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Background: Venetoclax (VEN) in combination with hypomethylating agent (HMA) therapy is a standard treatment option for patients with newly diagnosed acute myeloid leukemia (AML); however, data are limited in the relapsed or refractory (R/R) populations and in those with poor-risk disease. A retrospective review was conducted involving patients with AML who received HMA alone or in combination with VEN (VEN + HMA). Methods: VEN + HMA was compared to HMA alone in first-line and R/R settings. Patients were stratified by specific HMA and line of therapy. The primary endpoint was overall response rate (ORR) up to 6 months from start of treatment. Results: Fifty-two patients were evaluated for efficacy and 78 patients for safety. ORR was 67% (VEN + HMA) versus 80% (HMA) in the first line and 50% versus 22% in R/R setting. A greater clinical benefit was seen with VEN + HMA compared to HMA in both lines of therapy (first-line: 87% vs. 80%; R/R: 75% vs. 67%). The median duration of response was longer with VEN + HMA first-line, but shorter in the R/R setting compared to HMA (8.3 vs. 7.2 months and 2.5 vs. 3.7 months, respectively). Of the 32 patients who responded to therapy, 63% had a complex karyotype. Survival benefits were greater with VEN + HMA in both lines of therapy, although not statistically significant. Grade 3/4 neutropenia was reported in all patients receiving VEN, and 95% of these patients also experienced grade 3/4 thrombocytopenia. There were three cases of tumor lysis syndrome. Conclusion: The addition of VEN to HMA has consistently shown benefit as first-line treatment and may have some benefit in R/R settings as well. Further studies are needed to compare across various lines of treatment and unfavorable disease. Dynamic strategies that improve toxicity management should be considered.
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Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described. Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642). Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population. Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.
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Cytomegalovirus (CMV) is the most clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that can further increase CMV infection risk. Prophylaxis with letermovir, an oral antiviral approved to prevent CMV, has been shown to decrease the incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation, but there is a lack of data confirming this benefit in patients with GVHD. In this single-center, retrospective study, we assessed the incidence of clinically significant CMV infection (CS-CMVi) in allo-HCT patients who received letermovir prophylaxis (n = 119) and who developed aGVHD compared to a control group (n = 143) who did not receive letermovir. Among aGVHD patients, letermovir prophylaxis decreased CS-CMVi in patients with aGVHD (HR 0.08 [95% CI 0.03-0.27], p < 0.001), reduced non-relapsed mortality (p = 0.04) and improved overall survival (p = 0.04). This data suggests that letermovir prophylaxis improves outcomes by preventing CS-CMVi in patients with aGVHD.
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Chimeric antigen receptor T cell (CAR T) therapy has been integrated into treatment algorithms for acute leukemia, lymphoma, and, most recently, multiple myeloma. The number of clinical trials in both hematologic and solid tumor malignancies for new products and potential indications continues to grow. The clinical toxicities of CAR T therapy include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which often warrant inpatient admission for close monitoring and treatment. Consequently, many centers have built processes around the administration of these cells in the inpatient setting. As new products gain Food and Drug Administration approval with more manageable toxicity profiles, and as institutions gain experience with the management of these toxicities, outpatient administration and monitoring should be expected. In addition, payor reimbursements for inpatient treatment have put the sustainability of inpatient CAR T therapy in jeopardy, especially for centers with a payor mix that includes a high proportion of Medicare patients. This has the serious potential to limit access to care. As the use of CAR T therapy continues to expand, changes in payment models, care settings, or both are needed to ensure the sustainability of safe, efficient, and cost-effective treatment. This review outlines the efficacy and toxicity of currently approved products, as well as best practices to optimize the management of CAR T cell therapy in the outpatient setting.
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Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Anciano , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Medicare , Pacientes Ambulatorios , Resultado del Tratamiento , Estados UnidosRESUMEN
A retrospective cohort study was conducted to assess differences in efficacy and tolerability between a busulfan AUC target of 16.4 mg × Hr/L per day (FluBu4K) and a conventional RIC regimen (FluBu2). Adult patients with a diagnosis of AML or MDS who received fludarabine + busulfan conditioning with or without antithymocyte globulin between 2015 and 2018 were included. The primary outcome was relapse free survival. Overall, 74 patients received conditioning with either FluBu4K or FluBu2. At 18 months, relapse-free survival was not significantly different, at 63.9% with FluBu4k compared to 57.5% with FluBu2 (p = 0.49). There was a statistically significant difference in the cumulative incidence of relapse at 18 months in favor of the FluBu4K regimen, at 12.0% vs 32.5% (p = 0.047). The results of this study indicate that for select patients, there may be benefit in choosing targeted FluBu4K over FluBu2. Adverse effects other than mucositis were not significantly different.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Área Bajo la Curva , Busulfano , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Vidarabina/análogos & derivadosRESUMEN
BACKGROUND: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Recent advances in immunotherapy have resulted in the development of chimeric antigen receptor-modified T-cell (CAR-T) therapy, such as axicabtagene ciloleucel (axi-cel). However, axi-cel administration is not without risks of toxicity. PATIENTS AND METHODS: This retrospective study of 37 patients with relapsed or refractory diffuse large B-cell lymphoma evaluated the incidence and severity of common and severe safety events after axi-cel treatment in a real-world setting. Ninety percent of patients had received 3 or more prior lines of therapy (median prior therapies 3, range 2-7) before receiving CAR-T therapy, and 32.4% had relapsed after prior stem-cell transplantation. RESULTS: All but one patient experienced cytokine release syndrome (CRS) of any grade (97.3%). Of those 36 patients, 83.3% experienced maximum CRS grade of 1 or 2, occurring after a median of 27 hours and persisting for a median of 6 days. Twenty-seven patients (73.0%) experienced neurotoxicity of any grade. Of those 27 patients, 96.3% experienced maximum neurotoxicity grade of 2 or higher, occurring after a median of 145 hours (6 days) and persisting for a median of 7 days. All 10 patients aged 65 or older had neurotoxicity of grade 2 or higher, compared to 59.3% (11/27) under age 65 (P = .02). Patients with baseline Eastern Cooperative Oncology Group performance status score of 2 were significantly more likely to have shorter time to neurotoxicity compared to patients with performance status of 0 (P = .01). CONCLUSION: With more real-life experience and data, we will be able to define and refine management of toxicities unique to CAR-T therapy.
