[Comparative Safety Study of Original and Generic Docetaxel without Alcohol in the Treatment of Breast Cancer].

Docetaxel(DTX)is a key drug for breast cancer treatment; however, its formulation contains alcohol, which can cause several problems. We have been preparing original DTX without using its accompanying alcohol-solubilizing solution since 2013 and switched to generic DTX without alcohol in 2015. In this study, we compared adverse events between the original and generic DTX, both of which did not contain alcohol. We retrospectively investigated the occurrence of adverse events in breast cancer patients who were treated with DTX(75 mg/m2)as neoadjuvant or adjuvant chemotherapy from January 2013 to December 2017. 201 patients participated in the study(75/126 in the original/generic groups). The incidence of febrile neutropenia, hypersensitivity reactions, and skin toxicities did not differ between the groups(p=0.620, 0.066, 0.205). The severity of edema and peripheral neuropathy was significantly worse in the patients receiving the generic DTX (p<0.01, <0.01). The findings suggest a difference in the incidence of edema and peripheral neuropathy following treatment with the original and generic DTX, regardless of the inclusion of alcohol.

Risk Factors Associated with Cisplatin-Induced Nephrotoxicity in Patients with Advanced Lung Cancer.

Cisplatin (CDDP) combination chemotherapy is widely administered to patients with advanced lung cancer. The dose depends on multiple factors, including whether the tumor is non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). Although efficacy is limited by cisplatin-induced nephrotoxicity (CIN), little is known about the risk factors for this complication. The aim of this study was to identify the risk factors for CIN in patients with advanced lung cancer, both NSCLC and SCLC. We retrospectively reviewed clinical data for 148 patients who underwent initial chemotherapy including CDDP ≥50 mg/m2 per patient per day for the first course at Kyushu Medical Center between October 2010 and September 2013. All data were collected from the electronic medical record system. Nephrotoxicity was defined as an increase in serum creatinine concentration of at least grade 2 during the first course of CDDP chemotherapy, as described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. CIN was observed in nine patients. Univariate analysis revealed that cardiac disease and lower baseline serum albumin (Alb) values conferred a higher risk of nephrotoxicity (p<0.05). The cut-off value of Alb was 3.8 g/dL, calculated by receiver operating characteristics (ROC) curves. Multivariable logistic regression analysis revealed that cardiac disease (odds ratio=11.7; p=0.002) and hypoalbuminemia (odds ratio=6.99 p=0.025 significantly correlated with nephrotoxicity. In conclusion, cardiac disease and low baseline Alb values are possible risk factors for CIN.

[Efficacy and safety of transdermal fentanyl patches for opioid initiation in patients with gastrointestinal obstruction].

The transdermal fentanyl patch (TDF) can be used when switching from other opioids; therefore, little is known about the efficacy and safety of TDF patches applied for opioid initiation. However, TDF patches have been applied for opioid initiation in gastrointestinal cancer patients with gastrointestinal obstruction. In this study, we retrospectively investigated 12 gastrointestinal cancer patients to evaluate the efficacy and frequency of adverse effects of TDF patches compared to oral oxycodone (OXY) for opioid initiation. The frequency of adverse effects such as nausea, somnolence, and constipation in the TDF patch group was 25%, 41.7%, and 8.3%, respectively. No severe adverse effects were observed, and there was no significant difference between the TDF patch and OXY groups. Moreover, according to the numerical pain rating scale(ranging from 0 [no pain] to 10 [worst possible pain]), the pain intensity in the TDF patch group decreased from 5.42 on the first day to 3.33 after 3 days (p=0.0377), and 2.67 after 7 days (p=0.0089), with no significant difference between groups. Our study results suggest that TDF patches applied for opioid initiation may be useful for gastrointestinal cancer patients with gastrointestinal obstruction.

Pharmacokinetics and elimination efficiency of linezolid during dialysis.

Linezolid (LZD) is an option for treating infections caused by multi-resistant Gram-positive bacteria. The protein-binding rate of LZD markedly influences its elimination by dialysis, with limited data suggesting that LZD is cleared by intermittent hemodialysis. Here, we investigated the protein-binding rate and elimination efficiency of LZD in a sepsis patient receiving dialysis. The oral administration of LZD at 600 mg/day resulted in protein-binding and free rates of the drug of 20.4% and 79.6%, respectively, 24 h after administration. By comparing the LZD concentration before and after dialysis, the elimination efficiency of free LZD as a result of dialysis was found to be 40.6%. Our sepsis patient showed higher plasma concentrations of LZD at trough after hemodialysis than the reported concentrations in normal renal function patients. However, it is not clear from our present findings if a relationship exists between myelosuppression and plasma LZD concentration.

[Risk factors for hyperammonemia during mFOLFOX6 treatment].

