[Examination of Actual Medical Material Cost and Cost Reduction Related to Exposure Prevention in the Preparation of Anticancer Drugs].

At Ogaki Municipal Hospital, we expanded the preparation of anticancer drugs using a closed system drug transfer device (CSTD)when revising medical fees in 2016. In this study, we investigated the number of regimens and number of preparations for outpatients in December 2017. Subsequently, the cost of all consumables related to the preparation of anticancer drugs was calculated. In total, 574 preparations of 68 regimens were conducted, with CSTD used in the preparation of 331 (57.7%)drugs. The cost associated with preparation of anticancer drugs was 1,608,163 yen/month, of which the CSTD cost was 1,135,315 yen/month(70.6%). Given the disproportionately high cost related to CSTD, we investigated for material cost reduction. Although CSTD has a mechanism for adjusting the differential pressure inside and outside the vial, the conditions were used to calculate medical fee; however, if we use what we do not have, we estimated that the facility burden would be reduced by 24.7%. CSTD can contribute not only to safety through exposure prevention but also to medical cost reduction through introduction of "Drug Vial Optimization." We believe it will continue to act as a medical evidence to reduce medical fee remuneration and ease the conditions of fee calculation.

[Treatment Continuation and Safety of Eribulin for the Treatment of Metastatic Breast Cancer].

The purpose of treatment for patients with metastatic breast cancer is to maintain the patient's quality of life(QOL)with continued treatment for as long as possible.Eribulin was approved in April 2011 for the treatment of metastatic breast cancer, further increasing the selection of therapies available for the management of this disease.The current study presents a retrospective review of 31 patients who received eribulin in our hospital, and analyzes the factors related to the continuation and safety of its use.The median treatment continuation was 114 days(range, 8-281 days), and the treatment involved an average of 5 courses(range, 1-13 courses).There were no significant differences in the continuation of eribulin with regard to the number of previous chemotherapy regimens and modifications undergone by the patients.Neutropenia accounted for 80.6% of adverse eventsBGrade 3; however, the recovery was rapid.The rates of peripheral neuropathy and liver function failures were 12.9% and 6.5%, respectively. These results suggest that eribulin can be continued to be administered with the aim of maintaining QOL, and the therapy can be adjusted according to the patient's situation and the occurrence of adverse events by reducing the dose and treatment delays.

[Economic Loss of Remaining Contents in Molecular Target Drug Preparation and the Simulation for Cost Saving].

While preparing an anticancer drug, even if it is an expensive molecular target drug, the remainder is not divided and saved for use in other patients; instead, it is discarded, resulting in waste of medical resources. In this study, we examined the economic loss in terms of medical costs by calculating the discarded amounts of 12 commonly used molecular target drugs at Ogaki Municipal Hospital, Japan between January 2012 and December 2014. We found, on average, that drugs valued at ¥ 52,593,182 were discarded annually. In particular, the discarded amounts of relatively expensive drugs, such as bevacizumab, bortezomib, and rituximab, were valued at ¥ 16,646,300, ¥ 15,866,289, and ¥ 8,401,324, respectively. Among these, the average amount of waste per administration of bortezomib was particularly expensive, at a cost of ¥ 67,325. Bortezomib is a commonly used treatment, resulting in excessive cumulative discarded cost. In an effort to save cost, we should consider using small capacity standard injections. Development of a simulation that used the remaining drug contents from only 1 day showed that bevacizumab alone accounts for an average cost saving of ¥1 2,542,191(75.3%) per year. This study suggests that effectively utilizing the remaining drug contents would ensure efficient use of medical resources, thereby reducing economic losses.

[Continuation of chemotherapy with bevacizumab for advanced and recurrent colorectal cancer].

We evaluated the association between the number of treatment courses with the concomitant use of bevacizumab(BV) and the reasons for discontinuation of the regimen in patients who received FOLFOX with or without BV as first-line chemotherapy and FOLFIRI with or without BV as second-line chemotherapy for advanced and recurrent colorectal cancer. In first-line treatment, 12 (2-46) and 10 (2-60) treatment courses were administered with and without BV, respectively, and this difference was not significant (p=0.60). In second-line treatment after first-line treatment with the concomitant use of BV, 11 (1-23) and 3 (1-12) treatment courses were administered with and without BV, respectively, and this difference was significant (p<0.01). Discontinuation due to adverse reactions was more frequent for first-line treatment (34.9%) than for second-line treatment (6.2%; p<0.01). The reasons for discontinuation due to adverse reactions during first-line treatment with BV were often associated with BV, and those during first-line treatment without BV were most often associated with peripheral neuropathy. Therefore, we conclude that early detection and prevention of adverse reactions are important in first-line treatment and that pharmacists as well should be involved in the monitoring and management of adverse reactions, although continued administration of BV even during second-line treatment after first-line treatment with BV is recommended.

