Procarbazine


Cytostatic agent derived from methylhydralazine. Mainly used in the treatment of lymphoma and brain tumors.
 
Incidence
Severe allergic reactions: 2%, severe toxic effects: 2%, life-threatening allergic reactions: 1% in Hodgkin’s disease.
 
Much higher (25%) in patients with brain tumors.
 
Risk factors
Brain tumors, especially when anticonvulsant therapy is used.
 
Clinical manifestations
General: fever.
 
Respiratory: cough, dyspnea, acute pulmonary infiltrates, pleural effusion.
 
Cutaneous: pruritus, urticaria, maculopapular rash (+++), angioedema, fixed drugeruption, toxic epidermal necrolysis.
 
Diagnostic methods
No in vivo or in vitro method is currently available for diagnosis other than re-challenge (which is hazardous: life-threatening pneumonitis published).
 
Mechanisms
Classical complement pathway activation is possible.
 
Procarbazine oxidation to a reactive intermediate is enhanced by phenobarbital.
 
Management
Avoidance.
 
Use non enzyme-inducing anticonvulsants.
 
Corticosteroids are useful in the management of respiratory manifestations.

References

  1. Lehmann D.F, Hurteau T.E, Newman N, Coyle T.E, "Anticonvulsant usage is associated with an increased risk of procarbazine hypersensitivity reactions in patients with brain tumors", Clin. Pharmacol. Ther., 1997; 62 (2): 225-9
  2. Coyle T, Bushunow P, Winfield J, Wright J, Graziano S, "Hypersensitivity reactions to procarbazine with mechlorethamine, vincristine, and procarbazine chemotherapy in the treatment of glioma", Cancer, 1992; 69 (10): 2532-40
  3. Brooks B.J Jr, Hendler M.B, Alvarez S, Ancalmo N, Grinton S.F, "Delayed life-threatening pneumonitis secondary to procarbazine", Am. J. Clin. Oncol., 1990; 13 (3): 244-6
  4. Glovsky M.N, Braunwald J, Opelz G, Alenty A, "Hypersensitivity to procarbazine associated with angioedema, urticaria and low serum complement activity", J. Allergy. Clin. Immunol., 1976; 57 (2): 134-40

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