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1.
Anticancer Res ; 41(4): 1937-1944, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813399

RESUMEN

BACKGROUND/AIM: To assess the prognostic relevance of volume-based parameters [whole body (wb)-metabolic tumor volume (MTV) and wb-total lesion glycolysis (TLG)] of pretreatment PET/CT in patients with potentially platinum-responsive recurrent ovarian cancer. PATIENTS AND METHODS: This retrospective investigation analyzed 67 patients at first relapse. RESULTS: At univariate analysis, post-relapse survival and overall survival correlated with residual disease after primary surgery (RD) (p=0.015 and 0.049, respectively), time to recurrence (p=0.005 and p=0.0003), number of recurrence sites (p=0.001 and p=0.0005), treatment at recurrence (p=0.044 and 0.043) and wb-MTV (p=0.023 and 0.021) but not with wb-TLG. RD, time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic variables for post-relapse survival, and time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic factors for overall survival. CONCLUSION: Volume-based parameters of PET/CT are not independent predictors of clinical outcome in potentially platinum-responsive recurrent ovarian cancer.


Asunto(s)
Carcinoma Epitelial de Ovario/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Ováricas/diagnóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carga Tumoral/fisiología , Adulto , Anciano , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Fluorodesoxiglucosa F18 , Humanos , Italia , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Compuestos de Platino/uso terapéutico , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacos
2.
Anticancer Res ; 41(4): 2045-2051, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813412

RESUMEN

BACKGROUND/AIM: To retrospectively evaluate the efficacy and safety of modified TPEx (docetaxel 60 mg/m2 on day 1, cisplatin 60 mg/m2 on day 1, and weekly cetuximab 250 mg/m2 with loading dose of 400 mg/m2) followed by maintenance cetuximab as first-line treatment for inoperable recurrent and/or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We analyzed 22 Japanese patients receiving modified TPEx every 21 days for four cycles with or without prophylactic granulocyte colony-stimulating factor (G-CSF). RESULTS: The best overall response rate was 55% [95% confidence interval (CI)=35-73]. The median progression-free survival and overall survival were 8.9 months (95%CI=3.9-10.2) and 14.3 months (95%CI=10.1-28.2), respectively. Without prophylactic G-CSF, Grade 3/4 neutropenia and febrile neutropenia was common (94% versus 20%; p=0.003 and 41% versus 0%; p=0.11, respectively). CONCLUSION: The modified TPEx is effective, while prophylactic G-CSF is essential.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Cetuximab/administración & dosificación , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cetuximab/efectos adversos , Cisplatino/efectos adversos , Docetaxel/efectos adversos , Esquema de Medicación , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Resultado del Tratamiento
3.
N Engl J Med ; 384(16): 1529-1541, 2021 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-33882206

RESUMEN

BACKGROUND: Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker. METHODS: In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases. RESULTS: A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment. CONCLUSIONS: Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Moléculas de Adhesión Celular/antagonistas & inhibidores , Inmunoconjugados/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Antígenos de Neoplasias , Antineoplásicos/efectos adversos , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Humanos , Inmunoconjugados/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Supervivencia sin Progresión , Análisis de Supervivencia , Neoplasias de la Mama Triple Negativas/mortalidad , Carga Tumoral
4.
Artículo en Inglés | MEDLINE | ID: mdl-33810213

RESUMEN

Ovarian cancer is one of the most common cancers of the reproductive organs. As there are no symptoms in the early stages, it is mainly detected in the advanced stages. Even then, the symptoms are non-specific and include, for example, abdominal pain, early satiety, or changes in bowel habits. Both biochemical marker levels and imaging studies are used in the initial diagnosis. However, it should be emphasized that they are not characterized by high specificity. Treatment is multistage, and usually first-line debulking surgery is used followed by platinum-based chemotherapy. Here we present a clinical case of a 56-year-old female, a carrier of a mutation in the BRCA1 gene, with a history of breast cancer and with recurrent epithelial ovarian cancer. The patient was qualified for treatment with a PARP inhibitor and is currently undergoing treatment with olaparib. In the patient's follow up of 50 months to date, there has been no recurrence of cancer. Few side effects have been observed, and the most serious one that can be effectively treated is anemia. On the basis of the described case, the authors concluded that olaparib treatment is effective, relatively safe, and does not significantly affect daily functioning.


Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Antineoplásicos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Ftalazinas/uso terapéutico , Piperazinas
5.
Lancet Oncol ; 22(4): 450-462, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33794205

RESUMEN

BACKGROUND: Chemoradiotherapy is the standard of care for unresected locally advanced squamous cell carcinoma of the head and neck. We aimed to assess if addition of avelumab (anti-PD-L1) to chemoradiotherapy could improve treatment outcomes for this patient population. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, patients were recruited from 196 hospitals and cancer treatment centres in 22 countries. Patients aged 18 years or older, with histologically confirmed, previously untreated, locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity (unselected for PD-L1 status), an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who could receive chemoradiotherapy were eligible. Patients were randomly assigned (1:1) centrally by means of stratified block randomisation with block size four (stratified by human papillomavirus status, tumour stage, and nodal stage, and done by an interactive response technology system) to receive 10 mg/kg avelumab intravenously every 2 weeks plus chemoradiotherapy (100 mg/m2 cisplatin every 3 weeks plus intensity-modulated radiotherapy with standard fractionation of 70 Gy [35 fractions during 7 weeks]; avelumab group) or placebo plus chemoradiotherapy (placebo group). This was preceded by a single 10 mg/kg avelumab or placebo lead-in dose given 7 days previously and followed by 10 mg/kg avelumab or placebo every 2 weeks maintenance therapy for up to 12 months. The primary endpoint was progression-free survival by investigator assessment per modified Response Evaluation Criteria in Solid Tumors, version 1.1, in all randomly assigned patients. Adverse events were assessed in patients who received at least one dose of avelumab or placebo. This trial is registered with ClinicalTrials.gov, NCT02952586. Enrolment is no longer ongoing, and the trial has been discontinued. FINDINGS: Between Dec 12, 2016, and Jan 29, 2019, from 907 patients screened, 697 patients were randomly assigned to the avelumab group (n=350) or the placebo group (n=347). Median follow-up for progression-free survival was 14·6 months (IQR 8·5-19·6) in the avelumab group and 14·8 months (11·6-18·8) in the placebo group. Median progression-free survival was not reached (95% CI 16·9 months-not estimable) in the avelumab group and not reached (23·0 months-not estimable) in the placebo group (stratified hazard ratio 1·21 [95% CI 0·93-1·57] favouring the placebo group; one-sided p=0·92). The most common grade 3 or worse treatment-related adverse events were neutropenia (57 [16%] of 348 patients in the avelumab group vs 52 [15%] of 344 patients in the placebo group), mucosal inflammation (50 [14%] vs 45 [13%]), dysphagia (49 [14%] vs 47 [14%]), and anaemia (41 [12%] vs 44 [13%]). Serious treatment-related adverse events occurred in 124 (36%) patients in the avelumab group and in 109 (32%) patients in the placebo group. Treatment-related deaths occurred in two (1%) patients in the avelumab group (due to general disorders and site conditions, and vascular rupture) and one (<1%) in the placebo group (due to acute respiratory failure). INTERPRETATION: The primary objective of prolonging progression-free survival with avelumab plus chemoradiotherapy followed by avelumab maintenance in patients with locally advanced squamous cell carcinoma of the head and neck was not met. These findings may help inform the design of future trials investigating the combination of immune checkpoint inhibitors plus CRT. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Quimioradioterapia , Cisplatino/administración & dosificación , Método Doble Ciego , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Placebos/administración & dosificación , Supervivencia sin Progresión , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Nivel de Atención
6.
Gan To Kagaku Ryoho ; 48(3): 375-378, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790161

RESUMEN

Ovarian clear cell carcinoma(OCCC)shows a poor response to standard chemotherapy, and it is often difficult to choose a regimen for patients with recurrent OCCC. Several reports have suggested a synergistic effect between gemcitabine and cisplatin; another report suggested that gemcitabine, platinum, and bevacizumab are efficacious against recurrent ovarian cancer. We treated patients with OCCC using a combination chemotherapy regimen consisting of gemcitabine(1,000 mg/ m2)and cisplatin(40 mg/m2)on days 1 and 15, and bevacizumab(15 mg/kg)on day 1, with the cycle repeated every 4 weeks. Six patients received this therapy after informed consent, and 2 evaluable patients showed a partial response. Adverse events were mild, with Grade 3 anemia, leukopenia, and neutropenia occurring in 67%, 33%, and 17% of cases, respectively. No Grade 4 events were observed, including hematological or non-hematological toxicities. This suggests that a regimen of combined gemcitabine, platinum, and bevacizumab can be efficacious and feasible for the treatment of OCCC.


