[Efficacy of Tapentadol for Neuropathic Pain in Cancer].

Neuropathic pain in patients with cancer often do not respond to both opioid and non-opioid analgesics. Tapentadol has two medical effects: action on the µ opioid receptor and inhibition of noradrenaline reuptake; thus, it is expected to be effective for neuropathic pain. We investigated its effect on neuropathic pain in 40 patients with cancer who received tapentadol between June 2017 and May 2020 at the Japanese Red Cross Nagoya Daini Hospital. We compared the level of neuropathic pain using an NRS before and after tapentadol administration. The NRS score(median)decreased from 7 to 4.5 within 15 days after first administration or dose increase(p<0.05). Twenty-two patients(55%)showed more than 33% improvement in the NRS score. These results suggest that tapentadol may contribute to a reduction in neuropathic pain.

[Necessity of Serum Calcium Concentration Measurement for Investigating Hypocalcemia Induced by Denosumab].

Denosumab is widely used for treating bone metastases in patients with advanced cancer. However, hypocalcemia has been reported as a serious adverse effect during this treatment. Therefore, monitoring serum calcium concentration is essential. During long-term continuous administration ofdenosumab, the burden ofeach blood sampling occasion and medical economics should be clarified; however, the appropriate blood sampling frequency has not yet been confirmed. In the present study, we performed a retrospective investigation of serum calcium concentration after denosumab administration. The results indicated that serum calcium concentration tended to increase with repeated administration. A significant increase was observed at the time ofthe third and sixth administration. This suggested that it was possible to reduce the frequency ofblood sampling during long-term administration ofdenosumab with appropriate calcium supplementation.

[Safety Assessment of a Short Hydration Regimen for Outpatient Cisplatin-Based Chemotherapy].

BACKGROUND: During administration of thecisplatin (CDDP)containing regimen, hospitalization is necessary to ensure adequate hydration. However, short hydration is widely used when administering CDDP in outpatient chemotherapy centers. METHOD: To assess the safety of the administration of CDDP during short hydration, we retrospectively evaluated adverse events and complications in the outpatients who received CDDP during short hydration between April 2012 and December 2014 in our hospital. RESULT: Sixty patients received CDDP during short hydration. Eighteen patients with non-small cell lung cancer, 17 with gastric cancer, 10 with small cell lung cancer, 9 with cervical cancer, 4 with biliary tract cancer, 1 with endometrial cancer, and 1 with duodenal papilla cancer were retrospectively evaluated. Fifty-five patients completed CDDP treatment(including treatment until PD). The reasons for discontinuation of CDDP treatment were deterioration of general condition, ileus, pneumothorax, cholangitis, and rejection of oral rehydration. Hydronephrosis after CDDP treatment during short hydration(weekly CDDP regimen)was observed in 1 patient. No patient discontinued CDDP due to grade 3 or 4 adverse events. CONCLUSION: No discontinuation of CDDP associated with a short hydration regimen suggests that it has enabled thesafeadministration of CDDP to outpatients.

[Performance of a portable continuous infusion pump (SUREFUSER A) in continuous infusion of 5-FU].

Therapy with mFOLFOX6/FOLFIRI used in treating colorectal cancer is typical of the regimens performed in outpatient settings. In this therapy, 46-h continuous infusion of 5-fluorouracil (5-FU) with concomitant oxaliplatin and irinotecan hydrochloride is conducted. The portable continuous infusion pump that makes continuous infusion possible has a non-electric structure, so variation in the infusion rate is seen. There are known effects of 5-FU concentration and temperature, and many studies have reported on the precision. In our hospital, we have experienced many cases of incomplete infusion and delays for the above reasons. We changed the specifications of the infusion pump to correspond to the kinematic viscosity of 5-FU and made all drug solution amounts uniform. We measured the time required to administer the drug solution from the time the infusion was started (recorded by a nurse) and the time it was completed (recorded by the patient), and confirmed the precision of the pump after the changes were made. It was found that while there was a decrease in the infusion rate at which the effect of the kinematic viscosity of 5-FU is seen, the mean infusion time was kept to within 46+/-10% hours in more than 90% of patients. There were no effects from concentration differences in 5-FU, and the completion time was reduced. The management and lifestyles of individual patients are potential factors in precision errors, and it is important to explain in advance to patients the necessity of secure fixation and infusion pump problems that might occur.

Dose adjustment strategy for oral microemulsion formulation of cyclosporine: population pharmacokinetics-based analysis in kidney transplant patients.

The present study aims to determine the population pharmacokinetic parameters of cyclosporine (CsA) after multiple oral administration of the microemulsion formulation, Neoral, in kidney transplant patients and to propose a limited sampling strategy to predict AUC(0-4h) using them and the Bayesian method. The AUC(0-4h) is a parameter that has recently been recommended as an index for the dose adjustment in therapeutic drug monitoring of CsA. Blood samples were obtained at the trough level and at hourly intervals up to 5 hours from 125 patients (78 male and 47 female) who were receiving Neoral twice daily, and whole-blood concentrations of CsA were measured. The population pharmacokinetic parameters were estimated using the NONMEM computer program and a linear two-compartment model with first-order absorption. The observed AUC0-4h and concentrations at different sampling times were compared with those computer-predicted by the Bayesian method, using the population pharmacokinetic parameters and 2 or 3 concentrations from those at 0 h (C(0)), 1 h (C(1)), and 2 h (C(2)) after administration. Typical values for the absorption rate constant (k(a)), elimination rate constant (k(el)), apparent volume of distribution for the central compartment (Vd/F), and oral clearance (CL/F) calculated by population pharmacokinetic analysis were 2.16 hours(-1), 0.547 hours(-1), 43.3 L, and 23.7 L/h, respectively. The CsA concentrations predicted using either the 2-point or 3-point sampling strategy exhibited an excellent correlation with the observed values (R(2) > 0.81), and accordingly, the predicted AUC(0-4h) values were in excellent agreement with those observed. The best predictability of AUC(0-4h) was found for the 3-point sampling strategy using C(0), C(1), and C(2), closely followed by a 2-point sampling strategy using C(1) and C(2). The present findings suggest that a simplified strategy based on population pharmacokinetics can accurately predict AUC(0-4h) from concentrations at 2 or 3 sampling time points, providing an excellent method for the daily dose adjustment of Neoral in routine clinical use for kidney transplant patients.