All
chemotherapy agents can cause
hypersensitivity reactions, which have limited the used of critical drugs in very sick patients for fear of inducing a more severe reaction and possibly death. The choice of an alternative
chemotherapy regimen is often limited by
tumor sensitivity and, because of the increasing number of cancer survivors, exposure to multiple courses of the same or similar
chemotherapy agents. Increased exposures lead to sensitization and to
hypersensitivity reactions in an increasing patient population. The need to offer first line
therapy after
cancer recurrence has spurred the clinical development of rapid desensitizations, which allow patients to be treated with medications to which they have presented
hypersensitivity reactions. Desensitization protocols are available to treat
hypersensitivity reactions to most
chemotherapy agents including taxenes, platinums,
doxorubicin,
monoclonal antibodies and others, by gradual re-introduction of small amounts of
drug antigens up to full therapeutic doses. Candidate patients include those who present mild to severe
type I hypersensitivity, mast cell/
IgE dependent, reactions during the
chemotherapy infusion or shortly after. Symptoms include
pruritus,
flushing,
urticaria,
angioedema, respiratory and gastrointestinal distress, changes in blood pressure including
hypotension, and
shock with
anaphylaxis. Associated musculoskeletal symptoms and
pain can be present in patients reacting to taxenes as in
anaphylactoid reactions, in which mast cell/
IgE mechanisms cannot be demonstrated. There is now strong evidence that
anaphylactoid reactions are amendable to treatment with the same rapid desensitization protocols as for
type I hypersensitivity reactions. Initial rapid desensitizations should only be performed in settings with one on one nurse-patient care and where
resuscitation personnel and resources are readily available. Temporary tolerization is achieved in a few hours. After the first desensitization, standard protocols are available for safe, repeated desensitizations in outpatient settings with similar conditions, which not only provides flexibility, but allows patients to remain in clinical studies. Breakthrough symptoms are less severe than the initial
hypersensitivity reaction in all series reviewed, and deaths have not been reported. The aim of this review is to familiarize the medical community with the type of
hypersensitivity reactions amendable to rapid desensitization and to review protocols for
chemotherapy desensitization that can be used for most
chemotherapy agents. Few studies have measured the
cancer response to the
chemotherapy agents delivered through rapid desensitizations. One patient population in which 26 patients were desensitized to
carboplatin and 16 to
paclitaxel had similar rates of remission as for non-desensitized patients. Education of nurses, pharmacists, oncology and
allergy specialists will lead to the universal use of rapid desensitization protocols for all
cancer patients with
hypersensitivity reactions to
chemotherapy agents. Basic research is needed to uncover the cellular and molecular mechanisms underlying the temporary tolerization induced by rapid desensitization, so that pharmacological interventions can improve its safety and efficacy.