Asunto(s)
Cisplatino , Neoplasias Ováricas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/uso terapéutico , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico
7.
Gan To Kagaku Ryoho ; 48(3): 419-421, 2021 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-33790174

RESUMEN

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Trifluridina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Combinación de Medicamentos , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pirrolidinas , Timina , Trifluridina/uso terapéutico , Uracilo/uso terapéutico
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 326-333, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33829710

RESUMEN

Objective: To explore the best treatment plan of intravesical instillation for patients with non-muscular invasive bladder cancer (NMIBC), to explore recurrence-related clinicopathological factors after intravesical instillation, and to evaluate the value of the prognosis and prediction models currently used for NMIBC patients. Methods: Starting from 2016, patients who underwent transurethral resection of bladder tumor (TURBT) in our hospital and who received post-surgery diagnosis of having intermediate or high risks for NMIBC were enrolled in the study. They were randomly assigned to different group sat a ratio of 2∶2∶1 for receiving intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) for 19 times, BCG for 15 times, and epirubicin (EPI) for 18 times. The clinicopathological data of the patients were recorded before, during and after instillation therapy, and survival curves were drawn to evaluate the effects of the three regimens, using recurrence-free survival as the endpoint. Clinicopathological data were analyzed to study the associations between various factors and post-instillation recurrence. The consistency index (c-index) was used to evaluate the predictive accuracy of the scoring model of the Spanish Urological Club for Oncological Treatment (CUETO) and the risk tables of European Organization for Research and Treatment of Cancer (EORTC). Results: A total of 93 NMIBC patients (35 in the 19-time BCG group, 37 in the 15-time BCG group, and 21 in the EPI group) were included, with a median follow-up time of 33.46 months. Twenty-two patients experienced tumor recurrence and eight, tumor progression. The survival curve showed that the BCG group had better recurrence-free survival than the EPI group ( P=0.002), while the difference in recurrence-free survival between 19-time BCG and 15-time BCG groups was not statistically significant. Higher general complication rate was seen in the BCG groups compared with the EPI group (84.7% vs. 61.9%, P=0.022), but there was no grade 3-5 adverse events in any group. The c-index of CUETO scoring model and EORTC risk tables was higher than that of the prediction based solely on T stage, nuclear grade, or EAU risk stratification. In addition, the c-index in the BCG group was higher than that in the whole cohort. Conclusion: Among the subjects of this study, the recurrence rate of bladder cancer in the intravesical BCG instillation groups was lower than that of the epirubicin group. EORTC risk tables and CUETO scoring model exhibited higher predictive accuracies in BCG-treated patients than its performance for the whole NMIBC cohort.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Adyuvantes Inmunológicos/uso terapéutico , Administración Intravesical , Vacuna BCG/uso terapéutico , Humanos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
9.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33669072

RESUMEN

Endometrial cancer is one of the most frequently diagnosed gynecological malignancies worldwide. However, its prognosis in advanced stages is poor, and there are only few available treatment options when it recurs. Epigenetic changes in gene function, such as DNA methylation, histone modification, and non-coding RNA, have been studied for the last two decades. Epigenetic dysregulation is often reported in the development and progression of various cancers. Recently, epigenetic changes in endometrial cancer have also been discussed. In this review, we give the main points of the role of DNA methylation and histone modification in endometrial cancer, the diagnostic tools to determine these modifications, and inhibitors targeting epigenetic regulators that are currently in preclinical studies and clinical trials.


Asunto(s)
Neoplasias Endometriales/metabolismo , Histonas/metabolismo , Metilación/efectos de los fármacos , Recurrencia Local de Neoplasia/metabolismo , ARN no Traducido/metabolismo , Acetilación , Secuenciación de Inmunoprecipitación de Cromatina , Metilación de ADN/efectos de los fármacos , Progresión de la Enfermedad , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Epigénesis Genética/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , ARN no Traducido/genética
10.
Lancet Oncol ; 22(3): e105-e118, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33662288

RESUMEN

This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.


