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.

[A Case of Thrombocytopenia Following Minocycline Administration].

Drug-induced thrombocytopenia is associated with bleeding tendency and suggests the need for the immediate suspected drug withdrawal. Patients with drug-induced thrombocytopenia usually experience an acute drop in platelet (PLT) levels a week or two after starting a new medication. Thrombocytopenia has both immune and non-immune mechanisms. Minocycline (MINO)-induced thrombocytopenia is rare; thus, there are few studies of this condition. In the present study, intravenous administration of MINO led to thrombocytopenia. The female patient was 80 years old. She was receiving radiation therapy for tongue cancer and medication for pain control. She had fever and aspiration pneumonia and was being treated with an antibacterial drug. Empiric therapy consisting of intravenous administration of tazobactam/piperacillin was performed; however, inflammation and fever did not improve. The bacterial drug was changed to vancomycin and cefmetazole. Sputum culture was positive for Enterobacter cloacae thus, we changed her treatment to MINO. Seven days after starting MINO, PLT levels were low; however, they recovered when treatment was stopped. Our findings suggest that MINO may rarely cause severe thrombocytopenia; thus, it is necessary to observe the patient's blood collection.

The efficacy and safety of intravenous chlorpromazine treatment for sleep disturbance in patients with incurable cancer, with oral administration difficulty: a 1-week, prospective observational study.

BACKGROUND: Sleep disturbance is a common psychiatric disorder in patients with cancer. However, many patients with incurable cancer have difficulty receiving oral administrations, which limits treatment options during disease progression. The aim of the present study was to assess the efficacy and safety of intravenous chlorpromazine treatment for sleep disturbances in patients with incurable cancer, with oral administration difficulty. METHODS: A prospective observational study was conducted among 52 patients with incurable cancer, with oral administration difficulty received daily intravenous chlorpromazine treatment for sleep disturbance from 2018 to 2020 at a single-unit university hospital. St. Mary's Hospital Sleep Questionnaire (SMHSQ) compared sleep before and after intravenous chlorpromazine administration. The primary endpoint was the efficacy rate of sleep quality [defined as a score of ≥4 (range, 1-6)] 7 days after receiving chlorpromazine. RESULTS: Beginning the day after receiving chlorpromazine, sleep quality significantly improved from a mean score of 1.6±0.7 to 4.3±1.2, and 80.8% [95% confidence interval (CI): 66.5-89.1%] and 69.2% (95% CI: 53.8-79.6%) of patients reported good sleep quality 3 and 7 days after receiving chlorpromazine, respectively. The patients reported increased total sleep time and fewer awakenings during sleep, and satisfaction with sleep and difficulty falling asleep improved. Some adverse events occurred [akathisia (n=2), dry mouth (n=2), and somnolence (n=3)]; all were Grade 1 (CTCAE ver5.0) and improved with chlorpromazine discontinuation. Systolic blood pressure and heart rate displayed no clinically problematic changes. CONCLUSIONS: Intravenous chlorpromazine has a high tolerability and effectively treats sleep disturbances in patients with incurable cancer with oral administration difficulties.

[Effectiveness of a Low-dose Corticosteroid in a Patient with Polymyalgia Rheumatica Associated with Nivolumab Treatment].

Nivolumab, an anti-programmed cell death 1 antibody, has been approved for the treatment of unresectable advanced non-small-cell lung cancer (NSCLC). Although immune-related adverse events (irAEs) such as dermatologic, digestive, endocrine, hepatic, and pulmonary toxicities are known to occur upon administration of immune checkpoint inhibitors, case reports of polymyalgia rheumatica (PMR) associated with nivolumab use are rare. We report a case of an NSCLC patient who developed PMR during treatment with nivolumab and received corticosteroids. A 74-year-old man without a history of autoimmune diseases received nivolumab at a dosage of 3 mg/kg once every 2 weeks for the treatment of stage IIIB squamous cell carcinoma. After 12 cycles of nivolumab treatment, he developed grade 3 muscle pain and arthralgia, requiring hospitalization and discontinuation of nivolumab. A bone scintigraphy revealed no bone metastasis. Serological tests showed that although creatine phosphokinase did not increase, C-reactive protein and the erythrocyte sedimentation rate were both high. Tests for the rheumatoid factor, anti-cyclic citrullinated peptide antibody, and anti-nuclear antibody were negative. In addition to the serological findings, joint ultrasonography data and clinical symptoms were evaluated, leading to the diagnosis of PMR. Oral prednisolone 20 mg/d was started to treat the PMR without giant-cell arteritis. The patient's symptoms improved within 5 d of the initiation of treatment. Prednisolone was tapered to 5 mg/d without recurrence of PMR. Although grade 3 or 4 irAEs (except in type 1 diabetes) are generally treated with high-dose corticosteroids, grade 3 PMR associated with nivolumab use may be treatable with low-dose corticosteroids.

