Desensibilizare carboplatin bemutato

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Desensitization treatment

with cisplatin aftercarboplatin hypersensitivity reactionin gynecologic cancer

Akiko Abe, Hiroshi Ikawa, and Saki IkawaDepartment of Obstetrics and Gynecology, Oe Kyodo

Hospital, Tokushima, Japan

The Journal of Medical Investigation

Vol. 57 February 2010


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Introduction

the platinum-based chemotherapy is the standard

carboplatin:- less neuro-, nephro-, gastrointestinaltoxicity

- 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


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Introduction

proposed preventive procedures: premedication with antihistamines or corticosteroids

substitution with a different platinum salt

desensitization protocol


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Patients

retrospective evaluate: 2001-2007

73 patients treated with carboplatin-basedchemotherapy

identified 17 patients (22%): cervical (n=2),

endometrial (n=4),

ovarian (n=11)


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Patients


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Patients


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Patients

number of prior platinum treatments before thefirst HR observation: 5-27

all reactions during platinum infusion

no patients developed delayed reactions

none of the eight patients with severe HR wasrechallenged with platinum


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Patients

3 patients - mild HR - rechallenged with carboplatinafter providing informed consent without desensitization, rechallenge was not successful - all

experienced HR recurrence.

symptoms did not occur immediately after rechallenge, but ata mean of 40 min (range 30 to 60 min)

other 3 of 17 patients - with mild HR - treatedsuccessfully with a desensitization protocol,

substituting cisplatin (60 mg/m2) for carboplatin


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Patients


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Desensitization protocol

1. day

Premedication: Promethazine 50mg

Dexamethasone 20mg

Ranitidine 50mg

administered 30 min before the initiation


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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


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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


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Discussion

mechanism of HR to carboplatin remains unclear(classified as type 1 IgE-mediated allergy ?)

skin test is useful for identifyingpatients for

reappearance of anallergic reaction prolonged use of carboplatin increases the incidence

of HR. (27% of patients who had received more thanseven courses)


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Discussion

once HR is established, rechallenge should not beattempted because the cases very likely willexperience anaphylaxis.

substituting cisplatin for carboplatin after HRdevelopment is a good strategy if continuation ofplatinum-based chemotherapy is highly desirable.

method for preventing HR to carboplatin:

desensitization protocol by gradual re-introductionof small amounts of drug antigens to full therapeuticdoses.


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Conclusion

usefulness and effectiveness of the desensitizationprotocol for the continuation of platinum treatmentin 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 basedtherapy after the hypersensitivity reaction.


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Thank you

Desensibilizare carboplatin bemutato

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