Cisplatin


Cytostatic agent able to inhibit DNA synthesis selectively and specifically. Most active agent in germ-cell tumors and osteogenic carcinoma.
 
Incidence
Common in the 1970’s studies: 6 to 14% (six or more doses of cisplatin).
 
Far less frequent in the 1980’s: only 3 or 4 cisplatin courses in testicular carcinoma; and common use of diphenydramine and dexamethasone in emesis prevention.
 
Risk factors
Concurrent use of other drugs (bleomycin, actinomycin, vinblastine, cyclophosphamide).
 
Intravesical use: incidence 10 to 25% (especially if > 8 courses).
 
Intraperitoneal use: if large doses and high infusion time ratio (>2,2).
 
Occupational exposure to platinum salts(?).
 
Clinical manifestations
General: anaphylactic shock (deaths reported).
 
Cutaneous (most common): pruritus, urticaria, rash, flush.
 
Respiratory: dyspnea, bronchospasm.
 
Digestive: vomiting.
 
Hematological: hemolytic anemia (or false positive direct antiglobulin test).
 
Diagnostic methods
Cutaneous testing.
 
Prick-test: 0,1 mg/ ml
 
Intradermal-test: 0,001 mg/ ml; 0,01 mg/ ml; 0,1 mg/ ml.
 
Few patients positive to I.D. 0,1 mg/ ml.
 
Histamine release.
 
One case with positive histamine release test.
 
Mechanisms
IgE-mediated hypersensitivity in some cases (cisplatin acts as a hapten bound to serum proteins).
 
Direct release of vasoactive substances.
 
Management
Pretreatment with corticosteroids and antihistamines (sometimes ineffective in preventing IgE-mediated reactions).
 
Desensitization: a few cases reported.
 
After premedication with hydroxyzine and methylprednisolone, gradual increase of doses from 1 mg to 80 mg at 30 min intervals.
 
Cross-reactivity with other platin derivatives (carboplatin, iproplatin and DACPP) is likely.

References

  1. Hebert M.E, Blivin J.L., Kessler J, Soper J.T, Oleson J.R.,"Anaphylactoid reactions with intraperitoneal cisplatin", Ann. Pharmacother., 1995; 29:
    260-3
  2. Goldberg A, Altaras M.M., Mekori Y.A, Beyth Y, Confino-Cohen R., "Anaphylaxis to cisplatin: diagnosis and value of pretreatment in prevention of recurrent allergic reactions". Ann. Allergy., 1994; 73: 271-2
  3. Ter-Schiphorst C, Bousquet J, Menardo J.L, Piquemal M, Bataille A, Michel F.B., "Desensibilisation spécifique au cis-dichloro-diamino-platinum (D.D.P:) chez un malade allergique", Presse. Med., 1986; 15 (26): 1242.

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