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1.
Eur J Cancer ; 190: 112941, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37482012

RESUMEN

AIM: ImmunoCobiVem investigated whether a planned switch to atezolizumab after achieving tumour control during run-in with vemurafenib + cobimetinib improves progression-free survival (PFS) and overall survival (OS) compared to continuous targeted therapy (TT) in patients with previously untreated advanced BRAFV600-mutated melanoma. METHODS: In this multicenter phase 2 study, patients received vemurafenib plus cobimetinib. After 3months, patients without progressive disease (PD) were randomly assigned (1:1) to continue vemurafenib + cobimetinib (Arm A) or switch to atezolizumab (Arm B) until first documented PD (PD1). Primary outcome was PFS1 (time from start of run-in until PD1 or death). OS and safety were also assessed. RESULTS: Of 185 patients enroled between November 2016 and December 2019, 135 were randomly assigned after the run-in period (Arm A, n = 69; Arm B, n = 66). Median PFS1 was significantly longer in Arm A versus Arm B (13.9 versus 5.9months; hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.37-0.84; PStratified=0.001). Median OS was not reached in either arm (HR 1.22; 95%CI, 0.69-2.16; PStratified=0.389); 2-year OS was higher in Arm B versus Arm A (67%; 95%CI, 53-78 versus 58%; 95%CI, 45-70). Grade 3/4 AEs occurred in 55% of patients in Arm A and 64% in Arm B; treatment-related AEs led to discontinuation of any drug in 7% and 9% of patients, respectively. CONCLUSION: In patients with BRAFV600-mutated advanced melanoma who achieve tumour control with TT, early switch at 3months to atezolizumab led to rapid loss of tumour control but provided a numerical OS benefit at 2years compared with continued TT.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Vemurafenib , Proteínas Proto-Oncogénicas B-raf/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Melanoma/tratamiento farmacológico , Melanoma/genética , Mutación , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética
2.
Bone Marrow Transplant ; 52(11): 1537-1542, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28805791

RESUMEN

Patients with multiple myeloma (MM) who undergo autologous stem cell transplantation (ASCT) are susceptible to severe infections. Low levels of circulating mannan-binding lectin (MBL) are associated with increased risk of infection. In this prospective study, we evaluated 100 patients who underwent ASCT regarding the effect of MBL on the incidence and severity of febrile episodes. Seventeen patients had MBL levels <500 ng/mL (11 received antibiotic prophylaxis and 6 did not). Although there was no statistical difference regarding the development of febrile episodes between patients with low and normal MBL, among 17 patients with low MBL levels, six out of eleven patients who received antibiotic prophylaxis developed a febrile episode compared with six out of six patients who did not receive antibiotic prophylaxis and developed a febrile episode. Patients with low MBL levels who responded less frequently to first line antibiotic therapy required more frequent administration of a second more advanced line of antibiotics, independently of receiving or not prophylaxis, and required prolonged hospitalization. In the univariate analysis low MBL associated with shorter OS. Our results suggest that patient with low MBL levels should receive antibiotic prophylaxis to reduce the number of febrile episodes and raise the issue of MBL replacement for these patients.


Asunto(s)
Fiebre/sangre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lectina de Unión a Manosa/sangre , Mieloma Múltiple/patología , Adulto , Anciano , Profilaxis Antibiótica/métodos , Femenino , Fiebre/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Estudios Prospectivos , Trasplante Autólogo
3.
Blood Cancer J ; 7(6): e570, 2017 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-28622303

RESUMEN

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.


Asunto(s)
Amiloidosis/tratamiento farmacológico , Bortezomib/uso terapéutico , Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico , Anciano , Amiloidosis/patología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/farmacología , Ciclofosfamida/farmacología , Dexametasona/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
5.
Blood Cancer J ; 6: e428, 2016 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-27232930

RESUMEN

Circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and selectins were prospectively measured in 145 newly-diagnosed patients with symptomatic myeloma (NDMM), 61 patients with asymptomatic/smoldering myeloma (SMM), 47 with monoclonal gammopathy of undetermined significance (MGUS) and 87 multiple myeloma (MM) patients at first relapse who received lenalidomide- or bortezomib-based treatment (RD, n=47; or VD, n=40). Patients with NDMM had increased VCAM-1 and ICAM-1 compared with MGUS and SMM patients. Elevated VCAM-1 correlated with ISS-3 and was independently associated with inferior overall survival (OS) (45 months for patients with VCAM-1 >median vs 75 months, P=0.001). MM patients at first relapse had increased levels of ICAM-1 and L-selectin, even compared with NDMM patients and had increased levels of VCAM-1 compared with MGUS and SMM. Both VD and RD reduced dramatically serum VCAM-1 after four cycles of therapy, but only VD reduced serum ICAM-1, irrespective of response to therapy. The reduction of VCAM-1 was more pronounced after RD than after VD. Our study provides evidence for the prognostic value of VCAM-1 in myeloma patients, suggesting that VCAM-1 could be a suitable target for the development of anti-myeloma therapies. Furthermore, the reduction of VCAM-1 and ICAM-1 by RD and VD supports the inhibitory effect of these drugs on the adhesion of MM cells to stromal cells.


Asunto(s)
Mieloma Múltiple/sangre , Mieloma Múltiple/mortalidad , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Femenino , Humanos , Selectina L/sangre , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Estadificación de Neoplasias , Pronóstico , Recurrencia , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Talidomida/uso terapéutico
6.
Neurogastroenterol Motil ; 22(3): 285-e81, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20028464

RESUMEN

BACKGROUND In diseases defined primarily by the subjective nature of patient self-report, placebo effects can overwhelm the capacity of randomized controlled trials to detect medication-placebo differences. Moreover, it is unclear whether such placebo effects represent genuine psychobiological phenomena or just shifts in selective attention. Knowledge of predictors of the placebo response could improve the design of clinical trials and the delivery of personalized medical care. METHODS In patients with irritable bowel syndrome (IBS), a subset of our previous study that were randomized to placebo treatment (sham acupuncture) or no-treatment group (waitlist), we tested an enriched panel of 10 serum biomarkers at the enrolment and the 3rd week of intervention, using a multiplex electrochemiluminescent immunoassay. KEY RESULTS More pronounced changes overtime in serum levels of osteoprotegerin (OPG) have been found in patients who received placebo treatment compared with the waitlist group (P = 0.039). Moreover, serum levels of OPG at baseline were found to be higher (P = 0.0167) in patients who subsequently achieved adequate relief (AR) of their IBS symptoms, independently of their treatment group. Besides, serum levels of TNF-related weak inducer of apoptosis (TWEAK) at baseline were also higher (P = 0.0144) in patients who reported AR and in particular in those who received the placebo treatment. CONCLUSIONS & INFERENCES These two measurable biological parameters associated with placebo, namely serum OPG and TWEAK, provide a proof of principle for discovering putative molecular signatures of placebo response in IBS and perhaps in other illnesses with patient self-reported outcomes.


Asunto(s)
Síndrome del Colon Irritable/sangre , Osteoprotegerina/sangre , Terapia por Acupuntura , Adulto , Biomarcadores/sangre , Citocina TWEAK , Femenino , Humanos , Síndrome del Colon Irritable/terapia , Masculino , Persona de Mediana Edad , Selección de Paciente , Efecto Placebo , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Resultado del Tratamiento , Factores de Necrosis Tumoral/sangre
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