Patients undergoing mFOLFOX6 treatment were classified into a hyperammonemia group (NH3 group) or a non-hyperammonemia group (Non-NH3 group) in order to investigate risk factors related to the onset of hyperammonemia. The NH3 group demonstrated significantly lower lymphocyte counts, hemoglobin and albumin levels, and estimated glomerular filtration rates compared to the Non-NH3 group, suggesting that the NH3 group was experiencing renal dysfunction and loss of skeletal muscle mass due to malnutrition. Amino acid fractionation in the NH3 group revealed high urea levels, and delayed urea excretion was identified. Fluorocitric acid, a fluorouracil metabolite, inhibits aconitase in the tricarboxylic acid cycle. In addition, decreased renal urea transporter function due to renal impairment leads to delayed urea excretion. These factors may induce secondary decreases in urea cycle function, leading to hyperammonemia.

Correlation between serum linezolid concentration and the development of thrombocytopenia.

We evaluated the possible association between trough linezolid (LZD) concentrations and platelet counts using a dose-response curve with a logit model equation. We demonstrated that trough LZD concentrations correlated with platelet counts. A significant decrease in platelet count was observed in patients with trough LZD concentrations higher than 22.1 µg/ml.

Pharmacokinetics and administration method of gentamicin in a patient on haemodialysis.

We investigated the pharmacokinetics of gentamicin in a haemodialysis patient treated for endocarditis caused by methicillin-resistant Staphylococcus aureus and found that the administration of gentamicin immediately prior to dialysis was a suitable strategy for reaching target maximum drug concentration (Cmax) values and low trough levels.

[Factor analysis of outcomes during drug-resistant bacterial infection treatment].

Factors related to poor outcome in drug-resistant bacterial infection treatment were analyzed based on surveys at 54 National Hospital Organization facilities. Results showed common etiological causes of Methicillin-resistant Staphylococcus aureus (MRSA) and Penicillin-resistant Streptococcus pneumoniae (PRSP). Specifically, the odds ratio in the elderly, aged 75 years and older, was 1.473 (p=0.006) for MRSA and 6.401 (p=0.0001) for PRSP. Among those undergoing tracheal intubation, the odds ratio was 1.767 (p=0.021) for MRSA and 4.185 (p=0.0001) for PRSP, showing that advanced age and tracheal intubation tended to aggravate disease. MRSA-specific causes were pneumonia with an odds ratio of 2.426 (p=0.0001) and sepsis with one of 1.417 (p=0.013). Causes specific to Multi-drug resistant Pseudomonas aeruginosa (MDRP) were Intravenous hyperalimentation (IVH) with an odds ratio of 2.078 (p=0.0001) and urinary-tract infection with one of 0.566 (p=0.027). The individual roles of these factors in poor outcomes must thus be clarified to develop preventive measures against them.

[Protective effects of d-chlorpheniramine maleate pre-treatment against acute side effects of Irinotecan(CPT- 11)].

It is wellknown that cholinomimetic side effects, such as sedation, abdominal pain, nasal flow and watery eyes, may develop in patients in the early stage of Irinotecan (CPT-11) administration; however, there have been no investigations concerning methods for preventing the development of these side effects. To assess the protective effects of pre-treatment with d-CM on cholinomimetic side effects in the early stage after Irinotecan (CPT-11) administration, we prescribed d- Chlorpheniramine maleate (d-CM) to a group of patients prior to Irinotecan (CPT-11) administration. Twenty members from the group of non-d-CM-treated patients (n=39) and 4 members from the group of treated patients (n=20) complained of side effects. The pre-administration of d-CM significantly reduced the number of patients with side effects (p<0.05). The relative risk (RR) for the frequency of side effects was 0.39 (95% CI; 0.15-0.98), demonstrating that the frequency of side effects was significantly reduced. Based on theses findings, we concluded that the pre-administration of d-CM had protective effects against side effects that might develop in the early stage after Irinotecan (CPT-11) administration.

Pharmacokinetics of carboplatin in a hemodialysis patient with small-cell lung cancer.

PURPOSE: We examined a method to determine the dose of carboplatin and the timing of hemodialysis in carboplatin-based chemotherapy for a hemodialysis patient with cancer. METHODS: Carboplatin-based chemotherapy was performed for a patient with small-cell lung cancer who was receiving hemodialysis. The dose of carboplatin was calculated based on body surface area in the first cycle (480 mg/body, Day 1) and based on the Calvert formula with the aim of achieving AUC of 5 mg/ml min in the second cycle (170 mg/body, Day 1). Carboplatin was continuously infused for 1 h on Day 1 of each cycle. Hemodialysis was performed for 4 h beginning 1 h after administration of carboplatin. RESULTS: The AUC of free carboplatin administered in the first and second cycles was 13.45 and 5.74 mg/ml min, respectively, and t (1/2) was 24.66 and 21.84 h, respectively. Protein binding ratio depended on the time after administration and reached a value ≥50% only at ≥24 h administration. CONCLUSION: Based on the results of this study, a value close to the targeted AUC can be obtained in a hemodialysis patient with cancer when carboplatin is administered at a dose determined based on the Calvert formula. These results may be useful to achieve a targeted AUC in hemodialysis patients. A certain amount of carboplatin can be eliminated by performing hemodialysis in an early phase when protein binding ratio is low after transition to the elimination phase to enable stable the concentration.