Asunto(s)
Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Guías de Práctica Clínica como Asunto/normas , Terapia Recuperativa , Humanos , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/patología
11.
BMC Med Inform Decis Mak ; 21(1): 83, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33663487

RESUMEN

BACKGROUND: Tumor necrosis factor α inhibitors (TNFi) is effective for rheumatoid arthritis (RA) patients who fail to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Because of high cost, the discontinuation is common but often lead to disease relapse. The study aims to investigate, if the combination therapy of csDMARDs is more effective in reducing disease relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi and MTX. METHODS: It will be a two-stage trial. In the first stage, all RA patients who failed to csDMARDs treatment [disease activity score 28 (DAS28)-CRP > 3.2] will receive MTX plus TNFi for no more than 12 weeks. Patients achieving DAS28-CRP < 3.2 during the first stage will be randomized into three groups at 1:1:1 ratio: (A) add hydroxychloroquine (HCQ) and sulfasalazine (SSZ) for the first 12 weeks and then remove TNFi but continue other treatments for the next 48 weeks; (B) maintain TNFi + MTX for 60 weeks; and (C) maintain TNFi + MTX for the first 12 weeks and then remove TNFi but continue MTX monotherapy for the next 48 weeks. The primary outcome will be disease relapse (DAS28-CRP increases by at least 0.6 and > 3.2). Secondary outcomes will include the incremental cost per reducing 1 case of relapse; patient reported intolerance to the treatment; adverse events; change of mean disease activity measured by DAS28, clinical disease activity index (CDAI) and simplified disease activity index (SDAI); the proportion of modified Sharp score increase < 0.3; ultrasound-detected remission in hands; Health Assessment Questionnaire Disability Index (HAQ-DI) and health related quality of life [the five-level EuroQol-5D (EQ-5D-5L) and short form-6D (SF-6D)]. DISCUSSION: The aim of this trail will be to seek effective treatment options of preventing relapse of RA. The results of the current study may provide an instructive recommendation for more economical application of TNFi treatment in RA. Trial registration NCT, NCT02320630. Registered on 16 December 2014. https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2 .


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Análisis Costo-Beneficio , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapéutico , Metotrexato/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Sulfasalazina/uso terapéutico , Resultado del Tratamiento
12.
Cochrane Database Syst Rev ; 3: CD013348, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33661538

