Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34.468
Filtrar
3.
World J Surg Oncol ; 19(1): 280, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535176

RESUMO

BACKGROUND: This study was designed to probe into the effect of cisplatin combined with capecitabine on nasopharyngeal carcinoma (NPC). METHODS: A total of 136 NPC patients treated for the first time in our hospital from January 2016 to March 2017 were collected and divided into two groups: A and B. Among them, 66 in group A were treated with cisplatin intravenous drip, while 70 in group B were treated with capecitabine on the basis of group A. The efficacy, toxic and side effects, and quality of life of the two groups were observed. RESULTS: The short-term efficacy of group B was better than that of group A (p<0.05). The toxic and side effects of group B were lower than that of group A (p<0.05). The quality of life in group B was higher than that in group A (p<0.05). CONCLUSIONS: Cisplatin combined with capecitabine-induced chemotherapy for local NPC can improve the quality of life and reduce the toxic and side effects.


Assuntos
Cisplatino , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Quimiorradioterapia , Cisplatino/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Prognóstico , Qualidade de Vida
4.
BMC Gastroenterol ; 21(1): 313, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348673

RESUMO

BACKGROUND: Chemoradiation with capecitabine followed by surgery is standard care for locally advanced rectal cancer (LARC). Severe diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiation therapy. The aim of this study was to describe the risk factors and the impact of body composition on severe diarrhea in patients with LARC during preoperative chemoradiation with capecitabine. METHODS: A single centre retrospective cohort study was conducted in a tertiary referral centre. All patients treated with preoperative chemoradiation with capecitabine for LARC from 2009 to 2015 were included. Patients with locally recurrent rectal cancer who received chemoradiation for the first time were included as well. Logistic regression analyses were performed to identify risk factors for severe diarrhea. RESULTS: A total of 746 patients were included. Median age was 64 years (interquartile range 57-71) and 477 patients (64%) were male. All patients received a radiation dosage of 25 × 2 Gy during a period of five weeks with either concomitant capecitabine administered on radiation days or continuously during radiotherapy. In this cohort 70 patients (9%) developed severe diarrhea. In multivariable logistic regression analyses female sex (OR: 4.42, 95% CI 2.54-7.91) and age ≥ 65 (OR: 3.25, 95% CI 1.85-5.87) were the only risk factors for severe diarrhea. CONCLUSIONS: Female patients and patients aged sixty-five or older had an increased risk of developing severe diarrhea during preoperative chemoradiation therapy with capecitabine. No relation was found between body composition and severe diarrhea.


Assuntos
Fluoruracila , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Composição Corporal , Capecitabina/efeitos adversos , Estudos de Coortes , Desoxicitidina/efeitos adversos , Diarreia/induzido quimicamente , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do Tratamento
6.
Zhonghua Zhong Liu Za Zhi ; 43(8): 883-888, 2021 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-34407596

RESUMO

Objective: To assess the therapeutic efficacy and safety of the gemcitabine combined with nedaplatin (GN) chemotherapy for metastatic human epidermal growth factor receptor-2 (HER-2) negative breast cancer patients. Methods: Forty-five patients with HER-2 negative recurrent metastatic breast cancer who had received prior adjuvant or neoadjuvant therapy with anthracycline and/or taxanes were enrolled. All the patients received GN regime from January 2014 to February 2019. The therapeutic efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST) 1.1. The adverse response was evaluated and monitored according to common terminology criteria for adverse events (CTCAE). The progression-free survival (PFS) and overall survival (OS) and prognostic factors were also analyzed. Results: All of the 45 patients received 4 course GN, 1 of them achieved complete response, 21 achieved partial response. The objective response rate was 48.9 (95% CI: 33.7%-64.1%). Grade 3-4 hematological toxicities include leukopenia occurred in 10 (22.2%) of patients, neutropenia in 13 (28.9%) patients, and thrombocytopenia in 8 (17.6%) patients. The grade 3-4 hematological toxicities mainly manifested as nausea and vomiting, and the incidence was 4.4% (2/45). Among the 45 patients, 34 died, the median PFS was 5.1 (95% CI: 3.9-6.1) months and the median OS was 17.6 (95% CI: 13.1-20.9) months. Conclusion: The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for metastatic breast cancer patients previously treated with anthracyclines and/or taxanes.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Feminino , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia , Compostos Organoplatínicos , Resultado do Tratamento
7.
Trials ; 22(1): 556, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419125