Intravenous Chlorpromazine for the Short-Term Treatment of Insomnia in End-Stage Cancer Patients With Difficulty in Oral Administration.

The objective of the study was to evaluate effectiveness and safety of intravenous chlorpromazine for the short-term treatment of insomnia in end-stage cancer patients. Insomnia occurs as one of distressing symptoms in 70% of end-stage cancer patients. End-stage cancer patients often have difficulty in oral administration because of disease progress. We retrospectively evaluated 30 end-stage cancer patients with difficulty in oral administration who received intravenous chlorpromazine for the short-term treatment of insomnia. A primary end point was sleep quality based on St. Mary's Hospital Sleep Questionnaire 3 days after the treatment. Improved sleep quality was observed on the day after the treatment and later (P < .001), and the effective rate mean was 0.63 (95% confidential interval: 0.45-0.81) 3 days after the treatment. Increased total sleep time and decreased sleep latency time were observed 3 days after the treatment (P < .001); however, no improvement in depth of sleep was achieved (P = .231). There was no adverse event except for two delirium cases. The study indicated that intravenous chlorpromazine can be applied safely and effectively for the short-term treatment of insomnia in end-stage cancer patients with difficulty in oral administration.

Factors Associated with the Effectiveness of Intravenous Administration of Chlorpromazine for Delirium in Patients with Terminal Cancer.

BACKGROUND: Delirium in patients with terminal cancer is irreversible and increases treatment resistance, which leads to a deterioration in quality of life. OBJECTIVE: To investigate factors affecting the effectiveness and safety of intravenous chlorpromazine for irreversible delirium in patients with terminal cancer. DESIGN/MEASUREMENTS: Multiple regression analysis for factors affecting treatment effectiveness was carried out based on a retrospective comparison between responders and nonresponders to intravenous chlorpromazine. SETTING/SUBJECTS: Ninety-seven patients with terminal cancer who were treated with intravenous chlorpromazine for irreversible delirium were included. RESULTS: The rate of patients with ≥50% improvement in mean Nursing Delirium Screening Scale score from pretreatment to day three of chlorpromazine treatment was 0.48 (95% confidence interval [CI]: 0.38-0.58). Factors affecting chlorpromazine treatment effectiveness were hyperactive delirium (odds ratio [OR]: 6.25, 95% CI: 1.14-34.5) and longer survival (OR: 1.096, 95% CI: 1.05-1.14). The mean chlorpromazine dose was low, at 17.9 mg/day. Adverse events were reported in 11 patients (11.3%) by day three of chlorpromazine treatment, and all were observed in patients who survived less than two weeks after chlorpromazine treatment. Patients who died, who had decreased blood pressure during chlorpromazine administration, and who showed acute akathisia all displayed shock index ≥1. CONCLUSIONS: Intravenous administration of low-dose chlorpromazine may be an effective and safe treatment option for delirium in patients with terminal cancer who have hyperactive delirium, longer predictive prognosis, and shock index <1.

Linear polystyrene-stabilized palladium nanoparticles-catalyzed C-C coupling reaction in water.

Linear polystyrene-stabilized PdO nanoparticles (PS-PdONPs) were prepared in water by thermal decomposition of Pd(OAc)(2) in the presence of polystyrene. The immobilization degree of palladium was dependent on the molecular weight of polystyrene, while the size of the Pd nanoparticles was not. Linear polystyrene-stabilized Pd nanoparticles (PS-PdNPs) were also prepared using NaBH(4) and phenylboronic acid as reductants. The catalytic activity of PS-PdONPs was slightly higher than that of PS-PdNPs for Suzuki coupling reaction in water. PS-PdONPs exhibited high catalytic activity for Suzuki and copper-free Sonogashira coupling reactions in water and recycled without loss of activity.

Facile preparation of linear polystyrene-stabilized Pd nanoparticles in water.

Palladium nanoparticles can be readily stabilized onto linear polystyrene by a simple procedure. The resultant polystyrene-stabilized Pd has high catalytic activity for Suzuki-Miyaura cross-coupling reaction in water and can be reused without loss of activity.