Predictors of Chemotherapy Induced Adverse Events in Pediatric Osteosarcoma Patients.

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 Srinagarind Medical Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, between January 1, 2008 and December 31, 2018. The prevalence of major adverse events and a correlation between baseline characteristics and adverse events were analyzed using a generalized estimating equation model. RESULT: The prevalence of adverse events in 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) was determined as chemotherapy-induced nausea and vomiting (29.2%; n=296), hepatotoxicity (21.2%; n=215), anemia (70.69%; n=719), neutropenia (26.65%; n=271), and thrombocytopenia (13.65%; n=139). Factors associated with chemotherapy-induced hepatotoxicity included methotrexate dose ≥ 12 g/m2 (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.22-1.39; P<0.001), plasma concentration of methotrexate at 72 hours >0.1 µM (OR 1.22; 95% CI 1.19-1.25; P<0.001), and pre-hydration rate ≤ 125 mL/m2/h (OR 1.10; 95% CI 1.07-1.12; P<0.001). CONCLUSION: Major adverse events are becoming more common in pediatric osteosarcoma patients, and risk factors include larger chemotherapy doses, higher plasma methotrexate concentrations, and a slower pre-hydration rate. The outcomes of the study could aid in the better treatment of toxicity in children with osteosarcoma.

An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study.

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.

Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for managing highly emetogenic chemotherapy in Southeast Asia: a multinational study.

PURPOSE: Recent studies suggested that olanzapine, together with dexamethasone and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA) countries where resources are limited. We aimed to evaluate the cost-effectiveness of incorporating olanzapine into standard antiemetic regimens for the prevention of CINV in patients receiving HEC among SEA countries. METHODS: Using a decision tree model, clinical and economic outcomes associated with olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA + aprepitant) for CINV prevention following HEC were evaluated. This analysis was performed in Thailand, Malaysia, Indonesia, and Singapore, using societal perspective method with 5-day time horizon. Input parameters were derived from literature, network meta-analysis, government documents, and hospital databases. Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted life year (QALY) gained. A series of sensitivity analyses including probabilistic sensitivity analysis were also performed. RESULTS: Compared to doublet antiemetic regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026 with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and Indonesia, respectively. Compared to triplet antiemetic regimen, switching aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD 60.91 in Singapore. The probability of being cost-effective at a cost-effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across countries. CONCLUSION: 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.

Effectiveness of olanzapine for the treatment of breakthrough chemotherapy induced nausea and vomiting.

OBJECTIVE: To evaluate safety and efficacy of olanzapine for breakthrough emesis in addition to standard antiemetic regimen in cancer patients receiving highly emetogenic chemotherapy. MATERIAL AND METHOD: A phase II prospective open label clinical trial was conducted in tertiary care based hospital. Forty-six cancer patients diagnosed with solid tumors were enrolled to receive at least one cycle of highly emetogenic chemotherapy (HEC) every two to four weeks. Each patient was provided standard antiemetic consisting of the generic form of ondansetron plus corticosteroids and metoclopramide according to clinical practice guideline. Olanzapine was administered as 5 mg orally every 12 hours for two doses in patients experiencing breakthrough emesis for at least one episode despite standard prevention. The efficacy and tolerability were evaluated every six hours for 24 hours (utilizing Index of Nausea, Vomiting and Retching: INVR tool). RESULTS: Of 46 evaluable patients receiving HEC and additional olanzapine between September 2009 and July 2010, the complete response of breakthrough emesis, retching, and nausea control among patients were 60.9%, 71.7%, and 50.0%, respectively. Adverse events reported were mild and tolerable including dizziness, fatigue, and dyspepsia. CONCLUSION: Olanzapine is considered to be safe and effective treatment of breakthrough vomiting in cancer patients undergoing highly emetogenic chemotherapy in the present study.

Effect of CYP3A4 inducer dexamethasone on hepatotoxicity of lapatinib: clinical and in vitro evidence.

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.

Validity and reliability of the Thai Mini Asthma Quality of Life Questionnaire.

OBJECTIVE: The present study assessed the validity and reliability of the Thai Mini AQLQ in the Easy Asthma Clinic, Srinagarind Hospital. MATERIAL AND METHOD: The present study used a cross sectional design, using an interview method by two trained-interviewers. The Thai Mini AQLQ consists of 15 items categorized into Symptoms, Activities, Emotions, Environment and Overall Scores. Scores range from 0 to 7 with higher scores meaning better quality of life. Cronbach's alpha was used to test for internal consistency reliability. Known group validation regarding asthma control was analyzed by the t-test and multiple regression, adjusting for age, gender and education. RESULTS: Of 168 patients recruited, 113 were controlled and, of these 55 were uncontrolled asthma patients, with an average age 53 +/- 13 years. Patients with controlled asthma reported significantly better scores in all domains compared with uncontrolled asthma: symptoms 6.6 +/- 0.54 vs. 4.7 +/- 1.14, p < 0.001; Activity 6.7 +/- 0.57 vs. 5.0 +/- 1.36, p < 0.001; emotion 6.4 +/- 0.91 vs. 4.6 +/- 1.67, p < 0.001; environment 5.3 +/- 1.10 vs. 4.1 +/- 1.24, p < 0.001 and overall scores 6.3 +/- 0.51 vs. 4.6 +/- 0.96, p < 0.001. Adjusting for age, gender and education using multiple regression, there was also a significant difference in all domains of Thai Mini AQLQ between the controlled and uncontrolled asthma patients. Internal consistency reliability was within the acceptable range (> 0.7) for all domains, except environment (overall 0.910; symptoms 0.855; activities 0.886; emotions 0.765 and environment 0.616). CONCLUSIONS: Thai Mini AQLQ has known to be reliable and valid. Further study on test-retest reliability and responsiveness to change are warranted.