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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. [ABSTRACT FROM AUTHOR]

Pomalidomide (POM) is a second-generation immunomodulatory agent with proven efficacy in patients with relapsed/refractory multiple myeloma (RRMM) proven to be refractory to previous treatment with lenalidomide (LEN) and bortezomib. We herein conducted a retrospective analysis of 14 RRMM patients receiving POM to determine its tolerability and safety in the clinical setting. The median age of the patients was 72 years (range, 58–84 years), and 85.7% of the patients were aged >70 years. The most frequent treatment dose was 3 mg/day. POM dose reductions were required in 54.5% (6/11) of the patients. The patient data were compared among three age groups (<70, 70–75 and >75 years) and there was only significant difference in daily POM treatment dose. The tolerability of POM must be confirmed, particularly in elderly patients. Dose reduction from 4 to 3 mg occurred during the second cycle in 83.3% (5/6) of the patients. It is important to determine the tolerability of POM in the early phases of treatment. The most frequently reported grade 3/4 hematological adverse events were neutropenia (64.3%), anemia (64.3%) and thrombocytopenia (57.1%). Although the median number of treatment cycles was 4 (range, 1–13), 21.4% (3/14) of the patients with a performance status (PS) of 3 were administered only 1 treatment cycle. The tolerability of POM was low among patients with poor PS and an aggressive treatment introduction should be avoided. However, 21.4% (3/14) of the patients were able to continue treatment for >1 year and some patients received long-term therapy. POM does not require dose modification for renal function, and multiple capsule doses are available, which is an advantage of POM compared with LEN. POM may be administered to late-stage RRMM patients in a real-world clinical setting, but elderly patients or those with poor PS must be treated with caution. In this manner, the treatment options for RRMM patients may be expanded by assessing the tolerability and safety of POM. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the effect of the timing of treatment discontinuation on the prognosis of patients with advanced and recurrent gastric cancer chemotherapy. Between July 2014 and March 2017, 127 patients who underwent chemotherapy for advanced and recurrent gastric cancer at Ogaki Municipal Hospital (Ogaki, Japan) were examined. To determine factors associated with survival, multivariate analysis using the Cox proportional hazards model, and hazard ratios and their 95% confidence intervals (95% CI) were calculated. The reasons for discontinuation of last-line chemotherapy and the last hospitalization prior to mortality were surveyed. Age (≤51 years), number of treatment lines (≤1 line), and days between last dose of the final chemotherapy regimen and death (≤79 days) were independently and significantly associated with survival in the multivariate analysis. Compared with patients who did not receive chemotherapy in the last 79 days of life, those who received chemotherapy in the last 79 days of life days had a hazard ratio of 1.858 (95% CI, 1.059–3.261; P=0.031) for mortality. A decrease in the performance status was responsible for treatment discontinuation in 51 of 75 cases among patients who received chemotherapy in the last 79 days of life and 9 of 26 cases among patients who did not receive chemotherapy in this duration (P<0.001). Among patients who received chemotherapy in the last 79 days of life, 67 patients were hospitalized prior to mortality; among patients who did not receive chemotherapy in this duration, 15 patients were hospitalized prior to mortality (P<0.001). In conclusion, continuation of chemotherapy until just prior to mortality does not prolong the survival time in patients with advanced and recurrent gastric cancer. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the incidence of tumor lysis syndrome (TLS) in patients with hematological malignancies treated with rasburicase, and to evaluate the dose and duration of rasburicase administration. A total of 52 patients were enrolled. The background of the patients, incidence of TLS and laboratory data were retrospectively examined; in addition, the dose and duration of rasburicase administration and the factors affecting the onset of TLS were evaluated and compared among TLS risk categories. During the study period, 2 (3.8%) of the patients developed clinical TLS and 24 (46.2%) developed laboratory TLS (LTLS). Although the LTLS rate was very high, there were no life-threatening cases of TLS. The median daily dose of rasburicase administered to all patients was 7.5 mg/day (interquartile range, 7.5-9.0 mg/day), and the daily weight-based dose was 0.147 mg/kg/day (range, 0.126-0.178 mg/kg/day). The administration duration was 3 days (interquartile range, 3-4 days). Additionally, there was no significant association between TLS risk classification and daily rasburicase administration dose, duration, or post-administration laboratory data. The factors affecting the onset of TLS included serum uric acid level, as well as serum creatinine and phosphate levels. Rasburicase was highly effective in the prevention and management of hyperuricemia, even at a low-dose (7.5 mg/day) and a duration that was 3 days shorter compared with that recommended by the manufacturer. Therefore, clinicians should administer rasburicase based on their clinical judgment, taking into consideration the cost-effectiveness of this therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

