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Page 2 of 8 Burches et al. J Cancer Metastasis Treat 2019;5:63 I http://dx.doi.org/10.20517/2394-4722.2019.012

Conclusion: LRDP with carboplatin is a feasible and safe protocol in patients with previous infusion reaction to
carboplatin. The protocol might allow a safe administration of drugs, that are beneficial for the management of patients,
after certain types of hypersensitivity reactions, and it is indicated in cases in which there are no reasonable therapeutic
alternatives.

Keywords: Drug allergy, hypersensitivity, desensitization, rapid protocol, logarithmic model, carboplatin

INTRODUCTION
Platinum-based chemotherapeutic agents have been used for the treatment of numerous solid tumors
affecting several locations (such as breast, ovarian, endometrial, lung, and gastrointestinal tract). As a
[1,2]
result of its extended use, platinum compounds have produced an increased number of reactions .
Hypersensitivity reactions are much more frequent with platins than with other drugs. Reactions to
carboplatin are a frequent adverse event with an overall incidence of 1%-44% supposing a challenge in the
management of ovarian cancer.

In ovarian cancer, platinum-responsiveness have been a classical prognostic factor. Reintroduction of
platinum-containing schedules in patients with platinum-responsiveness relapse (> 6 months of interval) is
[3-4]
widely recommended . Carboplatin has shown in a randomized trial similar survival than cisplatin but
[5]
with better safety profile and quality of life . Since then carboplatin-containing chemotherapy has been
considered standard and, as a consequence, relapsed ovarian cancer patients are frequently exposed to an
important number of carboplatin infusions.

Positive carboplatin skin tests and the presentation pattern of these reactions suggest that type I pathway
immunological mechanisms are involved. Moreover, platinum-specific IgE can be also found in serum
among exposed refinery workers and it supports the theory of type IgE-mediated reaction. Furthermore,
clinical symptoms related to a reaction to carboplatin range from a mild rash to severe anaphylaxis; thus,
[1]
different types of immunologic hypersensitivity seem to be implicated .

The fact that the reintroduction of platinum is a major issue in platinum-sensitive patients has
prompted the development of desensitization protocols. Rapid desensitization is a procedure for gradual
reintroduction of drug at a low dose by dissolving it at a low and intermediate concentration, until reaching
the target dose. It allows a safe administration of medications that are beneficial for the management of
patients after certain types of hypersensitivity reactions, and it is indicated in cases in which there are no
reasonable therapeutic alternatives.

We have performed a retrospective study with the aim of assessing the effectiveness and safety of a
logarithm (geometric series) rapid desensitization protocol (LRDP) of carboplatin in patients with
platinum-sensitive ovarian relapse that had a previous allergic reaction during carboplatin infusion.

METHODS
Design
This is a pivotal study with the objective of assessing effectiveness and safety of LRDP, in terms of
number and severity of infusion reactions, in patients with previous reactions to carboplatin exposure
and proportion of completely administered carboplatin-containing schedules. A retrospective review
of the clinical chart of patients diagnosed with ovarian cancer in our institution since January 2007 was
performed. Data extracted from the clinical chart included: (1) diagnosis, pathological variables and
demographic data; (2) data from initial infusion reaction; (3) skin tests; and (4) data from the outcome
during LPRD and type of reactions occurring during this protocol.