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

• Published in: Daru 2017-04, Vol.25 (1), p.12-12, Article 12
• Main Authors: Visacri, Marília Berlofa, Pincinato, Eder de Carvalho, Ferrari, Graziele Baldan, Quintanilha, Júlia Coelho França, Mazzola, Priscila Gava, Lima, Carmen Silvia Passos, Moriel, Patricia
• Format: Article
• Language: English
• Subjects: Anemia; Anemia - chemically induced; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - urine; Biomedical and Life Sciences; Biomedicine; Cancer therapies; Chemoradiotherapy - methods; Chemotherapy; Cisplatin - adverse effects; Cisplatin - pharmacokinetics; Cisplatin - therapeutic use; Cisplatin - urine; Deoxyribonucleic acid; DNA; Drug dosages; Female; Head & neck cancer; Head and Neck Neoplasms - therapy; Hematology; Humans; Lymphopenia - chemically induced; Male; Medicinal Chemistry; Middle Aged; Mitochondrial DNA; Nausea; Nausea - chemically induced; Patients; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharyngeal Neoplasms - therapy; Prospective Studies; Radiation therapy; Research Article; Rodents; Studies; Urine
• ISSN: 2008-2231; 1560-8115; 2008-2231
• DOI: 10.1186/s40199-017-0178-9

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/m 2 ) 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