RESUMEN

BACKGROUND: Cervical cancer ranks as the fourth leading cause of death from cancer in women. Historically, women with metastatic or recurrent cervical cancer have had limited treatment options. New anti-angiogenesis therapies, such as vascular endothelial growth factor (VEGF) targeting agents, offer an alternative strategy to conventional chemotherapy; they act by inhibiting the growth of new blood vessels, thereby restricting tumour growth by blocking the blood supply. OBJECTIVES: To assess the benefits and harms of VEGF targeting agents in the management of persistent, recurrent, or metastatic cervical cancer. SEARCH METHODS: We performed searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, online registers of clinical trials, and abstracts of scientific meetings up until 27 May 2020. SELECTION CRITERIA: We examined randomised controlled trials (RCTs) that evaluated the use of VEGF targeting agents alone or in combination with conventional chemotherapy or other VEGF targeting agents. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the results of search strategies, extracted data, assessed risk of bias, and analysed data according to the standard methods expected by Cochrane. The certainty of evidence was assessed via the GRADE approach. MAIN RESULTS: A total of 1634 records were identified. From these, we identified four studies with a total of 808 participants for inclusion. We also identified two studies that were awaiting classification and nine ongoing studies. Bevacizumab plus chemotherapy versus chemotherapy Treatment with bevacizumab plus chemotherapy may result in lower risk of death compared to chemotherapy alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.62 to 0.95; 1 study, 452 participants; low-certainty evidence). However, there are probably more specific adverse events when compared to chemotherapy alone, including gastrointestinal perforations or fistulae (risk ratio (RR) 18.00, 95% CI 2.42 to 133.67; 1 study, 440 participants; moderate-certainty evidence); serious thromboembolic events (RR 4.5, 95% CI 1.55 to 13.08; 1 study, 440 participants; moderate-certainty evidence); and hypertension (RR 13.75, 95% CI 5.07 to 37.29; 1 study, 440 participants; moderate-certainty evidence). There may also be a higher incidence of serious haemorrhage (RR 5.00, 95% CI 1.11 to 22.56; 1 study, 440 participants; low-certainty evidence). In addition, the incidence of serious adverse events is probably higher (RR 1.44, 95% CI 1.16 to 1.79; 1 study, 439 participants; moderate-certainty evidence). The incremental cost-effectiveness ratio was USD 295,164 per quality-adjusted life-year (1 study, 452 participants; low-certainty evidence). Cediranib plus chemotherapy versus chemotherapy Treatment with cediranib plus chemotherapy may or may not result in similar risk of death when compared to chemotherapy alone (HR 0.94, 95% CI 0.53 to 1.65; 1 study, 69 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 3.27, 95% CI 0.14 to 77.57; 1 study, 67 participants; very low-certainty evidence); serious haemorrhage (RR 5.45, 95% CI 0.27 to 109.49; 1 study, 67 participants; very low-certainty evidence); serious thromboembolic events (RR 3.41, 95% CI 0.14 to 80.59; 1 study, 60 participants; very low-certainty evidence); and serious hypertension (RR 0.36, 95% CI 0.02 to 8.62; 1 study, 67 participants; very low-certainty evidence). In addition, there may or may not be a similar incidence of serious adverse events compared to chemotherapy alone (RR 1.15, 95% CI 0.75 to 1.78; 1 study, 67 participants; low-certainty evidence). Apatinib plus chemotherapy or chemotherapy/brachytherapy versus chemotherapy or chemotherapy/brachytherapy Treatment with apatinib plus chemotherapy or chemotherapy/brachytherapy may or may not result in similar risk of death compared to chemotherapy alone or chemotherapy/brachytherapy alone (HR 0.90, 95% CI 0.51 to 1.60; 1 study, 52 participants; low-certainty evidence). However, hypertension events may occur at a higher incidence as compared to chemotherapy alone or chemotherapy/brachytherapy alone (RR 5.14, 95% CI 1.28 to 20.73; 1 study, 52 participants; low-certainty evidence). Pazopanib plus lapatinib versus lapatinib Treatment with pazopanib plus lapatinib may result in higher risk of death compared to lapatinib alone (HR 2.71, 95% CI 1.16 to 6.31; 1 study, 117 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 2.00, 95% CI 0.19 to 21.59; 1 study, 152 participants; very low-certainty evidence); haemorrhage (RR 2.00, 95% CI 0.72 to 5.58; 1 study, 152 participants; very low-certainty evidence); and thromboembolic events (RR 3.00, 95% CI 0.12 to 72.50; 1 study, 152 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 12.00, 95% CI 2.94 to 49.01; 1 study, 152 participants; moderate-certainty evidence). There may or may not be a similar incidence of serious adverse events as compared to lapatinib alone (RR 1.45, 95% CI 0.94 to 2.26; 1 study, 152 participants; low-certainty evidence). Pazopanib versus lapatinib Treatment with pazopanib may or may not result in similar risk of death as compared to lapatinib (HR 0.96, 95% CI 0.67 to 1.38; 1 study, 152 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 1.03, 95% CI 0.07 to 16.12; 1 study, 150 participants; very low-certainty evidence); haemorrhage (RR 1.03, 95% CI 0.31 to 3.40; 1 study, 150 participants; very low-certainty evidence); and thromboembolic events (RR 3.08, 95% CI 0.13 to 74.42; 1 study, 150 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 11.81, 95% CI 2.89 to 48.33; 1 study, 150 participants; moderate-certainty evidence). The risk of serious adverse events may or may not be similar as compared to lapatinib (RR 1.31, 95% CI 0.83 to 2.07; 1 study, 150 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: We found low-certainty evidence in favour of the use of bevacizumab plus chemotherapy. However, bevacizumab probably increases specific adverse events (gastrointestinal perforations or fistulae, thromboembolic events, hypertension) and serious adverse events. We found low-certainty evidence that does not support the use of cediranib plus chemotherapy, apatinib plus chemotherapy, apatinib plus chemotherapy/brachytherapy, or pazopanib monotherapy. We found low-certainty evidence suggesting that pazopanib plus lapatinib worsens outcomes. The VEGF inhibitors apatinib and pazopanib may increase the probability of hypertension events.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Antineoplásicos/efectos adversos , Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Sesgo , Braquiterapia/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Intervalos de Confianza , Femenino , Fístula Gástrica/inducido químicamente , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Hipertensión/inducido químicamente , Fístula Intestinal/inducido químicamente , Perforación Intestinal/inducido químicamente , Lapatinib/efectos adversos , Lapatinib/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/irrigación sanguínea , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , Piridinas/efectos adversos , Piridinas/uso terapéutico , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Calidad de Vida , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Tromboembolia/inducido químicamente , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/mortalidad , Adulto Joven
13.
Lancet Oncol ; 22(4): 463-475, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33684370

