Safety evaluation of lenvatinib treatment after atezolizumab plus bevacizumab therapy for patients with unresectable liver cancer: A comparison of lenvatinib as 1st­ or 2nd­line treatment.

Atezolizumab plus bevacizumab (Atez/BV) as first-line therapy and lenvatinib (LEN) as second-line therapy are the recommended treatments for patients with unresectable hepatocellular carcinoma. Adverse immune events caused by immune checkpoint inhibitors (such as Atez) generally only occur several months after administration; therefore, the potential influence of the first-line treatment on second-line treatment is not clear. The present study investigated the safety of second-line LEN treatment (2nd LEN) by comparing the adverse events (AEs) of 2nd LEN after first-line Atez/BV treatment for unresectable liver cancer, with those of first-line LEN treatment (1st LEN). Patients who received Atez/BV as first-line therapy and 2nd LEN, or those who received 1st LEN at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and September 2023 were retrospectively evaluated for treatment duration and AEs. The median treatment duration for patients in the 1st LEN (n=39) and 2nd LEN (n=13) groups was 151.0 days [95% confidence interval (CI) 77-303 days] and 128.5 days (95% CI 68-270 days), respectively (P=0.385). A greater proportion of patients showed elevated aspartate aminotransferase/alanine aminotransferase levels in the 2nd LEN group (76.9%) compared with those in the 1st LEN group (46.2%) (P=0.016). Hypothyroidism was more common in those receiving 2nd LEN (46.2%) than 1st LEN (12.8%) (P=0.016). In addition, grade 1 (three patients) and grade 2 (three patients) hypothyroidism was observed in patients receiving 2nd LEN. For these six patients, during first-line Atez/BV treatment, four patients had grade 0 hypothyroidism and two patients had grade 1 hypothyroidism (P=0.025). In conclusion, patients receiving 2nd LEN after treatment with Atez/BV are at an increased risk of hypothyroidism.

Relationship between Anaplastic Lymphoma Kinase (ALK) Inhibitors and Epileptic Seizure Disorder: A Post-Marketing Surveillance Study.

INTRODUCTION: ALK has been to be involved in the uptake and regulation of D2R, a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures. METHODS: This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the FAERS. The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined HLGT: ''Seizures (incl subtype)'' including HLT: ''Seizures and seizure disorders NEC.'' This study used the IC, a signal score, as a Bayesian statistical method for disproportionality analysis. RESULTS: The signal scores of ''Seizures and seizure disorders NEC'' for each ALK inhibitor were crizotinib (IC: -0.00052, 95%CrI: -0.38-0.27), ceritinib (IC: 1.18, 95%CrI: 0.68-1.54), alectinib (IC: 0.68, 95%CrI: 0.19-1.02), brigatinib (IC: 1.04, 95%CrI: 0.32-1.54), and lorlatinib (IC: 0.82, 95%CrI: 0.11-1.32). On the other hand, ''Generalized tonic-clonic seizures'', ''partial simple seizures NEC, '' ''Absence seizures,'' and ''partial complex seizures'' had no or few reported cases, and no signal was detected. CONCLUSION: To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures.

Comparison of Safety and Treatment Continuity of Palbociclib and Abemaciclib for Hormone Receptor-Positive, HER2-Negative Metastatic/Recurrent Breast Cancer.

Background: Appropriate adverse event (AE) management and maintenance of therapeutic intensity are necessary to achieve therapeutic benefits of CDK4/6 inhibitors (palbociclib and abemaciclib) in hormone receptor-positive, HER2-negative metastatic/recurrent breast cancer. Objective: This study was aimed at clarifying the effect of AEs associated with palbociclib and abemaciclib on treatment. Methods: A total of 62 and 49 patients were prescribed palbociclib and abemaciclib, respectively, at our hospital from January 1, 2018 to June 30, 2023. The rate and reasons for treatment discontinuation, interruption of administration, and changes in dose and dosing schedule, treatment duration, and relative dose intensity (RDI) were compared between the groups of patients prescribed the 2 treatments. Results: Treatment discontinuation due to AEs occurred more frequently with abemaciclib (12 patients) because of interstitial lung disease and hepatic and renal events than with palbociclib (5 patients; P = .008). Administration was interrupted in 57 (91.9%) and 35 (71.4%) patients treated with palbociclib and abemaciclib, respectively (P = .004). Dose reduction occurred in 37 (67.3%) and 19 (47.5%) patients treated with palbociclib and abemaciclib, respectively (P = .053). The median [range] treatment duration was 301 [21-1643] days for palbociclib and 238 [70-1526] days for abemaciclib (log-rank test, P = .581). The median RDI was 59.7% and 59.6% for palbociclib and abemaciclib, respectively (P = .539). Although the AEs of palbociclib and abemaciclib affected the treatment considerably, the treatment duration and RDI were similar. Conclusion: CDK4/6 inhibitors should be selected based on the tolerability and manageability of each AE.

