RESUMEN

BACKGROUND: F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). METHODS: This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. RESULTS: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 - 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. CONCLUSIONS: A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Factor Estimulante de Colonias de Granulocitos , Neutropenia , Humanos , Femenino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Filgrastim/administración & dosificación , Filgrastim/efectos adversos , Filgrastim/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Epirrubicina/efectos adversos , Epirrubicina/administración & dosificación , Esquema de Medicación

RESUMEN

PURPOSE: We aimed at identifying prevalence, clinical outcomes and prognostic factors in cancer patients with intravenous chemotherapy-induced severe neutropenia (ICISN). METHODS: In this multicenter retrospective cohort study on the clinical data warehouse of Greater Paris University Hospitals (AP-HP), we included all adult patients with solid cancer hospitalized between 2016 and 2021 with intravenous chemotherapy within 30 days prior to severe neutropenia (D70 or D611 ICD-10 codes AND a neutrophil count < 500/mm3). The primary endpoint was referral to intensive care unit (ICU) or death within 30 days. We collected cancer, patient, and treatment characteristics. RESULTS: Among 141,586 cancer inpatients, 40,660 received chemotherapy among whom 661 (1.6%) had ICISN. Median age was 63 years (interquartile range (IQR), 54-70) and 330 patients (49%) were female. The median Charlson score was 10 (IQR, 8-11). Main primary cancers were lung (n = 204, 31%) and breast (n = 87, 13%). Advanced cancers were found in 551 patients (83%), 331 (50%) were in 1st line of chemotherapy, 284 (42%) in the 1st cycle of the current line and 149 (22%) had primary G-CSF. Documented bacterial (mostly gram-negative bacilli) and fungal infections were observed in 113 (17%) and 19 (3%) patients; 58 (9%) were transferred to ICU and 82 (12%) died within 30 days, 372 (56%) patients received subsequent chemotherapy. Independent prognostic factors were the level of monocyte, lymphocyte counts or albuminemia and a documented bacterial infection, while Charlson index and primary prophylactic G-CSF were not associated with patient clinical outcomes. CONCLUSION: Despite the use of primary G-CSF, ICISN remains a frequent event, which leads to ICU death in one on five cases Some prognostic factors of severity have been highlighted and could help clinicians to prevent severe complications.

Asunto(s)

Antineoplásicos , Neoplasias , Neutropenia , Humanos , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Masculino , Anciano , Neoplasias/tratamiento farmacológico , Prevalencia , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Estudios de Cohortes , Pronóstico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Administración Intravenosa

Asunto(s)

Antipsicóticos , Clozapina , Factor Estimulante de Colonias de Granulocitos , Neutropenia , Humanos , Clozapina/efectos adversos , Clozapina/administración & dosificación , Neutropenia/inducido químicamente , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Antipsicóticos/efectos adversos , Antipsicóticos/administración & dosificación , Masculino , Persona de Mediana Edad , Femenino

RESUMEN

BACKGROUND: Trilaciclib, in comparison to placebo plus carboplatin, etoposide, ± atezolizumab (PEA), has shown significant reductions in incidence of severe neutropenia (SN) among patients with extensive-stage small cell lung cancer (ES-SCLC). Despite these findings, real-world utility remains limited. METHODS: A single-center quasi-experimental study compared trilaciclib + PEA (PEAT) versus PEA in ES-SCLC patients. The study period ranged from April 1, 2021 to July 31, 2022, for the PEAT recipients and February 1, 2020, to February 28, 2021, for PEA recipients. The primary endpoint evaluated was incidence of SN after cycle 1 and during the treatment period. Secondary endpoints included measures related to myelopreservation and patient outcomes. RESULTS: Among 34 PEAT and 44 PEA patients, baseline characteristics were similar, except for a higher median age (69 vs 64 years) and more males (64.7% vs 38.6%) in the PEAT cohort. The PEAT cohort exhibited a lower SN rate (3%) versus the PEA cohort (18%), with statistical significance demonstrated on multivariate analysis (p = 0.015). Additionally, the PEAT cohort also demonstrated significant reductions in red blood cell transfusion requirements (3% vs 23%; p = 0.02), grade 3-4 anemia (6% vs 25%; p = 0.03), and grade 3-4 thrombocytopenia (0% vs 11%, p = 0.045). CONCLUSION: Trilaciclib, in combination with PEA, demonstrated an improvement in the safety profile without compromising survival outcomes in ES-SCLC patients. These findings underscore the potential benefits of incorporating trilaciclib in real-world clinical settings for enhanced patient care.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Estadificación de Neoplasias , Pirimidinas , Pirroles