RESUMEN

BACKGROUND: Results from a phase 2 trial of the TPEx chemotherapy regimen (docetaxel-platinum-cetuximab) showed promising results, with a median overall survival of 14·0 months in first-line recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). We therefore aimed to compare the efficacy and safety of the TPEx regimen with the standard of care EXTREME regimen (platinum-fluorouracil-cetuximab) in this setting. METHODS: This was a multicentre, open-label, randomised, phase 2 trial, done in 68 centres (cancer centres, university and general hospitals, and private clinics) in France, Spain, and Germany. Eligible patients were aged 18-70 years with histologically confirmed recurrent or metastatic HNSCC unsuitable for curative treatment; had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1; and had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less. Participants were randomly assigned (1:1) using the TenAlea website by investigators or delegated clinical research associates to the TPEx regimen or the EXTREME regimen, with minimisation by ECOG performance status, type of disease evolution, previous cetuximab treatment, and country. The TPEx regimen consisted of docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both intravenously on day 1, and cetuximab on days 1, 8, and 15 (intravenously 400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently). Four cycles were repeated every 21 days with systematic granulocyte colony-stimulating factor (G-CSF) support at each cycle. In case of disease control after four cycles, intravenous cetuximab 500 mg/m2 was continued every 2 weeks as maintenance therapy until progression or unacceptable toxicity. The EXTREME regimen consisted of fluorouracil 4000 mg/m2 on day 1-4, cisplatin 100 mg/m2 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on day 1 of cycle 1 and 250 mg/m2 weekly subsequently) all delivered intravenously. Six cycles were delivered every 21 days followed by weekly 250 mg/m2 cetuximab as maintenance therapy in case of disease control. G-CSF support was not mandatory per the protocol in the EXTREME regimen. The primary endpoint was overall survival in the intention-to-treat population; safety was analysed in all patients who received at least one dose of chemotherapy or cetuximab. Enrolment is closed and this is the final analysis. This study is registered at ClinicalTrials.gov, NCT02268695. FINDINGS: Between Oct 10, 2014, and Nov 29, 2017, 541 patients were enrolled and randomly assigned to the two treatment regimens (271 to TPEx, 270 to EXTREME). Two patients in the TPEx group had major deviations in consent forms and were not included in the final analysis. Median follow-up was 34·4 months (IQR 26·6-44·8) in the TPEx group and 30·2 months (25·5-45·3) in the EXTREME group. At data cutoff, 209 patients had died in the TPEx group and 218 had died in the EXTREME group. Overall survival did not differ significantly between the groups (median 14·5 months [95% CI 12·5-15·7] in the TPEx group and 13·4 months [12·2-15·4] in the EXTREME group; hazard ratio 0·89 [95% CI 0·74-1·08]; p=0·23). 214 (81%) of 263 patients in the TPEx group versus 246 (93%) of 265 patients in the EXTREME group had grade 3 or worse adverse events during chemotherapy (p<0·0001). In the TPEx group, 118 (45%) of 263 patients had at least one serious adverse event versus 143 (54%) of 265 patients in the EXTREME group. 16 patients in the TPEx group and 21 in the EXTREME group died in association with adverse events, including seven patients in each group who had fatal infections (including febrile neutropenia). Eight deaths in the TPEx group and 11 deaths in the EXTREME group were assessed as treatment related, most frequently sepsis or septic shock (four in each treatment group). INTERPRETATION: Although the trial did not meet its primary endpoint, with no significant improvement in overall survival with TPEx versus EXTREME, the TPEx regimen had a favourable safety profile. The TPEx regimen could provide an alternative to standard of care with the EXTREME regimen in the first-line treatment of patients with recurrent or metastatic HNSCC, especially for those who might not be good candidates for up-front pembrolizumab treatment. FUNDING: Merck Santé and Chugai Pharma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cetuximab/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Francia/epidemiología , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Platino (Metal)/administración & dosificación , España/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
14.
Lancet Oncol ; 22(4): 512-524, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33721562

