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

• Grant number: 17/06928-6
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: May 01, 2017
• End date: October 31, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Patricia Moriel
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/18294-3 - Evaluation of the use of N-acetylcysteine attenuating cisplatin-induced toxicities by oxidative stress in head and neck cancer patients, AP.R

Abstract

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 ofcisplatin excretion in the urine of patients undergoing high-dose cisplatin chemotherapyand radiotherapy for head and neck cancer. Outpatients with head and neck cancer received a first cycle of high-dosecisplatin 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 wasevaluated 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 andregression analysis were performed to assess the relationship between ADRs andcisplatin excretion in the urine. In total, 59 patients with a mean age of 55.6 ± 9.4 years were analysed; mostpatients were male (86.4%), white (79.7%), and with pharyngeal tumours in advancedstages (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 meancisplatin excretion was 70.3 ± 64.4, 7.3 ± 6.3, and 5 ± 4 ¼g/mg creatinine at 0-12, 12-24, and 24-48 h, respectively. Statistical analysis showed that the amount of cisplatinexcreted did not influence the severity of ADRs. The most frequent ADRs were anaemia, lymphopenia, and nausea.Grades 1 and 2 were the severities for most ADRs. The period over which the highestcisplatin excretion observed was 0-12 h after chemotherapy, and cisplatin excretioncould not predict toxicity. (AU)