[Induction of allergic reactions by anticancer drugs in outpatient chemotherapy].

We must understand the conditions during the onset of allergic reactions induced by anticancer drugs in order to respond with an appropriate treatment. We have therefore conducted this study, focusing on allergic reactions induced by each anticancer drug used in outpatient chemotherapy. Allergic reactions occurred in a total of 3.9% (76 cases), most of which were induced by platinum and taxane anticancer drugs. The number of administrations at symptom onset and the times of onset for platinums and taxanes were 11. 7±1. 3 times and 43. 3±4. 8 minutes for platinum; and 2. 3±0. 5 times and 18. 1± 3. 6 minutes for taxanes, respectively. This demonstrated a significant difference between these two drugs(both were p< 0. 01). In terms of re-administration following the onset of allergic reactions, 21 cases(72. 4%)out of 29 cases(38. 2%) were able to continue the administration of suspected drugs. We studied various factors surrounding the possibility of continued administration to two groups which were or were not able to continue receiving treatment. No significant differences were observed between the groups. For continuous safe treatment, it is necessary to understand the characteristics of allergic reactions induced by each anticancer drug. It is also advisable to consider possible precautions(by introducing prevention regimens)and appropriate measures at the time of re-administration, following the onset of allergic reactions.

[Tolerable evaluation for chemotherapy with S-1 plus cisplatin in elderly patients with advanced and recurrent gastric cancer].

This retrospective study examined the extent to which S-1 plus cisplatin is applicable to the elderly as a primary therapy for advanced or recurrent gastric cancer. Subjects under age 70 were categorized as the L group(n=42), and those age 70 and over were categorized as the O group(n=18). The 2 groups were compared in terms of their creatinine clearance(Ccr), performance status(PS), dose intensity(DI), reasons for regimen modification or discontinuation, and adverse reactions. The DI of S-1 was 100(50-100)% in the L group and 83(67-100)% in the H group(p<0. 0001), and the DI of cisplatin was 100(70-100)% in the L group and 87(75-100)% in the H group(p<0. 0001). The incidence of adverse reactions was similar for both groups. However, the S-1 plus cisplatin regimen was discontinued either at the patient's request, or based on the physician's determination that there were adverse reactions such as fatigue or anorexia. There were significantly more of these reactions in the H group(72. 2%)in comparison to the L group(42. 9%)(p=0. 0369). The elderly often had complications, and a decrease in PS as a result of repeatedly undergoing chemotherapy was noted(p=0. 0185). In conclusion, the elderly may have a low tolerance to S-1 plus cisplatin. When administering cancer chemotherapy to the elderly aged 70 and older, the patient's renal function, PS and Ccr, should be studied, and a regimen and dosage should be carefully selected.

[Appearance of skin and nail toxicity in patients with breast cancer who underwent trastuzumab-containing chemotherapy].

Trastuzumab is used for patients with metastatic breast cancer of HER2 over expression and adjuvant chemotherapy. Trastuzumab is recognized as a medicine with few adverse effects, although infusion reaction at its first dosage appears in high frequency as a main adverse effect. However, because we realized that there were many patients who appeared to have skin toxicity or nail toxicity, the adverse effects of trastuzumab were investigated retrospectively. Of 51 cases who underwent trastuzumab-containing chemotherapy, 25 cases(49. 0%)had skin toxicity, 14 cases(27. 5%) had nail toxicity, and 12 cases(23. 5%)had both toxicities. Skin toxicity and nail toxicity appeared in 14 of 25 cases(56. 0%) and 6 of 14 cases(42. 9%)respectively, within 6 months after the first medication dosage. Symptoms of skin toxicity were eruptions on the face and body(14 cases; 27. 5%), skin detachment or thinning on hands and feet(9 cases; 17. 6%), itching (8 cases; 15. 7%), skin drying(7 cases; 13. 7%)and so on. On the other hand, symptoms of nail toxicity were softening, thinning, or loss(13 cases; 25. 5%), paronychia(4 cases; 7. 8%), and discoloration(2 cases; 3. 9%). Our present findings suggest that skin toxicity and nail toxicity are highly frequent adverse events for those taking trastuzumab, although the drug is considered to be a molecular target drug with few adverse effects.

[The frequency and risk factor of herpes zoster infection in non-Hodgkin's lymphoma patients].