Association between CDK4/6 inhibitors and drug-related osteonecrosis of the jaw: A pharmacoepidemiological study using the FDA Adverse Events Reporting System.

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.

Vancomycin-Induced Neutropenia With Subsequent Perioperative Readministration: A Case Report.

Vancomycin (VCM), an essential antibiotic for antimicrobial-resistant Gram-positive cocci, can lead to complications such as neutropenia. Here, we present a case of a 25-year-old male with noncommunicating hydrocephalus due to an intraventricular tumor who developed neutropenia during VCM therapy. Despite the suspected VCM-induced neutropenia, short-term readministration was deemed necessary for perioperative infection prophylaxis. This patient was readministered without neutropenia. A review of the literature revealed an earlier onset of VCM-induced neutropenia than that previously reported, emphasizing the importance of vigilant monitoring. Although readministration of VCM in patients with neutropenia is uncommon, it may be feasible with careful risk assessment, particularly in cases of mild neutropenia and short-term therapy. However, the mechanisms underlying VCM-induced neutropenia remain unclear, necessitating further research on the optimal management strategies.

Evaluation of Atezolizumab Plus Bevacizumab Versus Modified Lenvatinib Therapy in Child-Pugh A Unresectable Hepatocellular Carcinoma.

Background/Aim: Atezolizumab/bevacizumab (Atez/BV) and lenvatinib (LEN) are the recommended first-line treatments for patients with unresectable hepatocellular carcinoma (HCC). Previous reports have suggested that the tolerability and therapeutic efficacy of LEN could be enhanced by modifying its administration method. Therefore, this study compared the efficacy and safety of Atez/BV, the standard LEN therapy (standard LEN), and modified LEN therapy (modified LEN). Patients and Methods: The overall survival (OS) and the rate of discontinuation due to adverse events (AEs) were compared between groups treated with Atez/BV (n=36), standard LEN (n=30), and modified LEN (n=11). Results: Discontinuation due to AEs was required in 22.2%, 23.3%, and 9.1% of patients in the Atez/BV, standard LEN, and modified LEN groups (p=0.485). The median OS for the Atez/BV, standard LEN, and modified LEN groups was 523 [95% confidence interval (CI)=163-818], 382 (95%CI=330-547), and 604 (95% CI=257-656) days, respectively (log-rank test, p=0.949). Conclusion: Atez/BV and the standard and modified LEN regimens showed comparable efficacy and safety.

Evaluation of long-term pharmacist-led prospective audit and feedback in antimicrobial stewardship: An 8-year study.

BACKGROUND: Limited research has evaluated the long-term outcomes of prospective audit and feedback (PAF) led by pharmacists. We assessed pharmacist-led PAF processes and outcome measures over 8 years. METHODS: This study was conducted at a single public hospital in Japan. Between 2014 and 2021, pharmacists conducted weekday PAFs for hospitalized patients and annually evaluated the process and outcome measures. The endpoints included detection of drug-resistant bacteria, drug susceptibility rates, duration of antimicrobial therapy, and proportion of long-term administration. RESULTS: Among inpatients, methicillin-resistant Staphylococcus aureus significantly decreased from 50.9% in 2014 to 32.8% in 2021 (P < .001). The susceptibility rate of Pseudomonas aeruginosa to meropenem significantly increased from 91.2% in 2014 to 94.4% in 2021 (P < .001) and levofloxacin increased from 84.9% in 2014 to 89.3% in 2021 (P < .001). Antimicrobial therapy duration did not differ significantly between 2014 and 2016, but decreased significantly from 2017 onwards (P < .001), except in 2018. The number of patients receiving intravenous antimicrobials for >10 days decreased significantly between 2014 and 2021 (P < .001). CONCLUSIONS: Long-term continuous PAF interventions by pharmacists contribute to improving and maintaining process and outcome indicators and prevent the spread of drug-resistant bacteria.