RESUMEN

Polatuzumab vedotin(Pola)combination therapy is used for diffuse large B-cell lymphoma(DLBCL)treatment. In clinical trials, more than 90% of the patients have received granulocyte-colony stimulating factor(G-CSF)as primary prophylaxis. However, reports investigating the benefit of prophylactic administration are lacking. In this study, we addressed the incidence of febrile neutropenia(FN)with and without primary prophylaxis with G-CSF combined with Pola therapy. We observed that the incidence of FN with Pola-BR therapy was 0% and 9.5% with and without G-CSF, respectively. The incidence of FN with Pola-R-CHP tended to be higher: 0% and 31.2% with and without G-CSF, respectively. The duration of hospitalization significantly decreased in the Pola-BR group with G-CSF(11 days vs. 18 days in the group without G-CSF), suggesting that prophylaxis might contribute to this reduction. Although not statistically significant, prophylactic G-CSF administration tended to reduce the incidence of Grade 3 or higher leukopenia and neutropenia, suggesting that primary prophylactic G-CSF administration in Pola combination therapy could contribute to reduced hematologic toxicity.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Filgrastim , Polietilenglicoles , Humanos , Filgrastim/administración & dosificación , Filgrastim/uso terapéutico , Polietilenglicoles/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Adulto , Anciano de 80 o más Años , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Inmunoconjugados

RESUMEN

BACKGROUND: Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD: Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION: In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Neoplasias Gastrointestinales , Neutropenia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Neoplasias Gastrointestinales/tratamiento farmacológico , Neutropenia/prevención & control , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Adulto , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Irinotecán/uso terapéutico , Irinotecán/efectos adversos , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico , China/epidemiología

RESUMEN

The clinical usage of docetaxel (DTX) is severely hindered by the dose-limiting neutropenia and peripheral neurotoxicity of polysorbate 80-solubilized DTX injection, and there are no alternative formulations until now. In this study, we developed a new liposomal formulation of DTX to reduce its toxicities, accompanying with the greatly improved antitumor activity. The DTX was encapsulated into liposomes in the form of hydrophilic glutathione (GSH)-conjugated prodrugs using a click drug loading method, which achieved a high encapsulation efficiency (∼95 %) and loading capacity (∼30 % wt). The resulting liposomal DTX-GSH provided a sustained and efficient DTX release (∼50 % within 48 h) in plasma, resulting in a greatly improved antitumor activities as compared with that of polysorbate 80-solubilized DTX injection in the subcutaneous and orthotopic 4T1 breast tumor bearing mice. Even large tumors > 500 mm3 could be effectively inhibited and shrunk after the administration of liposomal DTX-GSH. More importantly, the liposomal DTX-GSH significantly decreased the neutropenia and peripheral neurotoxicity as compared with that of polysorbate 80-solubilized DTX injection at the equivalent dose. These data suggested that the liposomal DTX-GSH might become a superior alternative formulation to the commercial DTX injection.

