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1.
Invest New Drugs ; 38(4): 1200-1206, 2020 08.
Article in English | MEDLINE | ID: mdl-31823160

ABSTRACT

Purpose Anticancer agents are known to increase cancer-associated thrombosis (CAT) onset. CAT onset rate is reported to be 1.92% in cisplatin-based therapy, 6.1% in paclitaxel plus ramucirumab combination therapy, and 11.9% in bevacizumab monotherapy. Because immune checkpoint inhibitors (ICIs) cause a sudden increase in T cell number, an association between administration of these drugs and increase in CAT incidence is likely. However, the extent to which ICI administration affects CAT incidence remains unclear. Further, risk factors for CAT incidence have not yet been identified. The present study investigated CAT incidence and associated risk factors in patients receiving ICI. Methods Patients administered nivolumab or pembrolizumab at Fujita Health University Hospital from April 2017 to March 2018 were enrolled. We collected retrospective data regarding age, sex, cancer type, BMI, medical history, laboratory data at treatment initiation, medications, and computed tomography (CT) interpretations from electronic medical records. Results We identified 122 eligible participants from 135 patients receiving nivolumab or pembrolizumab. Ten patients (8.2%) developed CAT. A history of venous thromboembolism (VTE) or arterial thromboembolism (ATE) was a risk factor for CAT incidence (odds ratio: 6.36, P = 0.039). A history of heart disease may be a risk factor for CAT incidence (odds ratio 6.56, P = 0.052). Significantly higher usage of antiplatelet and anticoagulant therapy was noted in patients who developed CAT (60%) than in those who did not (13.4%, p < 0.01). Conclusion High (8.2%) CAT incidence during ICI administration suggested that ICI is not associated with a lower blood clot risk than other anticancer agents investigated in previous studies. For patients with VTE, ATE, or heart disease history, it is crucial to consider the possibility of CAT even with antiplatelet therapy.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Immune Checkpoint Inhibitors/adverse effects , Neoplasms/drug therapy , Nivolumab/adverse effects , Thrombosis/etiology , Aged , Anticoagulants/adverse effects , Female , Heart Diseases/epidemiology , Humans , Male , Middle Aged , Neoplasms/complications , Neoplasms/epidemiology , Platelet Aggregation Inhibitors/adverse effects , Retrospective Studies , Risk Factors , Thromboembolism/epidemiology , Thrombosis/epidemiology
2.
Biol Pharm Bull ; 43(4): 669-674, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-32037352

ABSTRACT

Despite in vivo studies suggesting that obesity increases carboplatin (CBDCA) bone marrow toxicity, the American Society of Clinical Oncology recommends that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer. Accordingly, the present study retrospectively investigated the effect of body mass index (BMI) on bone marrow toxicity in patients with gynecological cancer who underwent paclitaxel and carboplatin (TC) therapy after eliminating the effect of the target area under the curve (AUC). Risk factors for CBDCA bone marrow toxicity were also identified. A total of 110 patients with primary gynecological cancer or gynecological cancer of unknown primary origin who underwent TC therapy with a target AUC of 5-6 were included herein. Patients with a BMI of ≥25 and <25 kg/m2 were assigned to the obesity and control groups, respectively, and evaluated according to changes in hematological test values (platelet, white blood cell, and hemoglobin counts) starting from initial TC therapy administration until 21 d after the second treatment course. The obesity group had a significantly higher thrombocytopenia rate than the control group. Risk factors for thrombocytopenia ≥ grade 2 included BMI ≥25 kg/m2. Among patients with primary gynecological cancer or gynecological cancer of unknown primary origin who had a BMI of ≥25 kg/m2, those receiving CBDCA may be at increased risk for thrombocytopenia ≥ grade 2 when the dosage is calculated using the Calvert formula with the creatinine clearance level.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Genital Neoplasms, Female/drug therapy , Obesity/complications , Paclitaxel/adverse effects , Thrombocytopenia/chemically induced , Aged , Body Mass Index , Female , Hemoglobins/analysis , Humans , Leukocyte Count , Middle Aged , Obesity/immunology , Platelet Count , Risk Factors , Thrombocytopenia/immunology
3.
Biol Pharm Bull ; 38(5): 740-5, 2015.
Article in English | MEDLINE | ID: mdl-25740003

ABSTRACT

Comparative studies of the potency of long- and short-acting erythropoiesis-stimulating agents (L-ESAs and S-ESAs) on erythropoietic activity in patients with chronic kidney disease without dialysis have not been performed, although L-ESAs are used in many countries. We performed a retrospective analysis of non-dialysis (ND) patients who had received L-ESA or S-ESA. More days were needed for the S-ESA-treated group (368 d) to reach the haemoglobin (Hb) reference range than for the L-ESA-treated group (126 d). Therefore, we investigated risk factors that influence the period until the Hb level reaches the reference range. Patients were classified into two groups by the period until the Hb level was stabilised within the reference range: the short- and long-term group. Two risk factors for delayed Hb stabilisation were identified: age ≥60 years; and administration of an S-ESA for initial treatment. These findings suggest that the Hb level should be carefully monitored during ESA therapy in elderly ND patients, and that the ESA dose should be increased or L-ESA therapy should be utilised to treat renal anaemia.


Subject(s)
Anemia/prevention & control , Erythropoiesis/drug effects , Erythropoietin/blood , Hematinics/therapeutic use , Hemoglobins/metabolism , Renal Insufficiency, Chronic/complications , Age Factors , Aged , Aged, 80 and over , Anemia/blood , Female , Hematinics/pharmacology , Humans , Immunotherapy, Adoptive , Male , Middle Aged , Renal Dialysis , Renal Insufficiency, Chronic/blood , Retrospective Studies , Time Factors
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