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Antineoplásicos Inmunológicos/efectos adversos , Productos Biológicos/efectos adversos , Síndrome de Liberación de Citoquinas/inducido químicamente , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Enfermedades del Sistema Nervioso/inducido químicamente , Adulto , Anciano , Anemia/inducido químicamente , Femenino , Estado de Salud , Humanos , Inmunoterapia Adoptiva/efectos adversos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Retratamiento , Estudios Retrospectivos , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Adulto JovenRESUMEN
The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplantation (HCT) or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical HCT or cellular therapy pharmacy services using telemedicine capabilities in the inpatient and outpatient settings to maintain an equivalent level of clinical practice while minimizing viral spread in a high-risk, immunocompromised population. In addition, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy recipients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 expand, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT recipients. Attention to drug-drug interactions (DDIs) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc-prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already caused stress on the usual supply chain. Detailed prescribing algorithms, decision pathways, and specific patient population stock may be necessary. The COVID-19 pandemic has challenged all members of the healthcare team, and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations while also remaining committed to providing compassionate and safe care for patients undergoing HCT and cellular therapies.
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Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Manejo de la Enfermedad , Trasplante de Células Madre Hematopoyéticas , Pandemias , Servicio de Farmacia en Hospital/organización & administración , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Betacoronavirus/patogenicidad , COVID-19 , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/genética , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Pacientes Internos , Pacientes Ambulatorios , Seguridad del Paciente , Neumonía Viral/diagnóstico , Neumonía Viral/genética , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Opinión Pública , SARS-CoV-2 , Sociedades Médicas , Telemedicina/métodos , Estados Unidos/epidemiología , Tratamiento Farmacológico de COVID-19 , Sueroterapia para COVID-19RESUMEN
Acute graft-versus-host-disease (aGVHD) is a complication after allogeneic stem cell transplant. After the failure of treatment with high dose corticosteroids, steroid-refractory aGVHD (SR aGVHD) is associated with high rates of mortality. Tocilizumab has evidence of activity in SR aGVHD. For patients ineligible for trials, the OSU James Comprehensive Cancer Center has been utilizing tocilizumab as first-line therapy for SR aGVHD. We retrospectively report on 15 patients who received tocilizumab. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 49 years. Median time to tocilizumab administration was 9 days (range, 3-16). Six patients had complete responses (40%) with a resolution of aGVHD. From the last contact, median overall survival for responders was not yet reached vs. 31 days for non-responders (p = .0002). Patients with skin and/or GI aGVHD demonstrated the greatest benefit. Patients with liver aGVHD did not respond. Future studies are needed to evaluate tocilizumab prior to steroid failure.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Glucocorticoides/farmacología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/administración & dosificación , Enfermedad Aguda/mortalidad , Enfermedad Aguda/terapia , Adulto , Anciano , Aloinjertos/efectos de los fármacos , Aloinjertos/inmunología , Anticuerpos Monoclonales Humanizados/efectos adversos , Progresión de la Enfermedad , Resistencia a Medicamentos , Femenino , Glucocorticoides/uso terapéutico , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Humanos , Inmunosupresores/efectos adversos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto JovenAsunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/terapia , Acondicionamiento Pretrasplante/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Análisis de Supervivencia , Microangiopatías Trombóticas/mortalidad , Acondicionamiento Pretrasplante/métodosRESUMEN
Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.
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Ácido Aminocaproico/efectos adversos , Antifibrinolíticos/efectos adversos , Neoplasias Hematológicas/complicaciones , Hemorragia/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Tromboembolia/epidemiología , Adulto , Anciano , Cateterismo Venoso Central/efectos adversos , Catéteres de Permanencia/efectos adversos , Femenino , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trombocitopenia/etiología , Trombocitopenia/prevención & control , Tromboembolia/inducido químicamente , Resultado del TratamientoRESUMEN
Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.
