[A Survey on the Concomitant Use of Drugs with Enzalutamide in Medical Practice-The Effects and Resultant Decrease in Efficacy].

PURPOSE: Enzalutamide is a potent inducer of cytochrome P450 substrates. Hence, it induces major metabolizing enzyme effects in some of the concomitant drugs, raising the possibility of decreased efficacy. We investigated the actual status of drugs for which precautions for co-administration are indicated during concomitant use with enzalutamide. METHODS: We retrospectively investigated the duration of enzalutamide use, concomitant medications, laboratory values, and events using the medical records of patients prescribed enzalutamide for castration-resistant prostate cancer at the National Cancer Center Hospital from May 2014 to May 2017. RESULTS: The median age of the 107 studied patients was 74 years[range: 53-93], median duration of enzalutamide prescriptions was 120 days[range: 14-1,008], and the median number of concomitant medications(components)was 6[range: 0-16]. Sixty nine patients(64%)were taking drugs that could be affected by enzyme induction. The medications listed in the concomitant use section of the package insert were warfarin(3 patients) and omeprazole(2 patients). In this study, 4 patients(except for 1 on warfarin)were taking other drugs that could be affected by enzyme induction. Events considered to possibly reduce their efficacy during concomitant use with enzalutamide were elevated blood pressure and blood clots. CONCLUSIONS: When enzalutamide is used in combination with other drugs, there exists the possibility that the effect of concomitant medications may be weakened by enzyme induction.

Association between Cerebral Infarction Risk and Medication Adherence in Atrial Fibrillation Patients Taking Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) are available for nonvalvular atrial fibrillation patients. The advantage of DOACs is that regular anticoagulation monitoring is not required. However, adherence to the recommended regimen is essential. We investigated the association between medication adherence and the risk of cerebral infarction in patients taking DOACs. Patients admitted to any of the participating hospitals for cerebral infarction from September 2018 to February 2020 and prescribed DOACs before admission were defined as the case group, and patients hospitalized for diseases other than cerebral infarction, except for bleeding disorders, and prescribed DOACs before admission were defined as the control group. A nested case-control study was adapted, and 58 and 232 patients were included in the case and control groups, respectively. Medication adherence was assessed by the pharmacists through standardized interviewing. The adjusted odds ratio for the risk of cerebral infarction for low-adherence patients (<80% adherence rate) against good-adherence patients (100% adherence rate) was 9.69 (95% confidence interval, 3.86-24.3; p < 0.001). The patients' age and other background characteristics were not found to be risk factors for cerebral infarction. In conclusion, low adherence is a risk factor for cerebral infarction in patients taking DOACs. Pharmacists should focus on maintaining ≥80% adherence to DOAC therapy to prevent cerebral infarction.

Accuracy of predicting the vancomycin concentration in Japanese cancer patients by the Sawchuk-Zaske method or Bayesian method.

BACKGROUND: In cancer patients treated with vancomycin, therapeutic drug monitoring is currently performed by the Bayesian method that involves estimating individual pharmacokinetics from population pharmacokinetic parameters and trough concentrations rather than the Sawchuk-Zaske method using peak and trough concentrations. Although the presence of malignancy influences the pharmacokinetic parameters of vancomycin, it is unclear whether cancer patients were included in the Japanese patient populations employed to estimate population pharmacokinetic parameters for this drug. The difference of predictive accuracy between the Sawchuk-Zaske and Bayesian methods in Japanese cancer patients is not completely understood. OBJECTIVE: To retrospectively compare the accuracy of predicting vancomycin concentrations between the Sawchuk-Zaske method and the Bayesian method in Japanese cancer patients. METHODS: Using data from 48 patients with various malignancies, the predictive accuracy (bias) and precision of the two methods were assessed by calculating the mean prediction error, the mean absolute prediction error, and the root mean squared prediction error. RESULTS: Prediction of the trough and peak vancomycin concentrations by the Sawchuk-Zaske method and the peak concentration by the Bayesian method showed a bias toward low values according to the mean prediction error. However, there were no significant differences between the two methods with regard to the changes of the mean prediction error, mean absolute prediction error, and root mean squared prediction error. CONCLUSION: The Sawchuk-Zaske method and Bayesian method showed similar accuracy for predicting vancomycin concentrations in Japanese cancer patients.

Comparison of valproate and levetiracetam for the prevention of busulfan-induced seizures in hematopoietic stem cell transplantation.

