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Medline ® Abstracts for References 62-64

of 'Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive disease'

62
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Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions.
AU
Lee CW, Matulonis UA, Castells MC
SO
Gynecol Oncol. 2004;95(2):370.
 
OBJECTIVES: The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12-step desensitization protocol and to characterize the immune mechanism of carboplatin HR.
METHODS: We analyzed 10 consecutive patients who had documented HR to carboplatin and in whom continued treatment with carboplatin was considered advantageous. The patients were treated with carboplatin using a 6-h, 12-step desensitization protocol with a 30-min premedication regimen. Skin tests were performed on five patients.
RESULTS: Ten patients successfully completed 35 planned courses of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n = 3) and third (n = 1) desensitizations but tolerated the re-administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symptoms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequent courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin due to progressive disease. Of the five patients who were skin tested to carboplatin, four had positive wheal and flare reactions. In one patient, the skin test response to carboplatin became negative after desensitization.
CONCLUSION: The 6-h, 12-step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to carboplatin suggest a mast cell/IgE-mediated mechanism. Conversion of the positive skin test to a negative response after desensitization supports antigen-specific mast cell desensitization.
AD
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
PMID
63
TI
Successful desensitization to carboplatin in patients with systemic hypersensitivity reactions.
AU
Broome CB, Schiff RI, Friedman HS
SO
Med Pediatr Oncol. 1996;26(2):105.
 
Carboplatin is the drug of choice for the treatment of nonresectable astrocytomas in children, but patients who are intolerant may require cranial irradiation which is associated with significant morbidity. Hypersensitivity reactions, including urticaria, bronchospasm, and hypotension, have been reported in 1% to 30% of patients treated with carboplatin. Although a few patients have attempted to continue therapy following pretreatment with antihistamines and corticosteroids, most have had recurrent severe reactions and have discontinued therapy. Two children with a history of severe systemic reactions to carboplatin were pretreated with 1 to 2 mg/kg of oral prednisolone the night before and the morning of their infusion. The initial desensitization was carried out in the intensive care unit (ICU) using doses of 1, 2.5, 5, 10, 25, and 50 mg of carboplatin infused at 1 mg/min every 15 minutes. This was well-tolerated and the remainder of the dose was infused at the standard rate of 200 mg/hr. One patient continued to receive infusions in the clinic without any difficulty. The other patient tolerated a second infusion, but during his third he experienced a systemic reaction that required discontinuation of the infusion and treatment with diphenhydramine. Desensitization was repeated in the ICU with pretreatment with prednisolone, diphenhydramine, and ranitidine, starting with 0.1 mg of carboplatin, and increasing more slowly than in the first protocol. This was well-tolerated, and subsequent infusions have been administered beginning with 1 mg doses without adverse effects. Both boys continued therapy with carboplatin; their astrocytomas are stable and they are clinically well. The use of the desensitization protocol enabled them to avoid cranial irradiation and improved their chances for normal neurologic development.
AD
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
PMID
64
TI
Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases.
AU
Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, Laidlaw TM, Legere HJ, Nallamshetty SN, Palis RI, Rao JJ, Berlin ST, Campos SM, Matulonis UA
SO
J Allergy Clin Immunol. 2008;122(3):574.
 
BACKGROUND: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent.
OBJECTIVE: We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol.
METHODS: Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records.
RESULTS: Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective.
CONCLUSIONS: Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs.
AD
Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, USA. mcastells@partners.org
PMID