Predictors of abemaciclib discontinuation in patients with breast cancer: a multicenter retrospective cohort study.

OBJECTIVE: This study explored the predictors of abemaciclib discontinuation, a cyclin-dependent kinase 4 and 6 inhibitor, in patients with breast cancer. MATERIAL AND METHODS: Between November 2018 and March 2023, 147 patients with breast cancer treated with abemaciclib at Osaka Medical and Pharmaceutical University Hospital and Kindai University Nara Hospital were included. The exclusion criteria were as follows: lack of blood testing within 2 weeks prior to starting abemaciclib therapy, transfer to another facility after the commencement of abemaciclib therapy, and discontinuation of abemaciclib therapy due to the diagnosis of another cancer. The duration from the initiation of abemaciclib to discontinuation for any reason and to temporary suspension or dose reduction due to adverse events were analyzed as outcome variables using multivariate Cox regression analysis. RESULTS: Baseline weight < 54 kg, bone metastases, and hemoglobin level ≤ 12.4 g/dL were independent predictors of abemaciclib discontinuation for any reason. The main adverse events leading to abemaciclib discontinuation were liver enzyme elevation and gastrointestinal symptoms. Additionally, focusing on the adverse event of abemaciclib, a baseline weight < 54 kg was an independent predictor of temporary suspension or dose reduction due to adverse events. The most common adverse events leading to temporary suspension or dose reduction were neutropenia and diarrhea. CONCLUSION: Patients with lower body weight are more susceptible to the adverse events of abemaciclib, increasing their risk of treatment discontinuation. In such patients, strict monitoring of adverse events and consideration of more frequent medical visits are necessary from the start of abemaciclib therapy.

Platelet count and dose, but not comorbidities, predict severe neutropenia in cabazitaxel-treated prostate cancer patients: A retrospective observational study.

OBJECTIVE: To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. MATERIALS AND METHODS: Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. RESULTS: Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n = 19), followed by dyslipidemia (n = 14) and diabetes (n = 11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels < 22.4×104/µL and those receiving cabazitaxel doses > 34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. CONCLUSION: Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.

Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study.

BACKGROUND: The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC). METHODS: mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups. RESULTS: We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01). CONCLUSION: Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.

Predictors of olaparib discontinuation owing to adverse drug events in patients with ovarian, peritoneal, or fallopian tube cancer: a retrospective observational study.

We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2-3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.

[Serotonin syndrome in a patient with small cell lung cancer].

The patient was a 67-year-old male who had been treated for several years with 150 mg fluvoxamine maleate due to depression. He visited our hospital with primary symptoms of swelling of the right upper extremity and dyspnea in August, XXXX. As a result of examinations, he was diagnosed with stage IIIB extended small cell lung cancer(T4N3M0). One course of carboplatin/etoposide(CBDCA/VP-16)therapy was started on October 1. Since the tumor size was reduced, thoracic effusion disappeared, and superior vena cava syndrome was alleviated, the therapy was changed to cisplatin/irinotecan (CDDP/CPT-11)on October 23, and the 3rd course was initiated on November 22. Anxiety and tremor appeared on the 4th day of the 3rd course and because they were exacerbated, and myoclonus appeared, a diagnosis of serotonin syndrome was made on the 38th day, and the administration of fluvoxamine maleate was discontinued. The symptoms were alleviated after the discontinuation, and the 4th course could be implemented. In this patient, serotonin syndrome was considered to have been induced by serotonin secretion promoted by the CDDP administration, and by serotonin in the brain increasing abnormally due to the SSRI.

Effects of additives and electrolytic treatment to remove tritium from contaminated water.

As a method for separating tritiated water from radioactively contaminated water, an additive was mixed into the contaminated water and their treatments of agitation/circulation and electrolytic was considered to improve of the separation efficiency. Carbide powder and ore (silica stone) powder were used as additives. The radioactivity concentration of the tritium-contaminated water (tritiated water; HTO) was 366 Bq/mL before treatment, however it obtained 333 Bq/mL and decreasing rate of 9.02%, and a high separation efficiency after treatment. Furthermore, in the reproducibility experiments (five times) using high content of HTO, the average HTO/H2O separation efficiency was obtained about 5.59% indicating good reproducibility. The agitation/circulation treatment process was dissociated and ionized HTO, and was prepared colloidal particles by OT- and 3T+. In the electrolytic treatment process, the colloidal particles in HTO were deposited on the both electrodes applied DC voltage, and was efficiently removed tritium. These treatment processes using additives were found to be useful for removal of tritium.