Anticonvulsant administration is the standard of care for prevention of busulfan-induced seizures (BIS) in hematopoietic stem cell transplantation (HSCT). While valproate interacts with other drugs, including carbapenem antibiotics, levetiracetam has no known clinically significant interactions. Only a few reports have discussed the use of levetiracetam for the prevention of BIS in HSCT recipients. This retrospective study aimed to evaluate the efficacy and safety of valproate and levetiracetam for BIS prophylaxis in adult HSCT recipients. We identified patients who received valproate or levetiracetam to prevent BIS at the National Cancer Center Hospital from December 2015 to November 2017. Ninety-one patients were analyzed (valproate group 45; levetiracetam group 46). No BIS occurred in either group. The pattern of anticonvulsant-related adverse events was similar in both groups, except for a higher incidence of rash in the valproate group. Carbapenem antibiotics were more frequently used in the levetiracetam group than in the valproate group. In conclusion, valproate and levetiracetam are effective and safe for the prophylaxis of BIS. Levetiracetam may be more useful in patients colonized with extended-spectrum beta-lactamase-producing bacteria due to its lack of any clinically significant drug-drug interactions.

Tolerability and Efficacy of Neoadjuvant Chemotherapy with a Tri-Weekly Interval Methotrexate, Doxorubicin, Vinblastine, and Cisplatin Regimen for Patients with Locally Advanced Bladder Cancer.

OBJECTIVE: Compared with standard treatment, a modified tri-weekly MVAC (methotrexate, doxorubicin, vinblastine, and cisplatin) treatment regimen with a high cisplatin dose intensity shows good efficacy and lower toxicity. Thus, we retrospectively investigated the tolerability and efficacy of a modified tri-weekly MVAC neoadjuvant regimen. METHODS: We analyzed 25 patients with locally advanced bladder cancer medicated by a modified tri-weekly MVAC neoadjuvant regimen that omits treatment on days 15 and 22. The efficacy and tolerability were assessed retrospectively. RESULTS: The numbers of patients in clinical stages 2, 3, and 4 were 13 (52.0%), 1 (4.0%), and 11 (44.0%), respectively. Surgery could be performed on all patients. Five patients (20.0%) had no cancer remaining in their surgical specimens. Remaining non-muscle-invasive cancer without metastasis was observed in 7 patients (28.0%), and the total downstaging rate was 44.0%. The 5-year overall and relapse-free survival rates were 79.0 and 75.0%, respectively. The overall relative dose intensity was 0.90. Serious hematologic toxicities rated grade 3 or greater were leukopenia in 6 patients (24.0%) and anemia in 1 patient (4.0%). CONCLUSIONS: Sufficient efficacy and tolerability of a modified tri-weekly MVAC neoadjuvant regimen were suggested. Thus, tri-weekly modified MVAC may be an option for neoadjuvant chemotherapy of advanced bladder cancer.

[Survey on oncologists-provided information on treatment-related infertility to breast cancer patients].

PURPOSE: Treatment-related infertility is an important issue facing breast cancer survivors of childbearing age. A previous study at the National Cancer Center Hospital between 2000 and 2004 analyzed 136 postoperative breast cancer patients under 40 years old, and found that only 7% of them had been provided with information on fertility-related issues by their treating physicians. However, the way in which information is shared may have changed, given the recent publication of national and international guidelines on fertility issues in cancer patients, and we hypothesized that there will be an increase in the percentage of cases in which information about fertility-related issues is provided. METHODS: We retrospectively analyzed patients 40 years old or younger who underwent surgery for primary breast cancer in this hospital between 2007 and 2009. We assessed patients' and oncologists' backgrounds, pathological stage, treatment plans, and whether or not oncologists provided explanations regarding fertility-related issues. RESULTS: One hundred cases were analyzed. Five percent, 15%, and 80%of patients were < 30, 30-35, and $gt;35 years old, respectively. Sixty-one percent of patients had partners, while 29%had prior deliveries. Information on fertility-related issues was provided to 56% of patients. Significant factors influencing whether information was provided were patients' reproductive history (odds ratio(OR): 5. 717, 95% confidence interval(CI): 1.752- 18.66, p=0. 004) and recommended treatment(OR: 24.22, CI: 3.150-186. 2, p=0. 017). By contrast, oncologists' background( specialty, gender, and duration of career as a physician)was not significant. The frequency with which treatment plans were changed did not correlate statistically with the provision of information on fertility-related issues. CONCLUSIONS: Information on treatment-related infertility is now provided much more frequently than in the past. We should encourage both patients and medical professionals to increase their awareness about this important issue.