A modified protocol for rapid desensitization to chemotherapy agents

Abstract

Desensitization protocols for chemotherapy agents (taxanes and platinum salts) have been extensively performed to safely administer these drugs to patients who have previously suffered a hypersensitivity reaction (HSR). Standardized protocols have been published using 12 or 16 steps to reach the cumulative dose in every patient. All these protocols were based on the preparation of 3 different solutions at 100-fold, 10-fold, and 1fold dilution of the final target concentration. However, from the pharmacological point of view, a reasonable doubt on the stability of diluted concentrations arises because there are no published data available. For example, concentrations higher than 0.2 and 0.1 mg/mL are known to be stable for paclitaxel and carboplatin, respectively, but no studies have been performed with lower concentrations. Docetaxel is the least stable drug. According to the Food and Drug Administration, a sodium chloride solution or 5% dextrose solution to produce a final docetaxel concentration of 0.3 to 0.74 mg/mL is stable for 4 hours under ambient room temperature and lighting conditions but there are no data for longer periods of time or lower concentrations. To address this potential problem of stability, a new protocol of desensitization with carboplatin and taxanes was developed. We present a proposed protocol that perfectly fits with the recommended published dosages for these chemotherapy agents but using the same solution during the whole procedure. Twelve patients with HSR to taxanes or platinum salts and for whom continued treatment with these drugs was considered advantageous were evaluated between July 2013 and April 2016. All patients were women with a median age of 50 years (range, 35-72 years) and had received antineoplastic treatment due to either ovarian and/or breast cancer. Eight of them had suffered at least 1 reaction with carboplatin and the remaining 4 with taxanes (2, paclitaxel and 2, docetaxel). Nine patients presented severe reactions involving the respiratory and/or the cardiovascular system. Most patients (11 of 12) presented with cutaneous symptoms (pruritus, flushing, or urticaria). During this period we have used different brands according to the availability at the hospital: docetaxel (Taxotere, Sanofi Aventis, Essex, United Kingdom; Docetaxel, Accord, Middlesex, United Kingdom; Docetaxel, Actavis, Devon, United Kingdom), carboplatin (Carboplatin, Pharmacia Nostrum, Madrid, Spain; Carboplatin, Accord, Middlesex, United Kingdom; Carboplatin, Kabi, Hampshire, United Kingdom), and paclitaxel (Taxol, Bristol Myers Squibb, Latina, Italy; Paclitaxel, Hospira, Madrid, Spain).