RESUMEN

BACKGROUND: PD-1 blockade via pembrolizumab monotherapy has shown antitumour activity and toxicity in patients with relapsed or refractory classical Hodgkin lymphoma. Here, we present interim analyses from the KEYNOTE-204 study evaluating pembrolizumab versus brentuximab vedotin for relapsed or refractory classical Hodgkin lymphoma. METHODS: In this randomised, open-label, phase 3 study, patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma with measurable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 who were ineligible for or had relapsed after autologous haematopoietic stem-cell transplantation (HSCT) were enrolled at 78 hospitals and cancer centres in 20 countries and territories. Patients were randomly assigned (1:1) with an interactive voice response system to pembrolizumab 200 mg intravenously every 3 weeks or brentuximab vedotin 1·8 mg/kg intravenously every 3 weeks. Randomisation was stratified by previous autologous HSCT and status after front-line therapy. Results from the second interim analysis are presented here, with a database cutoff of Jan 16, 2020. The dual primary endpoints assessed in the intention-to-treat population were progression-free survival as assessed by blinded independent central review, and overall survival (not analysed at this interim analysis). Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT02684292. Recruitment for this trial is closed. FINDINGS: Between July 8, 2016, and July 13, 2018, 151 patients were randomly assigned to pembrolizumab and 153 to brentuximab vedotin. After a median time from randomisation to data cutoff of 25·7 months (IQR 23·4-33·0), median progression-free survival was 13·2 months (95% CI 10·9-19·4) for pembrolizumab versus 8·3 months (5·7-8·8) for brentuximab vedotin (hazard ratio 0·65 [95% CI 0·48-0·88]; p=0·0027). The most common grade 3-5 treatment-related adverse events were pneumonitis (six [4%] of 148 patients in the pembrolizumab group vs one [1%] of 152 patients in the brentuximab vedotin group), neutropenia (three [2%] vs 11 [7%]), decreased neutrophil count (one [1%] vs seven [5%]), and peripheral neuropathy (one [1%] vs five [3%]). Serious treatment-related adverse events occurred in 24 (16%) of 148 patients receiving pembrolizumab and 16 (11%) of 152 patients receiving brentuximab vedotin. One treatment-related death due to pneumonia occurred in the pembrolizumab group. INTERPRETATION: Pembrolizumab showed statistically significant and clinically meaningful improvement in progression-free survival compared with brentuximab vedotin, with safety consistent with previous reports. These data support pembrolizumab as the preferred treatment option for patients with relapsed or refractory classical Hodgkin lymphoma who have relapsed post-autologous HSCT or are ineligible for autologous HSCT. FUNDING: Merck Sharp & Dohme Corp (a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA).


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Brentuximab Vedotina/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Brentuximab Vedotina/efectos adversos , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad de Hodgkin/patología , Humanos , Inmunoconjugados/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Adulto Joven
15.
Medicine (Baltimore) ; 100(10): e24824, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725836

RESUMEN

INTRODUCTION: There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors. PATIENT CONCERNS: A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010. DIAGNOSIS: positron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014. INTERVENTIONS: The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg. OUTCOMES: PET-CT imaging showed his lesions obtained remission after 8 months post-treatment. CONCLUSION: Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.


Asunto(s)
Aminopiridinas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Nasales/tratamiento farmacológico , Terapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/inmunología , Inducción de Remisión , Resultado del Tratamiento
16.
J Surg Oncol ; 123(5): 1263-1273, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33524184

RESUMEN

BACKGROUND: The association between the imaging response (structural or metabolic) to neoadjuvant chemotherapy (neoCT) before colorectal liver metastasis (CRLM) and survival is unclear. METHOD: A total of 201 patients underwent their first CRLM resection. A total of 94 (47%) patients were treated with neoCT. A multivariable, Cox proportional hazard regression analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between response groups. RESULTS: Multivariable regression analysis of the CT/MRI (n = 94) group showed no difference in survival (OS and PFS) in patients who had stable disease/partial response (SD/PR) or complete response (CR) versus patients who had progressive disease (PD) (OS: HR, 0.36 (95% CI: 0.11-1.19) p = .094, HR, 0.78 (95% CI: 0.13-4.50) p = .780, respectively), (PFS: HR, 0.70 (95% CI: 0.36-1.35) p = .284, HR, 0.51 (0.18-1.45) p = .203, respectively). In the FDG-PET group (n = 60) there was no difference in the hazard of death for patients with SD/PR or CR versus patients with PD for OS or PFS except for the PFS in the small CR subgroup (OS: HR, 0.75 (95% CI: 0.11-4.88) p = .759, HR, 1.21 (95% CI: 0.15-9.43) p = .857), (PFS: HR, 0.34% (95% CI: 0.09-1.22), p = .097, HR, 0.17 (95% CI: 0.04-0.62) p = .008, respectively). CONCLUSION: There was no convincing evidence of association between imaging response to neoCT and survival following CRLM resection.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/mortalidad , Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/mortalidad , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Tomografía de Emisión de Positrones/métodos , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
17.
Ann Oncol ; 32(5): 631-641, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33539946

RESUMEN

BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/efectos adversos , Supervivencia sin Progresión , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico
18.
BMC Cancer ; 21(1): 189, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33622272

