Hypersensitivity reactions to carboplatin. Report of two patients, review of the literature, and discussion of diagnostic procedures and management

Abstract

Background. Hypersensitivity reactions are rare but sometimes life‐threatening complications of cytostatic combinations containing platinum compounds. Only approximately 40 instances of such hypersensitivity have been reported in association with carboplatin treatment. However, the symptoms probably often are misinterpreted. Method. Signs and symptoms of two patients with severe hypersensitivity reactions to carboplatin are presented. Intracutaneous tests with carboplatin were performed in these two patients and in five control patients receiving carboplatin therapy without unexpected side effects. Results. Both patients had received several cycles of a carboplatin‐containing combination chemotherapy. In both patients, hypersensitivity reactions became manifest for the first time after cumulative doses of 3900 and 5400 mg, respectively. Symptoms included dyspnea, tachycardia, angina pectoris, hypotension, diarrhea, edema, and rash. In both patients, a positive urticarial reaction to intracutaneous carboplatin (diluted 1:10 with normal saline) was observed, whereas five control patients undergoing carboplatin therapy without adverse reaction had negative test results. There were no signs of delayed hypersensitivity. Serum immunoglobulin E levels were normal. Symptoms were ameliorated but not suppressed when one patient was reexposed after pre‐medication with corticosteroids and histamine antagonists. Both patients tolerated high doses of cisplatin without allergic reactions. Conclusions. Although they are rare, hypersensitivity reactions can be serious complications of carboplatin therapy. Simple intracutaneous tests might help to establish the diagnosis to avoid dangerous reexposures. Although the pathogenetic mechanisms are not fully understood, the clinical and experimental findings suggest an anaphylactic type of hypersensitivity, perhaps aggravated to some extent by nonspecific histamine liberation. There seems to be no general cross‐reactivity to cisplatin.

Life-threatening carboplatin hypersensitivity during conditioning for autologous PBSC transplantation: successful rechallenge after desensitization

“…5 Severity of reactions ranged from transient and mild reactions resembling common side-effects of anti-cancer chemotherapy or nearfatal anaphylaxis. 1,5 However, massive pulmonary infiltrations with hemoptysis and hypoxia resulting in transient myocardial ischemia as seen in this case have not been reported to date. Most cases of hypersensitivity to carboplatin have occurred in patients receiving repeated cycles of carboplatin, denoting the slow development of hypersensitivity in general.…”

“…1,[6][7][8] The mechanism of hypersensitivity in this patient seemed to be the latter as she had no previous sensitization to either carboplatin or cisplatin.…”

“…[1][2][3] The clinical features of allergic reactions to carboplatin have resembled the symptoms of a histamine-induced type I hypersensitivity reaction, usually developing soon after the onset of an infusion. Symptoms have included respiratory (wheezing, dyspnea), gastrointestinal (abdominal cramps, diarrhea), and dermatologic symptoms (pruritus, urticaria, facial erythema, and swelling).…”

“…Although type I hypersensitivity has been reported in 1% to 20% of patients who receive cisplatin, there are few reports of similar reactions in patients receiving repeated cycles of carboplatin therapy. 1,2 To our knowledge, there have been no reported cases of life-threatening carboplatin hypersensitivity in the transplant setting.…”

“…Most of the patients reported who have had allergic reactions to carboplatin were unable to tolerate further treatment with it despite heavy premedication with steroids and antihistaminics. 1,3 In our case, however, carboplatin was re-introduced successfully as a conditioning regimen after a course of desensitization.…”