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Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/análogos & derivados , Enfermedades Renales/inducido químicamente , Enfermedades Renales/epidemiología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Anciano , Anciano de 80 o más Años , Azacitidina/efectos adversos , Estudios de Cohortes , Comorbilidad , Decitabina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The initial dose of bendamustine, an alkylating agent used in treating indolent lymphoma (iNHL) and mantle cell lymphoma, is variable in clinical practice. 134 patients treated with bendamustine and rituximab were evaluated for starting dosage, patient characteristics, toxicities, and clinical outcome. The starting dosage ranged from 50 to 90 mg/m2. Lower starting dosage (<90 mg/m2) was associated with relapsed disease, increased age and worse performance status (PS), histologic subtype other than follicular lymphoma, baseline renal impairment, and cytopenias. No significant difference was observed in toxicities between patients treated with 90 mg/m2 compared with lower doses. The starting dose of 90 mg/m2 was associated with a higher complete response rate (56% vs. 29%) and longer progression free survival (PFS) (39.5 months vs. 19.7 months). However, in a multivariable model, the higher starting dose was not associated with longer PFS in those with similar age, histology, PS, and number of prior therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Rituximab/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Acute graft-versus-host-disease (aGVHD) is a frequent and often lethal complication of allogeneic hematopoietic stem cell transplant despite prophylaxis. Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody that has evidence of activity in patients with steroid refractory (SR) GVHD. We retrospectively report on nine patients with grade 3 or 4 SR aGVHD who received tocilizumab. Eight mg/kg of tocilizumab was administered intravenously every 3-4 weeks. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 48 years. Five patients had alternate donor sources. Median time from aGVHD onset to tocilizumab administration was 44 days. Two patients had complete responses and two had partial responses. Median survival from start of tocilizumab was 26 days (range 13-1054). Our limited experience demonstrated an overall response rate of 44% (CR + PR); however, this response was not durable. Further studies are needed to determine the optimal time for tocilizumab initiation.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Resistencia a Medicamentos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Adulto , Anticuerpos Monoclonales Humanizados/farmacología , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Trasplante de Células Madre Hematopoyéticas , Humanos , Infecciones/diagnóstico , Infecciones/etiología , Masculino , Persona de Mediana Edad , Receptores de Interleucina-6/antagonistas & inhibidores , Esteroides/uso terapéutico , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del TratamientoRESUMEN
The ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo-secretory or non-secretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, lenalidomide and/or bortezomib. We show that although M protein appears to outperform sFLC comparatively over the course of induction therapy, the addition of FLC to M protein further informs the characterization of residual disease status post-induction. Moreover, sFLC at the time of stem cell mobilization appears to hold prognostic power for survival endpoints following high-dose chemotherapy/autologous stem cell transplant (HDC/SCT). These findings suggest potentially novel roles for sFLC in patients with MM with an intact M protein receiving novel agent-based induction strategies followed by HDC/SCT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Drogas en Investigación/administración & dosificación , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Mieloma Múltiple/sangre , Proteínas de Mieloma/análisis , Anciano , Ácidos Borónicos/administración & dosificación , Bortezomib , Terapia Combinada , Dexametasona/administración & dosificación , Monitoreo de Drogas , Femenino , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Humanos , Estimación de Kaplan-Meier , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/cirugía , Neoplasia Residual , Pronóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirazinas/administración & dosificación , Inducción de Remisión , Talidomida/administración & dosificación , Talidomida/análogos & derivadosRESUMEN
OBJECTIVE: To investigate whether the incidence of thromboembolic events (venous and arterial) increases when bevacizumab-based chemotherapy and erythropoietin stimulating agents (ESAs) are used in combination versus alone. METHODS: A retrospective, pilot study of 79 colorectal cancer patients treated with chemotherapy were divided into 3 groups: bevacizumab (n = 28), ESA (n = 21), and bevacizumab plus ESA (n = 28). The primary end point was the incidence of thromboembolic events. Secondary endpoints included median time-to-event; effect of anticoagulation; and association with concurrent chemotherapy, baseline risk factors, hemoglobin, and performance status. RESULTS: The incidence of thromboembolic events was 11% in the bevacizumab group, 23.8% in the ESA group, and 30% in the combination group (P = 0.194). The median time-to-event was 7.5, 3.5, and 2.5 months, respectively (P = 0.060). The 5 month difference in time-to-event between the bevacizumab group and combination group was significant (P = 0.045). When combining all patients, ESA treatment, prior venous thromboembolic event (VTE), obesity, cardiac disease, and use of exogenous hormones were strong predictors for thromboembolic events. Prior VTE was a strong predictor in those patients in the combination group. CONCLUSION: The incidence of thromboembolic events was increased with the combination of bevacizumab plus ESA compared with either agent alone with chemotherapy. Median time-to-event in the combination group was significantly shorter compared with the bevacizumab group. Prior VTE, cardiac disease, obesity, and exogenous hormone use should be taken in consideration when using the combination of bevacizumab and ESAs.