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Page 4 of 8 Burches et al. J Cancer Metastasis Treat 2019;5:63 I http://dx.doi.org/10.20517/2394-4722.2019.012

administered if neutrophils count was ≥ 1500 and platelet count ≥ 100,000. A total dose of carboplatin was
always calculated according to the most recent creatinine levels.

According to the severity of the previous reaction and the results of the skin test, the first cycle of the LRDP
was administered under an intensive monitoring in an Intensive Care Unit or under a lighter monitoring
surveillance in beds of the Oncology Department inpatient area.

A standard premedication with corticosteroids and antagonists of histamine receptors was administered
before desensitization to all patients. Metoclopramide hydrochloryde 10 mg and dexamethasone 8 mg were
given intravenously before initiation of LRDP as standard emesis prophylaxis. Histamine blockade (H1/H2)
was performed with 5 mg of parenteral dexchlorpheniramine (5 mg/mL amp) and ranitidine (50 mg i.v.).

The management of reaction during desensitization was intended to block the effects of mast cell
mediators, including histamine, prostaglandins and leukotrienes. If symptoms of a hypersensitivity reaction
was developed during the desensitization procedure, the infusion was stopped.

In case of a mild reaction, 50 mg of parenteral dexchlorpheniramine (5 mg/mL) was administered. For
severe or recurrent reactions, 40 mg of parenteral methylprednisolone (sodium succinate 0.5 mg/kg
intravenously) and epinephrine 0.3 mL (1 mg/mL) were also added. Bronchoespasm and throat tightness
was treated with inhaled B-agonists. Flushing was treated with aspirin and montelukast. Once symptoms
have resolved, the protocol was resumed and the infusion was restarted at the point where the reaction
occurred. All desensitization procedures were prescribed and supervised by the allergy and oncology
departments and were conducted under physician supervision.

This 13-step LRDP combined gradual increases in the rate of infusion and concentration of carboplatin,
administering the total dose over 5 h [Table 1].

The total target dose of carboplatin was calculated using the Cockrott-Gault’s formulation based on the
area under the curve with a creatinine level obtained in no more than 24 h previous to the LRDP. Three
different solutions A, B and C were employed with a total volume of 50 mL, 100 mL and 500 mL of water
with 5% dextrose respectively and delivered in 13 consecutive steps. The concentrations of the solutions
were 0.1 mg/mL for infusion A, 1 mg/mL for infusion B and 2 mg/mL for infusion C. Solution A was used
for steps 1 to 7, solution B for steps 8 to 11 and solution C for steps 12 and 13. The total dose of carboplatin
administered in the last step was calculated by subtracting the cumulative dose given in the steps 1-12 from
the total target dose.

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The initial dose was approximately in the order of a 10 times lower (in a rank of 0.2-3 × 10 ) that the
target dose and each step deliver twice the dose of the previous step. All step concentrations are arranged
in a geometric series with a factor two. The first term of the series is 1/32 and the common ratio is 2
(1/32, 1/16, 1/8, 1/4, 1/2, 1, 2, .......). The rate of the infusion was adjusted every 15 min. The final step 13
maintained a constant rate of infusion in order to deliver the remainder of the total carboplatin dose.

RESULTS
From February 2011 to November 2014, 4 patients with platinum-sensitive recurrence of ovarian cancer
that had presented a documented hypersensitivity reaction to the latest carboplatin infusion were treated
with LRDP.

Patients characteristics and type of infusion reaction are shown in Table 2. Cutaneous reaction was the
most frequent type of reaction to standard carboplatin administration in our series. All patients presented