Asunto(s)

Antineoplásicos , Docetaxel , Glutatión , Liposomas , Ratones Endogámicos BALB C , Docetaxel/administración & dosificación , Docetaxel/farmacocinética , Docetaxel/farmacología , Docetaxel/química , Animales , Ratones , Glutatión/química , Femenino , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Profármacos/administración & dosificación , Profármacos/química , Profármacos/farmacología , Taxoides/administración & dosificación , Taxoides/farmacología , Taxoides/farmacocinética , Taxoides/química , Polisorbatos/química , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico

RESUMEN

BACKGROUND: Concern about clozapine-associated neutropenia contributes to clozapine's underutilization and racial disparities in access. People with African ancestry are more likely to have lower normative absolute neutrophil counts (ANC), associated with the Duffy null genetic polymorphism. Recent data on clozapine-associated neutropenia in the US are lacking. METHODS: Patients prescribed clozapine in the Johns Hopkins Medicine electronic medical record (EMR) between 2013 and 2023 were identified. Duffy null Associated Neutrophil Count (DANC) was assigned if there were two ANC's < 2000 cells/µL, >30 days apart, before starting clozapine. Rates of neutropenia, timing of first neutropenia, and demographic differences were explored. RESULTS: 974 received clozapine and had ANC's available, with 63.9 % male, 51.1 % White, and 39 % Black. 287 were presumed to start clozapine during the study period, and were 62.4 % male, 46 % White, and 44.9 % Black. No patients developed severe neutropenia. 59 (6.1 %) developed mild or moderate neutropenia. 19 (6.6 %) new starts had presumed DANC, and none developed neutropenia. 11 of 16 presumed new starts who developed neutropenia did so within eight months. No demographic differences were found between groups for presumed new starts. For non-new starts, where DANC assignment was not possible, Black patients were more likely than White patients to develop neutropenia (OR 3.48, 95 % CI [1.65, 7.73]). DISCUSSION: To our knowledge, this is the first observational study of clozapine-associated neutropenia in the US in the past decade, and it includes a substantial proportion of Black patients. ANC monitoring requirements may be too strict, contributing to clozapine underutilization.

Asunto(s)

Antipsicóticos , Clozapina , Neutropenia , Humanos , Clozapina/efectos adversos , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Masculino , Femenino , Adulto , Antipsicóticos/efectos adversos , Persona de Mediana Edad , Estados Unidos , Negro o Afroamericano , Población Blanca , Factores de Tiempo , Recuento de Leucocitos , Esquizofrenia/tratamiento farmacológico , Adulto Joven , Sistema del Grupo Sanguíneo Duffy/genética , Anciano

Asunto(s)

Acitretina , Ictiosis Lamelar , Queratolíticos , Neutropenia , Humanos , Acitretina/efectos adversos , Acitretina/uso terapéutico , Ictiosis Lamelar/tratamiento farmacológico , Queratolíticos/efectos adversos , Queratolíticos/uso terapéutico , Neutropenia/inducido químicamente , Lactante , Masculino , Femenino

RESUMEN

BACKGROUND: Glutathione S-Transferase (GST) is a family of phase II metabolizing enzymes contribute to detoxification and elimination of variety of endogenous as well as exogenous xenobiotics including chemotherapeutic agents. The comprehensive knowledge on the impact of genetic polymorphisms in GST) enzyme coding gene will help to understand the clinical outcomes in breast cancer patients treated with either Adriamycin or paclitaxel or combination of both. In this study we attempted to assess the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and their association with Adriamycin and Paclitaxel induced toxicity reactions in breast cancer patients. METHODS: Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis. RESULTS: After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy. CONCLUSION: The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Doxorrubicina , Gutatión-S-Transferasa pi , Glutatión Transferasa , Paclitaxel , Polimorfismo Genético , Humanos , Glutatión Transferasa/genética , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Gutatión-S-Transferasa pi/genética , Paclitaxel/efectos adversos , Doxorrubicina/efectos adversos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Pronóstico , Genotipo , Anciano , Estudios de Seguimiento , Neutropenia/inducido químicamente , Neutropenia/genética

RESUMEN

Neutropenia, a common side effect of chemotherapy for ovarian cancer, was observed in a 47-year-old female patient undergoing a six-cycle chemotherapy regimen. She experienced recurrent neutropenia and leukopenia but refused granulocyte colony-stimulating factor (G-CSF) due to severe bone pain and high costs. Moxibustion combined with guasha therapy (MGT) was administered each time neutropenia occurred. The treatment involved guasha therapy on the bladder meridian (BL) and the governor vessel (GV), followed by moxibustion at Zhongwan (CV 12), Guanyuan (CV 4), and Shenzhu (GV 12) points over 2-3 days. This approach led to the recovery of neutrophil and leukocyte counts, enabling the patient to complete six chemotherapy cycles without G-CSF. These findings suggest that MGT may enhance neutrophil and leukocyte counts in patients with chemotherapy-induced myelosuppression, presenting a potential alternative for those intolerant to G-CSF. However, further high-quality research is needed to confirm its efficacy.

