Adverse drug reactions and kinetics of cisplatin excretion in urine of patients undergoing cisplatin chemotherapy and radiotherapy for head and neck cancer: A prospective study

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DARU, Journal of Pharmaceutical Sciences
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Visacri M.B.
Pincinato E.D.C.
Ferrari G.B.
Quintanilha J.C.F.
Mazzola P.G.
Lima C.S.P.
Moriel P.
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© 2017 The Author(s).Background: Cisplatin is a high-potency anticancer agent; however, it causes significant adverse drug reactions (ADRs). Potential pharmacokinetic markers must be studied to predict or prevent cisplatin-induced ADRs and achieve better prognosis. This study was designed to investigate the relationship between ADRs and kinetics of cisplatin excretion in the urine of patients undergoing high-dose cisplatin chemotherapy and radiotherapy for head and neck cancer. Methods: Outpatients with head and neck cancer received a first cycle of high-dose cisplatin chemotherapy (80-100 mg/m2) concurrent to radiotherapy. ADRs (haematological, renal, and gastrointestinal reactions) were classified based on severity by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4, grade 0-4). The kinetics of cisplatin excretion in urine was evaluated by high-performance liquid chromatography over three time periods: 0-12, 12-24, and 24-48 h after the administration of cisplatin. Spearman Correlation test and regression analysis were performed to assess the relationship between ADRs and cisplatin excretion in the urine. Results: In total, 59 patients with a mean age of 55.6 ± 9.4 years were analysed; most patients were male (86.4%), white (79.7%), and with pharyngeal tumours in advanced stages (66.1%). The most frequently observed ADRs were anaemia (81.4%), lymphopenia (78%), and nausea (64.4%); mostly grades 1 and 2 of toxicity. The mean cisplatin excretion was 70.3 ± 64.4, 7.3 ± 6.3, and 5 ± 4 μg/mg creatinine at 0-12, 12-24, and 24-48 h, respectively. Statistical analysis showed that the amount of cisplatin excreted did not influence the severity of ADRs. Conclusions: The most frequent ADRs were anaemia, lymphopenia, and nausea. Grades 1 and 2 were the severities for most ADRs. The period over which the highest cisplatin excretion observed was 0-12 h after chemotherapy, and cisplatin excretion could not predict toxicity. Graphical abstract:
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Anemia , Antineoplastic Agents , Chemoradiotherapy , Cisplatin , Female , Head and Neck Neoplasms , Humans , Lymphopenia , Male , Middle Aged , Nausea , Pharyngeal Neoplasms , Prospective Studies
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