S-1 adjuvant chemotherapy is an outpatient treatment for gastric cancer. To evaluate the role of the pharmacist outpatient service in increasing medication adherence and reducing adverse events associated with S-1, the present study retrospectively analyzed prescription recommendations from pharmacists to physicians and the persistence rate of S-1 adjuvant chemotherapy use in patients with gastric cancer. A total of 40 subjects who utilized the pharmacist outpatient service between November 2014 and March 2016 comprised the pharmacist group; and 94 patients who underwent S-1 adjuvant chemotherapy for gastric cancer between September 2012 and October 2014, but not as pharmacist outpatients, comprised the control group. Data on the prescription recommendations, persistence rate of S-1 adjuvant chemotherapy for 1 year and relative dose intensity were collected. The number of interventions and consultations for the pharmacist outpatient group were 40 and 644, respectively. Prescription recommendations regarding dosage, drug administration interval, and supportive therapy were provided in 62, 15 and 132 cases, respectively. The prescription proposal acceptance rate was 92.5%. The persistence rate of S-1 adjuvant chemotherapy for 1 year was significantly higher in the pharmacist group (82.5%) compared with the control group (39.4%; P<0.0001). The discontinuation rate due to adverse events was significantly lower in the pharmacist group (7.5%) compared with the control group (31.9%; P=0.0015). In subjects who completed S-1 adjuvant chemotherapy, the relative dose intensities in the control and pharmacist groups were 82.9 and 84.7%, respectively. In conclusion, the continued pharmaceutical intervention ensured a high persistence rate of S-1 adjuvant chemotherapy.

The recommended chemotherapy regimens for pancreatic cancer include the combination of 5-fluorouracil/leucovorin, oxaliplatin and irinotecan (FOLFIRINOX), nab-paclitaxel (nab-PTX) plus gemcitabine (GEM), GEM alone and tegafur/gimeracil/oteracil potassium (S-1) alone. Although the cost-effectiveness of metastatic pancreatic cancer chemotherapies has been extensively investigated, to the best of our knowledge, no study has specifically compared the cost-effectiveness among FOLFIRINOX, nab-PTX + GEM, GEM and S-1 regimens to date. The aim of the present study was to examine the cost-effectiveness of these four regimens. The expected costs were calculated based on data from patients with metastatic pancreatic cancer who were treated with the FOLFIRINOX, nab-PTX + GEM, GEM alone or S-1 alone. The median survival time (MST) from randomized controlled trials in the literature was used to evaluate the therapeutic effect of these regimens. The cost-effectiveness ratio was calculated using expected costs and MST for these four regimens. The expected costs per patient for the FOLFIRINOX, nab-PTX + GEM, GEM or S-1 regimens were ¥6,361,191.4, ¥4,802,063.6, ¥540,091.4 and ¥528,514.6, respectively, and the cost-effectiveness ratios per month were ¥642,544.6/MST, ¥470,790.5/MST, ¥81,832.0/MST and ¥55,633.1/MST, respectively. In conclusion, the nab-PTX + GEM and FOLFIRINOX regimens were associated with a high therapeutic efficacy and high cost. The GEM regimen exhibited a lower therapeutic efficacy compared with the nab-PTX + GEM and FOLFIRINOX regimens, but the findings of this study indicated that the GEM and S-1 regimens were the most cost-effective regimens.

Comparison of the costs of capecitabine plus oxaliplatin (CapeOX) with that of FOLFOX6 (5-fluorouracil/leucovorin [LV] + oxaliplatin) as an adjuvant chemotherapy for stage II or III colorectal cancer has previously been reported. However, there are no reports comparing uracil and tegafur (UFT)/LV with capecitabine. Therefore, the current study compared the costs of adjuvant chemotherapy regimens including CapeOX, FOLFOX6, capecitabine and UFT/LV. The costs of chemotherapeutic drugs and for the prevention and treatment of adverse events were evaluated, as these account for the bulk of the treatment costs. Costs were expressed in Japanese Yen (US dollars). The mean costs of the chemotherapeutic drugs per patient, for an entire course of treatment, were ¥882,632 ($8,406) for UFT/LV, ¥353,290 ($3,365) for capecitabine, ¥1,436,218 ($13,678) for FOLFOX6 and ¥1,255,630 ($11,958) for CapeOX. The mean costs associated with adverse events per patient were ¥2,210 ($21) for UFT/LV, ¥6,749 ($64) for capecitabine, ¥173,432 ($1,652) for FOLFOX6 and ¥107,430 ($1,023) for CapeOX. Therefore, the capecitabine regimen contributes to reducing costs for the management of patients with colorectal cancer who have had surgery.

Regorafenib and trifluridine/tipiracil combination tablet regimens are standard third-line or later treatments for advanced and recurrent colorectal cancer with no significant difference in efficacy. The present study aimed to compare the cost-effectiveness of using regorafenib vs. the trifluridine/tipiracil combination tablet. The expected cost was calculated based on data from patients with advanced and recurrent colorectal cancer who were treated with regorafenib or trifluridine/tipiracil combination tablet. The median survival time (MST) from the CORRECT and the RECOURSE study was used to evaluate the therapeutic efficacy of the regimens. The cost-effectiveness ratio was calculated from the expected cost and MST for the two regimens. The expected cost per patient for the regorafenib and the trifluridine/tipiracil combination tablet regimen was ¥705,330.3 and ¥371,198.7, respectively, and the cost-effectiveness ratio was ¥110,207.9/MST and ¥52,281.5/MST, respectively. In conclusion, the findings of the present study demonstrated that the trifluridine/tipiracil combination tablet regimen is more cost-effective compared with the regorafenib regimen.