Asunto(s)

Moxibustión , Neutropenia , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Neutropenia/terapia , Neutropenia/inducido químicamente , Neoplasias Ováricas/tratamiento farmacológico , Moxibustión/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Leucocitos , Neutrófilos , Terapia Combinada , Recurrencia

RESUMEN

High-dose methotrexate (HD-MTX) is used in the treatment of children with central nervous system (CNS) tumors; however, toxicity information is limited. We characterized toxicities following 102 administrations of HD-MTX (4.6-13.5 g/m2) infused over 4 or 24 h in 38 children with a CNS tumor before 6 years of age (2010-2020). Delayed clearance of methotrexate occurred following 24% of infusions. Common Terminology Criteria for Adverse Events v5 grade 2-3 mucositis was observed in 47% of individuals, Grade 4 neutropenia in 76%, and grade 3-4 thrombocytopenia in 58%. No neurotoxicity was observed. HD-MTX can be safely used with supportive care and monitoring.

Asunto(s)

Antimetabolitos Antineoplásicos , Neoplasias del Sistema Nervioso Central , Metotrexato , Humanos , Metotrexato/efectos adversos , Metotrexato/administración & dosificación , Femenino , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Masculino , Preescolar , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/administración & dosificación , Lactante , Niño , Estudios de Seguimiento , Estudios Retrospectivos , Pronóstico , Mucositis/inducido químicamente , Neutropenia/inducido químicamente

RESUMEN

BACKGROUND: To evaluate the risk of neutropenia during treatment with anti-IL-23 antibodies in patients with psoriasis. METHOD: We conducted an observational study with cohort design using MID-NET® in Japan. We identified patients with psoriasis who were newly prescribed anti-IL-23 antibodies, anti-IL-17-antibodies, adalimumab, or apremilast between January 1, 2009, and March 31, 2021. We estimated the adjusted hazard ratio (aHR) of anti-IL-23 antibodies compared to that of anti-IL-17 antibodies, adalimumab, or apremilast, for the risk of grade 2 (neutrophil count < 1,500/µL) or grade 3 (neutrophil count < 1,000/µL) neutropenia. RESULTS: Overall, 287 patients on anti-IL-23 antibodies, 189 patients on anti-IL-17 antibodies, 293 patients on adalimumab, and 540 patients on apremilast were included. Compared with anti-IL-17 antibodies, the aHR (95% confidence interval (CI)) of anti-IL-23 antibodies was 0.83 (0.27-2.51) for grade 2 and 0.40 (0.02-7.60) for grade 3 neutropenia; that when compared with adalimumab was 0.76 (0.28-2.06) for grade 2 but was not calculated for grade 3 as no cases were found; and that compared with apremilast was 3.88 (0.62-24.48) for grade 2 and 0.43 (0.02-11.63) for grade 3 neutropenia. CONCLUSION: No clear increase in the risk of neutropenia with anti-IL-23 antibodies was observed.

Asunto(s)

Adalimumab , Interleucina-17 , Interleucina-23 , Neutropenia , Psoriasis , Talidomida , Humanos , Adalimumab/efectos adversos , Adalimumab/inmunología , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Femenino , Masculino , Neutropenia/inducido químicamente , Neutropenia/inmunología , Neutropenia/epidemiología , Persona de Mediana Edad , Japón , Adulto , Interleucina-17/antagonistas & inhibidores , Interleucina-17/inmunología , Interleucina-23/antagonistas & inhibidores , Interleucina-23/inmunología , Talidomida/efectos adversos , Talidomida/análogos & derivados , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos

Asunto(s)