Pituitary-Related Adverse Events and Onset Patterns Caused by Immune Checkpoint Inhibitors: Analysis Using the Japanese Adverse Drug Event Report Database.

Background and Objectives: One type of immune-related adverse event caused by immune checkpoint inhibitors (ICIs) is pituitary-related adverse events. The management of pituitary-related adverse events is important because they can be fatal if not treated promptly. Therefore, this study was conducted to investigate the onset of pituitary-related adverse events using the Japanese Adverse Drug Report (JADER) database. Materials and Methods: Cases registered in the JADER database from 2004 to 2019 were used. The target drugs were ipilimumab, nivolumab, pembrolizumab, avelumab, atezolizumab, and durvalumab, and the target adverse events were the high-level terms "Anterior pituitary hypofunction," "Anterior pituitary hyperfunction," "Posterior pituitary disorder," and "Pituitary neoplasm" in the Medical Dictionary for Regulatory Activities, Japanese version (MedDRA/J). The information component (IC) was used for signal detection and IC delta (ICΔ) was used for women-related signals. Onset timing and patterns were analyzed using the Weibull distribution. Results: Signals were detected with ipilimumab, nivolumab, pembrolizumab, and atezolizumab in "Anterior pituitary hypofunction," with ICs and 95% credible intervals (95%CrI) of 5.53 (5.30-5.69), 4.96 (4.79-5.08), 4.04 (3.76-4.25), and 2.40 (1.53-3.00). Significant signals were detected in women, except for atezolizumab. Additionally, the time of onset was classified as the wear-out failure type. Inverse signals were detected with ipilimumab and nivolumab in "Posterior pituitary disorder," with ICs (95%CrI) of -1.24 (-2.80--0.26), and -0.89 (-1.64--0.37). Conclusions: Anterior pituitary hypofunction is likely to occur with the long-term administration of ipilimumab, nivolumab, and pembrolizumab. Further investigation is needed to determine the differences in the tendencies to detect signals in the anterior and posterior pituitaries between ipilimumab and nivolumab.

Evaluation of the therapeutic effects and tolerability of modified lenvatinib administration methods for unresectable hepatocellular carcinoma: A preliminary study.

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor, is a standard therapeutic agent for hepatocellular carcinoma, but the high incidence of adverse events (AEs) related to LEN treatment often necessitates treatment discontinuation. The present study aimed to clarify the therapeutic efficacy and tolerability of modified LEN dosing methods, such as alternate-day dosing, necessitated by AEs of LEN. A total of 66 patients who received LEN at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and January 2022 were retrospectively evaluated. These patients were divided into those who completed treatment with the standard administration method (standard LEN, n=48) and those who changed from the standard administration method to a modified administration method in the middle of treatment [modified LEN (weekends off/alternate days), n=18]. The treatment duration and reasons for discontinuation of LEN treatment were analysed. The discontinuation rate due to AEs in the modified LEN group (1 patient) was less compared with that in the standard LEN group (16 patients) (P=0.022). The median treatment duration for patients in the standard LEN (n=48), modified LEN (weekends off, n=6) and modified LEN (alternate days, n=12) groups was 71 [95% confidence interval (CI) 55-134], 483 (95% CI: 193-644) and 222 (95% CI: 98-303) days, respectively (P=0.044). Modification of the administration method ensured fewer AE-related treatment discontinuations. However, weekends off dosing showed a longer treatment duration compared with standard dosing, whereas alternate day dosing showed no difference from standard dosing.

Analysis of adverse events leading to dose reduction/interruption of lenvatinib treatment in patients with Child-Pugh B unresectable hepatocellular carcinoma.

INTRODUCTION: We aimed to compare the safety of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma (HCC) in patients with Child-Pugh A (CP-A) and Child-Pugh B (CP-B) and to determine the adverse events (AEs) that cause dose reduction/interruption of treatment in patients with CP-B. METHODS: Sixty-six patients with lenvatinib as a first-line treatment for HCC at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and January 2022 were retrospectively evaluated. We analyzed the treatment duration, AEs, and reasons for dose reduction/interruption associated with lenvatinib treatment in patients with CP-A and CP-B HCC. RESULTS: The CP-B group had significantly more cases of grade ≥ 2 fatigue and anorexia than the CP-A group (p = 0.045 and p = 0.042, respectively). Regarding AEs that caused dose reduction/interruption of treatment, the CP-A group had significantly more cases of proteinuria than the CP-B group (p = 0.015), whereas the CP-B group had significantly more cases of hand-foot syndrome (HFS) than the CP-A group (p = 0.013). CONCLUSION: Patients with CP-B have greater difficulty than patients with CP-A in continuing treatment with repeated dose reductions/interruption of treatment due to intolerable grade ≥ 2 AEs (fatigue and anorexia). HFS is more likely to cause dose reduction/interruption of treatment in CP-B than in CP-A unresectable HCC.

