic Cancer Center. J Clin Oncol 18: 102-105, 2000[Abstract/Free Full Text]

3. Gelman K: The taxoids: Paclitaxel and docetaxel. Lancet 344: 1267-1272, 1994[CrossRef][Medline]

4. Verweij J, Clavel M, Chevalier B. Paclitaxel (Taxol) and docetaxel (Taxotere): Not simply two of a kind. Ann Oncol 5:495-505, 1994

5. Zanotti KM, Markman M: Prevention and management of antineoplastic-induced hypersensitivity reactions. Drug Saf 24: 767-779, 2001[CrossRef][Medline]

6. Lokich J, Anderson N: Paclitaxel hypersensitivity reactions: A role for docetaxel substitution. Ann Oncol 9: 573-574, 1998[Free Full Text]

7. Moon C, Verschraegen CF, Bevers M, et al: Use of docetaxel (Taxotere) in patients with paclitaxel (Taxol) hypersensitivity. Anticancer Drugs 11: 565-568, 2000[CrossRef][Medline]

8. Bernstein B: Docetaxel as an alternative to paclitaxel after acute hypersensitivity reactions. Ann Pharmacotherapy 34: 1332-1335, 2000[Abstract]

9. Cortes JE, Padzur R: Docetaxel. J Clin Oncol 13: 2643-2655, 1995[Abstract]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Denman, J. P. Articles by Abdi, E. A. Search for Related Content PubMed PubMed Citation Articles by Denman, J. P. Articles by Abdi, E. A. Social Bookmarking                            What's this?