Antivirales , Ganciclovir , Neutropenia , Valganciclovir , Humanos , Neutropenia/inducido químicamente , Valganciclovir/uso terapéutico , Antivirales/efectos adversos , Ganciclovir/uso terapéutico , Infecciones por Citomegalovirus/complicaciones , Niño , Factores de Riesgo

RESUMEN

BACKGROUND: Clozapine is known to cause agranulocytosis. Mandatory monitoring schemes are aimed at reducing the risk of agranulocytosis and of the consequences of agranulocytosis. All cases of agranulocytosis occurring in people prescribed clozapine are assumed to be caused by clozapine. METHODS: In a previous study, we examined a cohort of patients listed on our hospital database as having had clozapine-induced agranulocytosis and applied specific criteria to identify those with confirmed clozapine-related, life-threatening agranulocytosis. In this study, we examine the cases not meeting these specific criteria. RESULTS: In the original study, 9 of 23 cases met the criteria for clozapine-induced, life-threatening agranulocytosis. Of the 13 remaining cases for whom data were available, 5 were probably caused by clozapine but were not life-threatening. Three cases were the result of concomitant cancer chemotherapy. Three were anomalous results probably related to measurement error. For the remaining two cases, the cause was not identified. CONCLUSION: Not all cases of agranulocytosis occurring in people taking clozapine are caused by clozapine. The widely used threshold criterion-based diagnosis overestimates the risk of agranulocytosis. True clozapine-related agranulocytosis is best identified by pattern-based criteria: rapid fall in neutrophil counts over around 2 weeks to below 0.5 × 109/L for two consecutive days (unless clozapine is stopped very early or granulocyte colony stimulating factor is given) where other possible causes (benign ethnic neutropenia, cancer chemotherapy) can be ruled out.

Asunto(s)

Agranulocitosis , Antipsicóticos , Clozapina , Neutropenia , Clozapina/efectos adversos , Humanos , Neutropenia/inducido químicamente , Antipsicóticos/efectos adversos , Agranulocitosis/inducido químicamente , Masculino , Femenino , Adulto , Persona de Mediana Edad

RESUMEN

INTRODUCTION: Myelosuppression, a challenge in cancer treatment, often results in severe complications. Prophylactic granulocyte colony-stimulating factors, particularly pegfilgrastim, mitigate chemotherapy-induced neutropenia. This narrative review evaluates the role of on-body injector (OBI) devices for pegfilgrastim administration. A comprehensive search strategy of PubMed and AI-powered intuitive search tools, complemented by authors' contributions, yielded a body of papers presenting evidence on OBI devices, their effectiveness and safety, the benefits and challenges of OBI versus pre-filled syringe administration, patient preferences for pegfilgrastim administration, and economic considerations. DISCUSSION: OBI devices prove effective and safe, with advantages such as reduced clinic visits and enhanced adherence. Studies highlight cost-efficiency and expanded access, emphasizing the socioeconomic context. Patient and provider preferences underscore the potential of OBI devices in cancer care, with implications for healthcare resource utilization and pharmacoeconomics. CONCLUSION: The value proposition of OBI devices lies in improving patient outcomes, convenience, resource optimization, and enhancing the overall cancer care experience. As biosimilar OBIs enter the market, they may offer cost savings, further influencing their adoption and their positioning as a cost-efficient alternative in cancer care. Ongoing research and technological advancements are expected to contribute to the broader acceptance of OBI devices in cancer care delivery.

Asunto(s)

Filgrastim , Neutropenia , Polietilenglicoles , Humanos , Filgrastim/uso terapéutico , Filgrastim/administración & dosificación , Polietilenglicoles/administración & dosificación , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación

