Docetaxel


Docetaxel, the new chemotherapeutic agent (taxoids) derived from the needles of the European yew (Taxus baccata); shows significant antitumor activity in phase II trials of ovarian, breast and non small cells lung cancer.
 
Incidence
Cutaneous manifestations (erythema, pruritus, dry skin, macular eruptions, swelling, burning, desquamation): 64.3%. Grade III: 6.4%; grade IV: 1.7%.
 
Fever: 35.8%. Grade III: 2.8%; grade IV: 0.2%.
 
Hypersensitivity reactions: 31.3 % (usually occurring in the first or second course).
 
Mild: pruritus, flushing, rash, fever, chills.
 
Severe: hypotension, dyspnea, bronchospasm, general urticaria or angioedema.
 
Grade III: 6.7%; grade IV: 0.6%.
 
Clinical manifestations
General: hypotension, fever, chills.
 
Cutaneous: erythrodysesthesia, solitary erythematous to edematous plaque in the infusionarm proximal to the site of infusion, pruritus, urticaria, angioedema, flushing.
 
Respiratory: dyspnea, bronchospasm.
 
Diagnostic methods
Skin biopsy (erythrodysesthesia): epidermal dysmaturation with necrotic keratinocytes or sparse superficial perivascular lymphocytic infiltration with eosinophils, focal vacuolar alteration or plain perivascular lymphocytic inflammation.
 
Mechanisms
Non-specific release of vasoactive mediators following mast-cell degranulation is likely.
 
Management
The usefulness of premedication with antihistamines and corticosteroids is controversial.
 
Oral pretreatment 12 hours and 3 hours before infusion of docetaxel with 32 mg of methyprednisolone, 10 mg of cetirizine and 1 mg of ketotifen limits the development of acute hypersensitivity reactions (28% -> 7.7%).
 
Classical prophylactic medication: dexamethasone 8 mg 13 hours, 7 hours, 1 hour before the administration of docetaxel; clemastine 1 mg 13 hours, 7 hours, 1 hour, before the administration of docetaxel; followed by dexamethasone 8 mg p.o. twice daily for 3 days.
 
Sodium cromoglycate (400 mg orally x 4 daily) could be an alternative to corticosteroids and conventional antihistamines in the treatment of taxoid-induced acute hypersensitivity reactions.
 
Skin toxicity is not prevented by corticosteroids and antihistamines. Treatment with an ointment of glycerin and chlorhexidine is simple, and improves the condition in most patients.

References

  1. Westermann A.M, ten Bokkel Huinink W.W, Rodenhuis S, "Successful docetaxel re-challenge with cromoglycate after major sensitivity reactions", Ann. Oncol., 1996; 7 (1): 104
  2. Cortes J.E, Pazdur R, "Docetaxel", J. Clin. Oncol., 1995; 13 (10): 2643-55
  3. Zimmermann G.C, Keeling J.H, Burris H.A, Cook G, Irvin R, Kuhn J, Mc Collough M.L, Von Hoff D.D, "Acute cutaneous reactions to docetaxel, a new chemotherapeutic agent", Arch. Dermatol., 1995; 131 (2): 202-6
  4. Schrijvers D, Wanders J, Dirix L, Prove A, Vonck I, van Oosterom A, Kaye S, "Coping with toxicities of docetaxel (Taxotere)", Ann. Oncol., 1993; 4 (7): 610-11

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