Paclitaxel


A member of a new class of antineoplastic agents (taxanes), paclitaxel is a natural diterpene product, isolated from the bark of Taxus brevifolia.
 
Clinically active in ovarian, breast and non-small lung cancer.
 
Incidence
Severe reactions: 2%.
 
Hypersensitivity reactions: > 10%.
 
Clinical manifestations
Bronchospasm, dyspnea (81%).
 
Urticaria, erythematous rash (74%).
 
Hypotension (41%).
 
Angioedema (19%).
 
Pneumonitis (in previously irradiated patients).
 
Diagnostic methods
Basophil histamine release: non IgE-mediated response.
 
Mechanisms
The vehicle (cremophor EL + ethanol) is likely to be responsible.
 
Management
Premedication is effective. Numerous prophylactic regimens have been published:
 
  • 1° 20 mg dexamethasone orally 12 hours and 6 hours before paclitaxel, and 20 mg I.V just before treatment + 50 mg diphenhydramine orally 12 hours and 6 hours before paclitaxel, and 50 mg I.V just before treatment + 25 mg ephedrine sulfate orally one hour before paclitaxel (if possible).
  • 2° 5 to 20 mg dexamethasone I.V + 50 mg diphenhydramine I.V + 300 mg cimetidine or 50 mg ranitidine I.V 30 minutes before paclitaxel.
  • 3° 20 mg dexamethasone I.V just before paclitaxel + 50 mg orphenadrine I.M, and 300 mg cimetidine I.V one hour before paclitaxel.
Desensitization:
 
1/100000 (1, 2, 4, 8 ml) to 1 ml undiluted solution, then continuous infusion.
 
Alternative formulations of paclitaxel:
 
  • polyethylene glycol (decreases the antitumor activity of taxol)
  • cyclodextrins (renal and hemolytic toxicity)
  • polyvinylpyrrolidone nanoparticles (improvement in antitumor efficacy)
  • phospholipid suspensions: liposomes (increased efficacy)
  • prodrugs.

Clinical efficacy needs to be established. 

References

  1. Szebeni J, Muggia F.M, Alving C.R, "Complement activation by cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study", J. Natl. Cancer. Inst., 1998; 90 (4): 300-6
  2. Bookman M.A, Kloth D.D, Kover P.E, Smolinski S, Ozols R.F, "Short-course intravenous prophylaxis for paclitaxel-related hypersensitivity reactions", Ann. Oncol., 1997; 8 (6): 611-4
  3. Meerum-Terwogt J.M, Nuijen B, Ten Bokkel Huinink W.W, Beijnen J.H, "Alternative formulations of paclitaxel", Cancer Treat. Rev., 1997; 23 (2): 87-95
  4. Essayan D.M, Kagey-Sobotka A, Colarusso P.J, Lichtenstein L.M, Ozols R.F, King E.D, "Successful parenteral desensitization to paclitaxel", J. Allergy. Clin. Immunol, 1996; 97: 42-6
  5. Boehm D.K, Maksymiuk A.W, "Paclitaxel premedication regimens (letter)", J. Natl. Cancer. Inst., 1996; 88 (7): 463-5
  6. Gennari A, Salvadori B, Tognoni A, Conte P.F, "Rapid intravenous premedication with dexamethasone prevents hypersensitivity reactions to paclitaxel (letter), Ann. Oncol., 1996; 7 (9): 978-9
  7. Weiss R.B, Donehower R.C, Wiernik P.H, Ohnuma T, Gralla R.J, Trump D.L, Baker J.R Jr, Van Echo D.A, Von Hoff D.D, Leyland-Jones B, "Hypersensitivity reactions from taxol", J. Clin. Oncol., 1990; 8 (7): 1263-8

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