Concomitant usage of lapatinib, a cytochrome P450 (CYP) 3A4 substrate and dexamethasone, a CYP3A4 inducer, is a pharmacokinetic drug-drug interaction. This combination may increase the formation of reactive lapatinib metabolites, which is potentially hepatotoxic. This study aims to evaluate the clinical effect of dexamethasone on incidence of hepatotoxicity and to ascertain its in vitro role using a parallel cell culture model experimental setup. Clinical effects of dexamethasone on lapatinib-induced hepatotoxicity were evaluated in a nested case-control study based on 120 patient data obtained from our records. For the in vitro experiment, metabolically competent transforming growth factor α mouse hepatocytes (TAMH) were treated with lapatinib and viabilities were compared in the presence or absence of dexamethasone. After adjusting for confounders, patients receiving the combination were 4.57 times (95% CI 1.23-16.88, p = 0.02) more likely to develop hepatotoxicity and 3.48 times (95% CI 1.24-9.80, p = 0.02) more likely to develop a clinically important change in alanine aminotransferase than compared to the other group. Treatment of TAMH cells with lapatinib and dexamethasone caused a further reduction in viability, as compared to treatment with lapatinib alone. At 5 μM lapatinib, the introduction of dexamethasone 20 μM produced a 59% decline in viability. This is the first study to document a clinically important interaction between lapatinib and dexamethasone, which associates with an increased occurrence of hepatotoxicity. The in vitro findings have provided substantiating evidence and insights on the role of dexamethasone in lapatinib-induced hepatotoxicity.

The use of olanzapine as part of standard antiemetic regimen is cost-effective for the prevention of CINV in patients receiving HEC in multiple SEA countries.

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

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Objective: To investigate the prevalence of chemotherapy-induced adverse events and the associated risk factors in pediatric patients with osteosarcoma. Methods: This retrospective cross-sectional study enrolled 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) treated at