The chemotherapy treatment of non-Hodgkin's lymphoma(NHL)is associated with an increased risk of infection because of the intensity of the treatment. We examined the frequency of herpes zoster infections in 170 non-Hodgkin's lymphoma patients who had completed a chemotherapy course. Furthermore, we examined the risk factors contributing to these infections. This study took place in the Department of Hematology at Ogaki Municipal Hospital. Of the 170 patients treated in our facility, 25 developed herpes zoster(14. 7%), 19 of whom developed symptoms within 30 days of starting the chemotherapy treatment. Significant risk factors for the development of herpes zoster were post-autologous peripheral blood stem cell transplantation, relapsing patients, ten or more total treatments and the use of two or more regimens. In these cases the average interval of the treatments had to be extended from 6. 6 days to 14. 2 days due to the infection(comparing post - infection to pre-infection). We recommend the prophylactic use of low-dose acyclovir in patients with a higher risk of herpes zoster infection. We also recommend further monitoring of other opportunistic infections associated with chemotherapy usage.

[Continuous administration and safety of S-1 in adjuvant chemotherapy for gastric cancer].

Patients taking more than 8 courses of S-1 were classified in the continuous group (n=30) and those in whom S-1 was discontinued or reduced due to adverse reactions in the discontinuation/reduction group (n=29). Factors affecting the continuous administration of S-1 as the adjuvant chemotherapy were examined in the two groups. 10 cases in the continuous group and 8 cases in the discontinuation/reduction group began with a stage 1 reduction of the S-1 regimen. Significant factors which affected the reduction or discontinuation of S-1 due to adverse reactions were 1) serum albumin value (Alb) (odds ratio 9.227; 95% confidence interval 1.056-80.603, p=0.0196) and 2) creatinine clearance value (Ccr) (odds ratio 5.850; 95% confidence interval 1. 222-27.995, p=0.0221). Among the reasons for reduction or discontinuation, non-hematotoxicities including malaise, nausea and diarrhea accounted for 24/59 cases (40.7%) and hematotoxicities such as leukopenia for 5/59 cases (8.5%). The present study revealed that most of the reduction or discontinuation of S-1 was due to non-hematotoxicity such as malaise and suggested that these risks increased when Alb decreased to less than 3.5 g/dL and Ccr to less than 80 mL/min. Prognosis is reportedly satisfactory when administration of S-1 is continued for one year even if withdrawal or reduction is necessary during the period. Serious adverse reactions will have ill effects on future compliance with to administration in patients who have experienced them. The above results indicate that the occurrence of non-hematotoxicity should be observed carefully in patients with Alb less than 3.5 g/dL and Ccr less than 80 mL/min at the beginning of S-1 administration, and these patients should receive appropriate guidance. Modification or reduction of S-1 regimen at the beginning may be one way to alleviate hematotoxicity.

[Comparative safety evaluation of first- and second-line therapy with carboplatin + paclitaxel for advanced non-small cell lung cancer].

The study was carried out to compare the incidence of hematological toxicity between 14 cases with CDDP+VNR as first line therapy followed by CBDCA+PTX as second-line therapy, and 21 cases with CBDCA+PTX as first-line therapy for nonsmall cell lung cancer. The incidences of thrombocytopenia were 78. 6% in the second-line and 42. 9% in the first-line with a significant difference (p=0. 0364). The incidences of neutropenia at grade 3 or more in the second-line and the first-line were 71. 4% and 52. 4%, respectively, with a tendency to be higher in the second-line. When creatinine values increased by 25%or more, even though they were within normal limits, following the CDDP+VNR in the first-line, the occurrence of neutropenia at grade 3 or more was significant (p=0. 016) in the first-course of the second-line therapy comprising CBDCA+PTX. The present findings suggest that when CBDCA+PTX therapy is performed following CDDP+VNR therapy, renal functions must be observed carefully, including changes in creatinine, during the CDDP+VNR therapy. When doses are determined for CBDCA+PTX as second-line therapy, dose reduction may be one of methods used to avoid serious hematological toxicity.

[Clinical evaluation of calculating carboplatin doses using modification of diet in renal disease (MDRD) estimate and adverse events].

A modified diet in renal disease (MDRD), a formula to estimate glomerular filtration rate (GFR), was proposed by Levey in 2006. In this study, we compared the dosage of carboplatin (CBDCA) calculated using MDRD with that calculated by conservative creatinine clearance (Ccr), and investigated the actual dosage given and the incidence of its adverse effects. In the 101 patients undergoing chemotherapy including CBDCA, the dosage calculated from the estimated GFR was 16% lower than that based on the estimated Ccr. This difference was greater in those under 65 years, women and those with a body mass index (BMI) > or =25. The most prominent incidence of adverse effects was thrombocytopenia in patients with lung cancer. In men, a serum creatinine level of > or =0. 6 mg/dL, GFR of <50 mL/min/1. 73 m(2) and a combined use of gemcitabine were cited as the factors responsible for the development of thrombocytopenia. It was concluded that the MDRD formula is an effective tool for evaluating patients with impaired renal function. It was suggested, on the other hand, that the dosage for medication should be decided by giving due consideration to factors other than renal functions.