The aim of this retrospective study was to investigate the safety of S-1 as second-line therapy and to evaluate the association between neutropenia occurring during first-line gemcitabine (GEM) therapy and survival for advanced or recurrent pancreatic cancer (APC). Between January, 2010 and December, 2014, 123 APC patients received chemotherapy at the Ogaki Municipal Hospital (Ogaki, Japan). Of those, 37 received GEM as first-line and S-1 as a second-line therapy (GEM→S-1 group). A further 60 patients received GEM as first-line therapy, but did not receive second-line therapy (GEM group). The median overall survival in the GEM→S-1 (n=37) and GEM (n=60) groups was 323 days [95% confidence interval (CI): 138-218.9 days] and 172 days (95% CI: 105-184.4 days), respectively (P=0.0004). The median overall survival in the mild (grade ≤2; n=63) and severe (grade ≥3; n=34) neutropenia groups was 178 days (95% CI: 182-275 days) and 330 days (95% CI: 297-514 days), respectively (log-rank test, P=0.0023). The severe non-haematological toxicities associated with S-1 as second-line therapy were nausea (2.7%) and hand-foot syndrome (2.7%). Second-line S-1 treatment was discontinued due to adverse events in 5.4% (2/37) of the cases. In conclusion, neutropenia occurring during GEM therapy administered as first-line treatment to APC patients was strongly associated with a better prognosis. S-1 therapy as second-line treatment was associated with a low incidence of severe adverse events and the patients were able to successfully continue treatment.

The cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen is considered to be a standard treatment for non-Hodgkin's lymphoma (NHL). Patients receiving CHOP chemotherapy often experience febrile neutropenia (FN) due to myelotoxicity. The proper management of FN is essential to guarantee a positive outcome of the NHL treatment. Therefore, the present study retrospectively examined chemotherapy continuity and the incidence of FN during CHOP therapy in an outpatient setting. The subjects were 136 patients who received CHOP chemotherapy between January 2012 and December 2014. A total of 31 patients unable to be treated in an outpatient setting were excluded from the study. Of the remaining 105 patients, 73 patients who did not require hospitalization during the chemotherapy treatment were included in the non-hospitalized group, and 32 patients who required hospitalization during chemotherapy treatment were included in the re-hospitalization group. The numbers of patients from these two groups who completed the planned treatment were 71 and 24, respectively (P<0.01). In addition, the duration of granulocyte-colony stimulating factor (G-CSF) treatment was 5.3±1.22 and 6.1±1.46 days, respectively (P<0.01). The numbers of patients experiencing FN in an outpatient setting were 14 and 19, respectively (P<0.01). During administration of primary prophylaxis with G-CSF, the incidence of FN was 21.0% (22/105) in cycle 1. In conclusion, the present study has revealed a requirement to educate patients about infection prevention prior to the first cycle of chemotherapy. Patients who require the administration of long- term G-CSF are at risk of unplanned re-hospitalization, and treating them with polyethylene glycol G-CSF to reduce the number of required injections should be considered as an option. Therefore, proper supportive therapy and management of infection are important to safely treat patients with CHOP in an outpatient setting.

In the treatment of advanced or recurrent gastric cancer, the prolongation of survival depends on the use of second-line therapy, with paclitaxel (PTX) or irinotecan (CPT-11) as the key agents. The present study aimed to retrospectively investigate the safety and continuity of weekly PTX and CPT-11 monotherapy as second- or third-line treatment for advanced or recurrent gastric cancer. A total of 62 patients who had received PTX or CPT-11 for gastric cancer at the Ogaki Municipal Hospital (Ogaki, Japan) were retrospectively reviewed. Of the 47 patients who received PTX as second-line therapy, 13 (27.7%) received third-line therapy with CPT-11. Second-line PTX and third-line CPT-11 were discontinued due to progressive disease (PD) in 27 and 7 cases, respectively, and deterioration in the performance status (PS) in 20 and 4 cases, respectively. Only 1 case of discontinuation due to adverse events (AEs) was reported for third-line CPT-11. Furthermore, of the 15 patients who received CPT-11 as second-line treatment, 11 (73.3%) then received PTX as third-line treatment. Second-line CPT-11 and third-line PTX were discontinued due to PD in 9 and 6 cases, respectively, and deterioration in the PS in 4 and 5 cases, respectively, whereas there was only 1 case of discontinuation due to AEs for second-line CPT-11. Severe AEs for PTX and CPT-11 were infrequent; however, the frequency of diarrhea was high when PTX was administered as third-line therapy (63.6%), whereas the frequency of malaise was high when CPT-11 was administered as second- (73.3%) and third-line (76.9%) therapy. In conclusion, severe AEs due to PTX and CPT-11 as second- and third-line treatment for advanced or recurrent gastric cancer are infrequent and patients are generally able to continue treatment. However, the possibility of diarrhea with third-line PTX and malaise with second- and third-line CPT-11 treatment should be considered when planning chemotherapy.