Carboplatin


Mainstay therapy in ovarian and testicular carcinoma but also in brain tumors in children (pilocytic astrocytoma).
 
Incidence
Unusual (< 8% of patients).
 
Increase with the number of courses in adults (6% at cycle 6 to 67% by cycle 10) with ovarian carcinoma.
 
10 of 150 children with brain tumors.
 
Risk factors
Occupational exposure to platinum salts(?)
 
Clinical manifestations
General: anaphylactic shock.
 
Cutaneous: pruritus, urticaria, diffuse erythema.
 
Respiratory: dyspnea, bronchospasm, cyanosis.
 
Digestive: vomiting.
 
Diagnostic methods
Cutaneous testing
 
Intradermal skin-tests positive at 0,1 mg/ ml and 1 mg/ ml in a few patients.
 
No specific IgE found.
 
Mechanisms
IgE-mediated hypersensitivity in some cases (platinum is a tetravalent inorganic molecule that readily complexes with proteins to form antigens).
 
Direct histamine release.
 
Management
Pre-treatment with corticosteroids and antihistamines (sometimes ineffective in preventing IgE-mediated reactions).
 
Desensitization.
 
Many protocols have been reported:
 
 
 
In children:
 
"rush" protocol:
Premedication with prednisolone 12 h and 1 h before, diphenydramine 30 minute before and ranitidine 30 minute before.
 
Then: 1 - 2.5 - 5 - 10 - 25 and 50 mg of carboplatin infused at 1 mg/min every 15 minutes. The remainder of the dose at 200 mg/hr.
 
"slow" protocol:
0.1 - 0.2 - 0.5 - 1 - 2 - 3 - 4 - 5 - 7.5 - 10 and 15 mg at 1 mg/min every 15 minutes.
 
Then: 100 mg/ hr for one hour then remainder of the dose at 200 mg/ hr.
 
 
 
In adults:
 
"rush" protocol (4 hours):
 
350 mg/ m2 carboplatin in 100 ml aqueous dextrose solution (D5W)
 
0.1 ml - 1 ml - 10 ml diluted in 100 ml D5W over one hour each. The remainder of the dose over one hour.
 
 
"slow" protocol (81 hours): 
 
0.4 mg carboplatin/150 ml over 1.5 hour.
 
4 mg carboplatin/150 ml over 15 hours.
 
40 mg carboplatin/150 ml over 15 hours.
 
355 mg carboplatin/500 ml over 50 hours.

References

  1. Broome C.B, Schiff R.I, Friedman H.S, "Successful desensitization to carboplatin in patients with systemic hypersensitivity reactions", Med. Pediatr. Oncol., 1996; 26 (2): 105-10
  2. Goldberg A, Confino-Cohen R, Fishman A, Beyth Y, Altaras M, "A modified prolonged desensitization protocol in carboplatin allergy", J. Allergy. Clin. Immunol., 1996; 98: 841-3
  3. Windom H.H, Mac-Guire W, Hamilton R.G, Adkinson Jr N.F, "Anaphylaxis to carboplatin. A new platinum chemotherapeutic agent", J. Allergy. Clin. Immunol., 1992; 90: 681-3

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.