Desensitization treatment with cisplatin after carboplatin hypersensitivity reaction in gynecologic cancer

Department of Obstetrics and Gynecology, Oe Kyodo Hospital, Tokushima, Japan The Journal of Medical Investigation Vol. 57 February 2010

Akiko Abe, Hiroshi Ikawa, and Saki Ikawa

Introduction
the platinum-based chemotherapy is the standard carboplatin:- less neuro-, nephro-, gastrointestinal
toxicity - more myelosuppression

the use of carboplatin has become greater, unfavorable side effect more frequently: hypersensitivity reactions (HR), incidence of HR with carboplatin increases with repeated drug exposure (6-21 courses of treatment) serious problem when an extended number of courses are attempted

Introduction
proposed preventive procedures:
premedication with antihistamines or corticosteroids substitution with a different platinum salt desensitization protocol

Patients
retrospective evaluate: 2001-2007 73 patients treated with carboplatin-based chemotherapy identified 17 patients (22%):
cervical (n=2), endometrial (n=4), ovarian (n=11)

Patients

Patients

Patients
number of prior platinum treatments before the first HR observation: 5-27 all reactions during platinum infusion no patients developed delayed reactions none of the eight patients with severe HR was rechallenged with platinum

Patients
3 patients - mild HR - rechallenged with carboplatin after providing informed consent
without desensitization, rechallenge was not successful - all experienced HR recurrence. symptoms did not occur immediately after rechallenge, but at a mean of 40 min (range 30 to 60 min)

other 3 of 17 patients - with mild HR - treated successfully with a desensitization protocol, substituting cisplatin (60 mg/m2) for carboplatin

Patients

Desensitization protocol
1. day

Premedication:
Promethazine 50mg Dexamethasone 20mg Ranitidine 50mg

administered 30 min before the initiation

Desensitization protocol
1. day

paclitaxel (175 mg/m2) infusion cisplatin 60 mg/m2

60 g/m2 in 100 ml saline (1 : 1000 dilution of the final therapeutic dose) 100 ml / 60 min 600 g/m2 in 100 ml saline (1 : 100 dilution of the final therapeutic dose) 100 ml / 60 min 6000 g/m2 in 100 ml saline (1 : 10 dilution of the final therapeutic dose) 100 ml / 60 min

infusion was temporarily interrupted

Desensitization protocol
2. day

cisplatin 60 mg/m2
6000 g/m2 in 100 ml saline (1 : 10 dilution of the final therapeutic dose) 100 ml / 60 min remainder of the cisplatin at the therapeutic dose (60mg 12,66mg = 47,34mg/m2) over 8 hours

Discussion
mechanism of HR to carboplatin remains unclear (classified as type 1 IgE-mediated allergy ?) skin test is useful for identifying patients for reappearance of an allergic reaction prolonged use of carboplatin increases the incidence of HR. (27% of patients who had received more than seven courses)

Discussion
once HR is established, rechallenge should not be attempted because the cases very likely will experience anaphylaxis. substituting cisplatin for carboplatin after HR development is a good strategy if continuation of platinum-based chemotherapy is highly desirable. method for preventing HR to carboplatin: desensitization protocol by gradual re-introduction of small amounts of drug antigens to full therapeutic doses.

Conclusion
usefulness and effectiveness of the desensitization protocol for the continuation of platinum treatment in patients who had undergone an extended number of carboplatin treatments. the aim of this report is to draws the attention for a possibility to continue succesfully the platinum based therapy after the hypersensitivity reaction.

Thank you