[Investigation of Factors Related to Overall Survival in Patients Treated with Gemcitabine plus Paclitaxel(Albumin Suspension)for Advanced or Recurrent Pancreatic Cancer].

In cancer chemotherapy, identifying factors that may affect overall survival is clinically beneficial. In this study, we examined the factors associated with overall survival in patients treated with gemcitabine plus paclitaxel(albumin suspension) (GN)for pancreatic cancer. We included 91 pancreatic cancer patients who underwent GN therapy as the first-line treatment from January 2015-November 2021. In addition to survival from the start of therapy, the factors surveyed were patient background(gender, age, BMI, etc), dose at the start of treatment, baseline laboratory values, presence or absence of neutrophil count reduction, and modified Glasgow Prognostic Score(mGPS). Multivariate analysis showed that a neutrophil count reduction of Grade 3 or higher(p=0.004)and mGPS≤1(p=0.004)significantly increased overall survival. Consequently, 54.9% of patients(50/91)showed a neutrophil count reduction of Grade 3 or higher, and 35.2% of patients (32/91)showed expression of the first course. The study suggests that neutrophil count reduction of Grade 3 or higher and mGPS≤1 are indicators of prolonged overall survival. In particular, neutrophil count reduction had a high incidence in the first course; therefore, appropriate management is required from early stages of treatment. In addition, nutritional support care should be considered prior to starting treatment.

[Comparative Safety Assessment of Ramucirumab plus FOLFIRI and Bevacizumab plus FOLFIRI in Second- and Later-Line Treatment in Japanese Patients with Metastatic Colorectal Carcinoma].

The addition of anti-angiogenic agents to cytotoxic agents to improve outcomes has become the standard treatment for metastatic colorectal carcinoma. In this study, we evaluated the safety of bevacizumab plus FOLFIRI with that of ramucirumab plus FOLFIRI in second- and later-line treatment in Japanese patients with metastatic colorectal carcinoma. Patients who received ramucirumab or bevacizumab as a second- and later-line treatment between January 2016 and March 2020 were included. Treatment regimens, body surface area, dosage, number of treatment courses, and adverse events( AEs) were evaluated. There were 66 and 17 patients in the bevacizumab plus FOLFIRI and ramucirumab plus FOLFIRI groups, respectively. All patients developed AEs. AEs of grade 3/4 were documented in 84.8% and 100% of the patients in the bevacizumab plus FOLFIRI and ramucirumab plus FOLFIRI groups, respectively. Progressive disease was the most common reason for treatment discontinuation in both groups. Twelve (18.2%) and 5 (29.4%) patients in the bevacizumab plus FOLFIRI and ramucirumab plus FOLFIRI groups, respectively, discontinued treatment due to AEs. The most common AEs leading to discontinuation were malaise and decreased performance status. The findings of our study indicated that both bevacizumab plus FOLFIRI and ramucirumab plus FOLFIRI groups have a high incidence of AEs, and that medical professionals need to be aware of the frequent development of malaise and decreased performance status.

Elucidation of optimal proteinuria management based on the risk of ramucirumab-induced proteinuria.

Proteinuria is a dose-limiting adverse effect of ramucirumab treatment, which is an anti-angiogenic agent that targets the human vascular endothelial growth factor. The predictors of proteinuria have not been completely elucidated and there is currently no consensus. The present study aimed to identify the risk factors for ramucirumab-induced proteinuria and to determine an optimal proteinuria management. A total of 145 patients who received ramucirumab at Ogaki Municipal Hospital (Ogaki, Japan) between September 2015 and March 2021 were retrospectively studied. Multivariate logistic regression analysis was conducted to evaluate the association between the patient baseline characteristics and the development of proteinuria following ramucirumab treatment. Furthermore, the time of proteinuria onset and of the worst qualitative proteinuria were recorded. Proteinuria (>2+) following ramucirumab was independently associated with lung cancer [odd ratio (OR): 0.232, 95% confidence interval (CI): 0.061-0.874; P=0.031] and proteinuria at the start of treatment [qualitative test (+/-); OR: 4.760, 95% CI: 1.360-16.700; P=0.041]. The median time of onset of proteinuria was 56 days (time range, 7-414 days), and the median time when the worst qualitative results were observed was 83 days (time range, 7-442 days). The >2+ proteinuria in the qualitative test was observed in 27 out of the 82 patients with gastric cancer (P=0.041), 8/21 patients with colon cancer (P=0.188), and in 3 out of the 37 patients with lung cancer (P=0.003). The prevalence of proteinuria was low in patients with lung cancer, and proteinuria (>2+) was likely to occur when the proteinuria at the start of ramucirumab was (+/-) by qualitative test. The results from the present study indicated that particular attention should be paid to proteinuria at the start of treatment when monitoring proteinuria as an adverse event of ramucirumab treatment.

