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Classification of the initial reaction bored three aspects: characteristics, severity and timing (time interval
between drug administration and the reaction).

Characteristics of clinical symptoms associated with the initial hypersensitivity reactions were categorized
by organ system involvement. Cutaneous symptoms (oedema of the face and hands, flushing, pruritus,
urticaria or angioedema), respiratory symptoms (dyspnea or wheezing or oxygen desaturation, coughing,
nasal congestion), abdominal symptoms (nausea, emesis/vomiting, diarrhea, or abdominal pain), laryngeal
angioedema/throat tightness, or cardiovascular symptoms (chest pain, hypotension, hypertension, or
tachycardia), neurological/muscular (vision disturbances, weakness, unusual taste, hallucinations, or
[1,2]
neurological compromise) according to previous publications .
Hypersensitivity severity: A mild rash may be the first manifestation of reactions. Hypersensitivity reactions
were classified as mild (reactions limited to the skin), moderate (features suggesting respiratory - dyspnea,
wheeze -, cardiovascular - dizziness, diaphoresis, chest tightness - or gastrointestinal involvement - nausea,
vomiting, abdominal pain -) or severe (hypoxia, hypotension and neurological compromise - confusion,
[6]
collapse or incontinence -) according to the scale proposed by Brown .
As for the timing of reaction, hypersensitivity reactions were categorized as immediate or delayed.
Immediate reactions were turned up usually during drug administration while delaying reactions were
presented after drug administration.

This retrospective study was approved by the local Ethics Committee of Hospital Clinico Universitario of
Valencia (resolution number 320) in November 2016.

Patients
Patients included had a histological diagnosis of high-grade ovarian carcinoma and a platinum-sensitive
relapsed defined as recurrence after at least 6 months of platinum-free interval. Being considered candidates
for the LRDP, patients must have presented a hypersensitivity reaction during carboplatin infusion in a
[7]
previous cycle. Carboplatin hypersensitivity is a late event . Consistent with these studies, all reactions in
our population occurred after re-exposure to at least seven previous cycles of carboplatin.

In all cases, the initial infusion reaction had been evaluated and managed by emergency staff of the
outpatient Oncology department.

Exclusion criteria were an impossibility to understand or to sign informed consent or lack of expected
benefit with the reintroduction of carboplatin according to the clinician’s opinion.

All patients with a previous type I reaction underwent a skin test with carboplatin before LRDP. Skin
testing was performed at least 4 weeks after the initial reaction to minimize the likelihood of false negative
results. Drug was diluted further in water with 5% dextrose for testing. For prick test, a drop of carboplatin
(10 mg/mL) was applied to the volar surface of the forearm followed by pricking. For intradermal injections
0.03 mL (of a 1:100 dilution followed, if the result was negative, by an 1:10 dilution). A positive reaction
was defined as a wheal with a diameter at least 3 mm large that produced by a negative control. Histamine
[1,2]
prick (10 mg/mL) was used as a positive control .
Informed consent was obtained from each patient before skin testing and desensitization procedures.

Treatment
Before (24-72 h previous) administration of LRDP, a blood test including creatinine and hemogram was
performed. Patients were then seen in the outpatient unit of Medical Oncology. Treatment was only