RESUMEN

INTRODUCTION: The present study aims to evaluate the efficacy and safety of apatinib monotherapy or combination therapy for patients with advanced or recurrent biliary tract cancer (BTC). METHODS: Twenty-eight patients with advanced or recurrent BTC who progressed after prior systemic therapies and treated with apatinib from January 2017 to June 2019 were enrolled in this retrospective and observational study. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. RESULTS: A total of 28 patients with advanced or recurrent BTC who progressed after prior systemic therapies received apatinib monotherapy or combination therapy (with capecitabine, S-1, oxaliplatin, irinotecan or PD-1 inhibitor), including 9 cases of gallbladder cancer and 19 cases of cholangiocarcinoma. Six patients achieved PR, 15 patients had SD and 7 patients had PD. Median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95%CI = 1.8-6.8) and 6.2 months (95% CI = 4.6-7.8) respectively. The ORR and DCR were 21.4% (6/28) and 75.0% (21/28), respectively. Most of the adverse events were grade 1-2 in severity, apatinib treatment was well tolerated. CONCLUSIONS: Apatinib monotherapy or combination therapy can improve PFS in patients with advanced or recurrent BTC who progressed after prior systemic therapies, and adverse reactions can be well tolerated. Our study support apatinib therapy as a feasible therapeutic strategy in advanced or recurrent BTC.


Asunto(s)
Neoplasias del Sistema Biliar/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Piridinas/uso terapéutico , Adulto , Anciano , Neoplasias del Sistema Biliar/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piridinas/efectos adversos , Estudios Retrospectivos
19.
Medicine (Baltimore) ; 100(4): e24339, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530227

RESUMEN

BACKGROUND: In recent years, a number of clinical trials for antibody drugs targeting programmed cell death protein 1 (PD1)/programmed cell death 1 ligand 1 (PD-L1) have been carried out on recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN) and reported promising prospects. To further evaluate and understand the effects and risk of anti-PD1/PD-L1 monotherapy vs standard of care (SoC) in R/M SCCHN, we conducted this meta-analysis of published randomized controlled trials. METHOD: The potential eligible trials were searched from Cochrane library and Pubmed and Embase databases. Randomized controlled trials evaluating the effects and risk of anti-PD1/PD-L1 monotherapy vs SoC in platinum refractory R/M SCCHN were selected. The outcomes, including objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse events, were extracted and pooled. RESULTS: 1345 patients with R/M SCCHN from three randomized controlled trials were enrolled in this analysis. Compared with SoC, anti-PD1/PD-L1 monotherapy could provide statistically significant overall survival benefit, hazard ratio (95% confidence interval ) = 0.79 [0.70-0.90]. However, we observed no significant difference between 2 treatments in progression-free survival (hazard ratio [95% confidence interval] = 0.96 [0.85-1.09]). Furthermore, anti-PD1/PD-L1 monotherapy caused less treatment-related adverse events than standard of care. CONCLUSION: Anti-PD1/PD-L1 monotherapy could indeed reduce the risk of death in R/M SCCHN patients, and provide higher safety vs SoC. Expression level of PD-L1 may be a useful biomarker for selecting patients with better response to anti-PD1/PD-L1 monotherapy.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Nivel de Atención/estadística & datos numéricos , Adulto , Antígeno B7-H1/inmunología , Biomarcadores de Tumor/inmunología , Femenino , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/mortalidad , Selección de Paciente , Receptor de Muerte Celular Programada 1/inmunología , Ensayos Clínicos Controlados Aleatorios como Asunto , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Resultado del Tratamiento
20.
Gan To Kagaku Ryoho ; 48(2): 215-218, 2021 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-33597362

RESUMEN

A male patient in his 70s underwent a right lobectomy because of a hepatocellular carcinoma(HCC)located in the right lobe(S6)of his liver. Eleven months after surgery, contrast-enhanced CT showed multiple masses in the residual liver, which were diagnosed as HCC recurrence. He was then treated with hepatic arterial infusion chemotherapy(HAIC). Ten months after the recurrence, the liver tumors progressed. Therefore, treatment was switched to sorafenib(400 mg/day orally)and HAIC(low-dose FP: 5-FU 250 mg plus CDDP 5 mg 5 days/week 4 weeks)sequential therapy. The patient received 2 cycles of sorafenib-HAIC sequential therapy for 11 months, and his liver tumors shrunk considerably. Unfortunately, 24 months after the recurrence of HCC, he died of respiratory failure. The cause of his death was officially determined to be primary lung cancer. An autopsy revealed that most tissues were necrotic, and only a small number of viable tumor cells were present in the liver tumors. This suggests that sorafenib-HAIC sequential therapy was significantly effective in targeting the multiple HCCs in this case.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sorafenib/uso terapéutico , Resultado del Tratamiento
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