Carboplatin Hypersensitivity Reactions: A Single Institution Experience

Abstract

Carboplatin-related hypersensitivity reactions, frequently encountered in the heavily pretreated subpopulation of patients with gynecologic malignancies, can be severe and even potentially lethal-precluding these patients from an effective salvage treatment. We describe our experience in the management of such reactions and the application of a pretreatment protocol with corticosteroids, antihistamines and a slow infusion rate in order to safely re-administer carboplatin to the above patients. From 1998 to 2004, twenty patients developed an allergic reaction to carboplatin. Sixteen of them (80%) suffered from ovarian cancer. Upon resolution of the acute reaction, thirteen patients were pretreated according to our protocol and were re-exposed to carboplatin. Fifteen patients experienced the reaction during second-line carboplatin-based treatment and 5 patients after 3 or more regimens. Fifteen of the reactions (75%) were severe. Thirteen patients were re-treated with carboplatin after the application of our protocol, all of them successfully, even though 10 patients (77%) experienced minor symptoms during subsequent courses. On the contrary, only one of the 6 patients who were re-treated without the application of the protocol was able to receive further platinum-based treatment. In conclusion, pretreatment with corticosteroids, antihistamines and a slower infusion rate may make re-treatment possible in patients having experienced hypersensitivity to carboplatin.

Incidence of Carboplatin-Related Hypersensitivity Reactions in Japanese Patients With Gynecologic Malignancies

“…The median number of cycles before the first carboplatin HSR was 7 to 10 in the USA, 1,4,13Y18 9 in Germany, 11 9 in Israel, 12 and the HSRs were very rarely seen before the fifth or sixth cycle. 19 Hypersensitivity reactions were observed after a mean of 6 cycles in women receiving first-line carboplatin in the USA.…”

“…2,3,28 An interesting management procedure in the case of allergic reactions is the aggressive treatment of acute reaction after discontinuation of the offending agent and reinitiation of this agent as soon as symptoms resolve. 9 The success of this procedure is probably because of the underlying mechanism of the allergic reaction and forms the basis for successful administration after applying a desensitization protocol. 15 In the case of carboplatin, with immunoglobulin E antibodies implicated in the reaction mechanism, intensive suppression of the immune response through blocking H1 and H2 receptors by premedication results in a reduced immunologic response.…”

“…Moreover, a slow rate of infusion up to 2 hours and the dilution of carboplatin not exceeding 1 mg/mL seem to contribute to better tolerance to the rechallenge. 9 In the current study, we temporarily interrupted carboplatin infusion when mild reactions appeared and used the dilution and slow infusion protocol to safely readminister the agent with antihistamines and corticosteroids after a previous report. 9 Because the optimal management of patients who develop carboplatin HSRs remains undefined, further considerations are needed such as alterations in the schedule or infusion times or administering additional premedications to prevent severe reactions.…”

“…9 In the current study, we temporarily interrupted carboplatin infusion when mild reactions appeared and used the dilution and slow infusion protocol to safely readminister the agent with antihistamines and corticosteroids after a previous report. 9 Because the optimal management of patients who develop carboplatin HSRs remains undefined, further considerations are needed such as alterations in the schedule or infusion times or administering additional premedications to prevent severe reactions. One possible method may be to switch intravenous infusion to intraperitoneal (IP) administration in advanced ovarian cancer patients because the 4 cases of severe HSRs in our study manifested during third-line carboplatin treatment of stage IIIc-IV ovarian cancer.…”

The prophylactic conversion to an extended infusion schedule and use of premedication to prevent hypersensitivity reactions in ovarian cancer patients during carboplatin retreatment

“…Patients are routinely premedicated with steroids the night before and morning of taxane treatment to minimize the risk of paclitaxel allergy. It is unclear from the literature, and also from the results of this retrospective study, whether aggressive premedication alone with ranitidine, diphenhydramine, and corticosteroids administered intravenously immediately prior to chemotherapy combined with oral corticosteroids taken by the patient at home the night before and morning of treatment might be sufficient to reduce the incidence of carboplatin HSRs [24]. …”