Risk-benefit Analysis of FOLFIRI Plus Ramucirumab/Aflibercept as a Third-line Treatment in Metastatic Colorectal Cancer.

BACKGROUND/AIM: The efficacy of folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus ramucirumab (F-RAM) or aflibercept (F-AFL) as a second-line treatment in metastatic colorectal cancer (mCRC) is established. In this study, the risks and benefits of F-RAM/AFL as a third-line treatment after first- and second-line bevacizumab for mCRC were evaluated. PATIENTS AND METHODS: Overall survival (OS) and adverse events (AEs) were compared between groups treated with F-RAM/AFL (n=17) and trifluridine/tipiracil combination tablet (TAS-102) (n=26). RESULTS: Median OS was longer in the third-line F-RAM/AFL group (379 days; 95%CI=157-458 days) than in the TAS-102 group (183 days; 95%CI=80-204 days) (log-rank test, p=0.015). Discontinuation due to AEs was only observed in the F-RAM/AFL group (3 cases). CONCLUSION: As a third-line treatment for mCRC, F-RAM/AFL should be prioritized over TAS-102 in terms of efficacy; however, the risk of AEs should be considered.

Effects of Type of Antibody to EGFR and Hypomagnesemia on Overall Survival in First-line Treatment of Patients With Unresectable Advanced/Recurrent Colorectal Cancer.

AIM: To clarify the differences in overall survival (OS) depending on the presence or absence of hypomagnesemia and the type of epidermal growth factor receptor antibody as first-line therapy for metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We retrospectively compared the OS in 68 patients who received cetuximab or panitumumab for mCRC at Ogaki Municipal Hospital (Ogaki, Japan) between January 2010 and December 2019. RESULTS: The complete and partial response rates in the cetuximab and panitumumab groups were 60.0% and 72.0%, respectively (p=0.470). The OS was significantly longer in the panitumumab group (median=1,007 days, range=208-1,433 days) than in the cetuximab group (median=735 days, range=181-2,391 days; p=0.047). Hypomagnesemia did not contribute to differences in OS in the two groups. CONCLUSION: Panitumumab may lead to a longer OS than cetuximab as first-line treatment of mCRC. The presence or absence of hypomagnesemia in cetuximab- or panitumumab-treated patients did not affect OS.

Identifying optimal magnesium replenishment points based on risk of severe hypomagnesemia in colorectal cancer patients treated with cetuximab or panitumumab.

PURPOSE: Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR). Treatment with cetuximab and panitumumab commonly causes hypomagnesemia, and optimal management of this adverse effect remains unclear. Here, we evaluated the optimal magnesium replacement points based on the risk of severe hypomagnesemia in colorectal cancer patients who received cetuximab or panitumumab. METHODS: We retrospectively evaluated 184 patients who received cetuximab or panitumumab for colorectal cancer at Ogaki Municipal Hospital (Ogaki, Japan) between January 2010 and December 2019. Univariate analyses were conducted to evaluate the relationship between patient baseline characteristics and development of hypomagnesemia following cetuximab or panitumumab treatment. Variables that were significantly associated with hypomagnesemia in the univariate analyses as well as previously reported risk factors were entered into a multivariate logistic regression model. RESULTS: The incidence of hypomagnesemia was associated with panitumumab treatment, pre-replenishment serum magnesium concentration, treatment duration, and treatment line. Severe hypomagnesemia post-cetuximab or panitumumab treatment was significantly associated with low baseline magnesium concentrations (< 1.8 mg/dL; odds ratio 18.100, 95% confidence interval 1.570-210.000; p = 0.020) and low serum magnesium concentrations during treatment (< 1.1 mg/dL; odds ratio 93.800, 95% confidence interval 3.510-2510.000; p = 0.007). CONCLUSION: To minimize the risk of severe hypomagnesemia during anti-EGFR treatment, magnesium replenishment should be initiated in patients with pre-replenishment concentrations of < 1.8 mg/dL, preferably before reaching intra-treatment concentrations of < 1.1 mg/dL.

