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

Abstract

BackgroundCisplatin 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.MethodsOutpatients 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.ResultsIn 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.ConclusionsThe 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

GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms in outcomes of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

“…Therefore, the effects of RT are potentiated by CDDP 4 . Although the beneficial effects of CDDP are unequivocal, it is associated with numerous side effects involving the hematologic, gastrointestinal, renal, and auditory systems in HNSCC 5,6 . HNSCC patients treated with CDDP may also experience resistance and/or tumour recurrence within five years of follow-up 7 .…”

Association of Urine Platinum With Acute Kidney Injury in Children Treated With Cisplatin for Cancer

“…Erdlenbruch et al 24 demonstrated a correlation between peak urine platinum and the nadir of GFR in 12 children treated with cisplatin. A more recent study by Visacri et al 26 found no association between urine platinum and kidney function after cisplatin infusion. The contradicting results from these studies preclude the ability to draw conclusions regarding the relationship between urine platinum and cisplatin‐associated nephrotoxicity.…”

MiR-3168, miR-6125, and miR-4718 as Potential Predictors of Cisplatin-Induced Nephrotoxicity in Patients with Head and Neck Cancer

“…Despite the proven e cacy of cisplatin treatment, patients frequently experience toxicity that limits the duration and e cacy of therapy. Nephrotoxicity is one of the most frequent and dose-limiting cisplatininduced toxicities, with a prevalence that varies between 30% and 50% in patients treated with ≥80 mg/m 2 cisplatin [3,4].…”