RESUMEN

AIMS: We studied the pharmacokinetics and exposure-response relationships of the brentuximab vedotin (BV) antibody-drug conjugate (ADC) and unconjugated monomethyl auristatin E in haematologic malignancies. METHODS: This population pharmacokinetic analysis included data from five adult and three paediatric studies. Exposures in virtual adult and paediatric populations following BV 1.8 mg/kg (maximum 180 mg) intravenously every 3 weeks were simulated. Clinical endpoints included overall response rate, grade ≥2 peripheral neuropathy (PN) and grade ≥3 neutropenia. RESULTS: BV ADC exhibited linear pharmacokinetics, well-described by a three-compartment model, with body weight being the only significant covariate for exposure. Monomethyl auristatin E exhibited time-varying formation rate. Simulated steady-state BV ADC exposures in patients aged 12 to <18 years were similar to those of adult patients, but 23%-38% lower in patients aged 2 to <12 years. Despite lower exposure, clinical activity was observed with BV 1.8 mg/kg every 3 weeks in those aged 2 to <12 years (overall response rate: 2 to <12 years, 60%; 12 to <18 years, 43%). In adult, but not paediatric patients, increased BV ADC exposures were associated with grade ≥2 PN and grade ≥3 neutropenia occurrence. CONCLUSIONS: BV pharmacokinetics in adult and paediatric patients were consistent. BV ADC exposures were lower in patients aged 2 to <12 years vs. ≥12 years, but no apparent clinically relevant differences in efficacy, grade ≥2 PN or grade ≥3 neutropenia were observed. These data support body weight-based dosing of BV in patients irrespective of age; thus, dose adjustment in those 2 to <12 years does not appear warranted.

Asunto(s)

Peso Corporal , Brentuximab Vedotina , Inmunoconjugados , Humanos , Niño , Brentuximab Vedotina/administración & dosificación , Brentuximab Vedotina/farmacocinética , Brentuximab Vedotina/efectos adversos , Adolescente , Preescolar , Inmunoconjugados/farmacocinética , Inmunoconjugados/administración & dosificación , Inmunoconjugados/efectos adversos , Masculino , Femenino , Adulto , Modelos Biológicos , Neoplasias Hematológicas/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Adulto Joven , Factores de Edad , Neutropenia/inducido químicamente , Oligopéptidos/farmacocinética , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Persona de Mediana Edad , Anciano , Simulación por Computador

Asunto(s)

Desoxicitidina , Gemcitabina , Neutropenia , Trombocitopenia , Pez Cebra , Pez Cebra/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Animales , Trombocitopenia/inducido químicamente , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico

RESUMEN

Aim: There is limited data available regarding the comparison of Sacituzumab govitecan (SG) vs. chemotherapy in metastatic breast cancer patients.Materials & methods: We performed a systematic review and meta-analysis aimed to assess the safety profile of SG vs. chemotherapy for metastatic breast cancer (mBC) clinical trials.Results: The pooled odds ratio for outcomes such as grade 3-4 and all grade neutropenia, leukopenia, anemia and other non-hematological adverse events showed a higher risk for patients receiving SG. No statistically significant differences were reported in terms of grade 3-4 fatigue, all grade nausea, febrile neutropenia and treatment discontinuation due to adverse events.Conclusion: Our data, coupled with a statistically and clinically meaningful survival benefit, support the use of SG for mBC.

---

[Box: see text].

Asunto(s)

Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Camptotecina , Femenino , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/efectos adversos , Camptotecina/administración & dosificación , Inmunoconjugados , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Resultado del Tratamiento

RESUMEN

OBJECTIVES: This paper critiques the haematological monitoring guidelines for clozapine. It describes the history of clozapine, as well as the pathophysiology and epidemiology of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA). The paper appraises the extant literature on mandatory clozapine haematological monitoring. CONCLUSION: Contemporary Australian protocols for clozapine haematological monitoring are not consistent with the current evidence base. CIN and CIA are rare occurrences, and the associated risk of death is low. Potential modifications to existing guidelines include changing neutrophil thresholds for patients with benign ethnic neutropenia and reducing the frequency or removing haematological monitoring after two years of clozapine treatment.

Asunto(s)

Agranulocitosis , Antipsicóticos , Clozapina , Monitoreo de Drogas , Neutropenia , Clozapina/efectos adversos , Clozapina/sangre , Humanos , Antipsicóticos/efectos adversos , Agranulocitosis/inducido químicamente , Neutropenia/inducido químicamente , Monitoreo de Drogas/métodos , Australia , Guías de Práctica Clínica como Asunto