Risk Benefit of FOLFIRI Plus Ramucirumab as Third-line and Later-line Treatment of Metastatic Colorectal Cancer.

BACKGROUND/AIM: The aim of this study was to clarify the risk benefits of folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus ramucirumab (F-RAM) as third-line and later-line treatment for metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We compared the overall survival (OS), adverse events (AEs), and cost of F-RAM to those of trifluridine/tipiracil combination tablet (TAS-102). RESULTS: There was no significant difference in the median OS [6.1 (range=1.2-16.3) months vs. 6.1 (range=1.2-22.3) months; log-rank test, p=0.272] and treatment duration [4.0 (range=1.2-9.6) months vs. 3.5 (range=0.2-12.3) months, p=0.888] between the F-RAM (n=13) and the TAS-102 (n=36) groups. However, AEs were more frequent in the F-RAM group, and 1-year administration of F-RAM cost higher ($81,724.8 vs. $18,931.4, p<0.001). CONCLUSION: F-RAM as third-line and later-line treatment for mCRC has a poor risk benefit. TAS-102 should be given priority over F-RAM.

A comparative study of nivolumab and axitinib in terms of overall survival, treatment continuation, and cost for patients with metastatic renal cell carcinoma.

Nivolumab and axitinib has recommended as a second-line treatment in patients with metastatic renal cell carcinoma (mRCC) after tyrosine kinase inhibitor treatment. In this study, overall survival (OS), treatment continuation, and the cost of nivolumab and axitinib-the second-line treatment agents for mRCC-were compared and examined. Herein, we retrospectively surveyed patients with pathologically confirmed mRCC, treated with nivolumab (n=9) or axitinib (n=16) at Ogaki Municipal Hospital (Ogaki, Japan) between January 2012 and May 2019. The treatment periods for the nivolumab- and axitinib-administered groups were 5.4 (range: 1.4-21.3) and 3.4 (range: 0.3-28.1) months, respectively (P=0.089). The postponement periods for the nivolumab- and axitinib-administered groups were 7 (range: 0-186) and 0 (range: 0-262) days, respectively, and the difference was statistically significant (P=0.008). The median OS for patients treated with nivolumab and axitinib was 12.3 (range: 1.5-25.5 months) and 9.2 (range: 2.2-55.0 months) months, respectively (P=0.633). The one-year cost estimates for axitinib and nivolumab in clinical practice were $60,694.2 and $86,544.4, respectively (P=0.017). We found that despite frequent interruptions in nivolumab administration and a longer postpaonement period for the nivolumab-administered group than for the axitinib-administered group, both groups exhibit comparable treatment duration and OS.

[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.

[A Survey of Health Food Use and Patient Satisfaction among Patients Undergoing Cancer Pharmacotherapy].

This study aimed to clarify the situation of use of health foods by patients and the level of satisfaction of patients in order to make use of information on cases where patients undergoing cancer medication therapy use health foods. Between May 7, 2018 and June 29, 2018, we conducted a questionnaire survey of patients with progressive cancer who were undergoing cancer chemotherapy at Ogaki Municipal Hospital. In addition, we conducted a multivariate analysis of patients who were using health foods and those who were not. The questionnaire items included the objectives of use, product effectiveness and satisfaction, and QOL. The rate of health food use was 81/281 (29.5%). The primary objectives of use were, "to maintain health" (29.8%) and "to alleviate symptoms" (24.0%). The primary sources of information about health foods were "a friend" (50.6%) and "TV" (13.5%). The satisfaction level was 0-3 points in 8.3% of patients, 4-6 points in 38.1% of patients, and 7-10 points in 53.6% of patients. For "stage of illness (recurrence)," the odds ratio was 1.810 (95% CI, 1.040-3.150; p=0.035), and for "QOL value," the odds ratio was 2.210 (95% CI, 1.220-4.020; p=0.009), indicating that these factors had a significant influence on health food use. Health foods tended to be used in patients who had recurring cancer with low QOL and various symptoms, and friends and other people close to the patient had a large influence on the patient's decision. It was clear that the patients' satisfaction level was high.