RESUMO

BACKGROUND: Colorectal cancer is a major public concern, being the second deadliest cancer in the world. Whereas survival is high for localized forms, metastatic colorectal cancer has showed poor prognosis, with a 5-year survival barely surpassing 11%. Conventional chemotherapies against this disease proved their efficiency and remain essential in first-line treatment. However, the large number of authorized protocols complexifies treatment decision. In common practice, such decision is made on an empirical basis, by assessing benefits and risks for the patient. In other words, there is currently no efficient means of predicting the efficacy of any chemotherapy protocol for metastatic colorectal cancer. METHODS/DESIGN: The use of a chemosensitivity assay, the Oncogramme®, should help clinicians administer the best chemotherapy regimen to their patients. We hypothesize it would ultimately improve their survival. In this multicentred, prospective trial (ONCOGRAM), eligible patients with metastatic colorectal cancer are randomized to determine whether they will receive an Oncogramme®. For clinicians whose patients benefited from the assay (arm A), results are used as a decision support tool. Patients not undergoing the Oncogramme® procedure are treated according to current practice, without the assistance of the assay (arm B). Primary outcome is 1-year progression-free survival. Secondary outcomes include response rates, as well as 6-month and 1-year survival rates. DISCUSSION: This study aims at investigating the clinical utility of the Oncogramme® as a decision support tool for the treatment of patients with metastatic colorectal cancer. If the Oncogramme® positively influenced patient overall survival and/or progression-free survival, it would be of great value for clinicians to implement this assay within the current landscape of personalized medicine tools, which include genomics and biomarker assays. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03133273 . Registered on April 28, 2017.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
J Int Med Res ; 49(8): 3000605211038135, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34433331

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). METHODS: A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. RESULTS: A total of seven RCTs were included (n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. CONCLUSION: The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.


Assuntos
Mieloma Múltiplo , Neutropenia , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Mieloma Múltiplo/tratamento farmacológico
9.
Trials ; 22(1): 568, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446057

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and multimodal strategies, such as surgery plus neoadjuvant chemotherapy (NAC)/adjuvant chemotherapy, have been attempted to improve survival in patients with localized PDAC. To date, there is one prospective study providing evidence for the superiority of a neoadjuvant strategy over upfront surgery for localized PDAC. However, which NAC regimen is optimal remains unclear. METHODS: A randomized, exploratory trial is performed to examine the clinical benefits of two chemotherapy regimens, gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GA), as NAC for patients with planned PDAC resection. Patients are enrolled after the diagnosis of resectable or borderline resectable PDAC. They are randomly assigned to either NAC regimen. Adjuvant chemotherapy after curative resection is highly recommended for 6 months in both arms. The primary endpoint is tumor progression-free survival time, and secondary endpoints include the rate of curative resection, the completion rate of protocol therapy, the recurrence type, the overall survival time, and safety. The target sample size is set as at least 100. DISCUSSION: This study is the first randomized phase II study comparing GS combination therapy with GA combination therapy as NAC for localized pancreatic cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000021484 . This trial began in April 2016.


Assuntos
Adenocarcinoma , Nanopartículas , Neoplasias Pancreáticas , Paclitaxel Ligado a Albumina/uso terapêutico , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Proteínas de Ligação ao GTP/uso terapêutico , Humanos , Proteínas de Membrana , Terapia Neoadjuvante/efeitos adversos , Paclitaxel , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Prospectivos
10.
In Vivo ; 35(5): 2821-2829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410974

RESUMO

BACKGROUND/AIM: Standard chemotherapy for advanced urothelial carcinoma (UC) patients with moderate renal dysfunction has not yet been established. PATIENTS AND METHODS: We retrospectively assessed outcomes of patients with advanced UC who underwent first-line chemotherapy with full-/reduced-dose gemcitabine plus cisplatin (GC-f/GC-r) or full-/reduced-dose gemcitabine plus carboplatin (G-Car-f/G-Car-r) according to renal function. RESULTS: Seventy-eight patients were included in this study. The objective response rate was 42%, 30%, 42%, and 27% for the GC-f, GC-r, G-Car-f, and G-Car-r groups, respectively. For the GC-r and G-Car-f groups, the median progression-free survival and the median overall survival was 4.5 vs. 7.0 months (p=0.07) and 7.5 months vs. 12.0 months (p=0.124), respectively. Grade 3/4 thrombocytopenia occurred more frequently in the GC-r group than the G-Car-f group (80% vs. 38%, p=0.021). CONCLUSION: G-Car-f could be more beneficial than GC-r for patients with advanced UC who have moderate renal dysfunction.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/efeitos adversos , Humanos , Rim/fisiologia , Platina , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico
11.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361790

RESUMO

Cancer occurrence is rapidly increasing all over the world, including in developing countries. The current trend in cancer management requires the use of herbal remedies since the majority of anticancer drugs are known to be costly, with unwanted side effects. In the Eastern Cape province, the use of medicinal plants for cancer management has been climbing steadily over the past two decades due to their cultural belief, low cost, efficacy, and safety claims. With the aim of identifying some potential anticancer plants for probable drug development, this study was undertaken to review plants reported by ethnobotanical surveys in the Eastern Cape province of South Africa for the traditional management of cancer. Information regarding plants used for cancer management in the Eastern Cape province was obtained from multidisciplinary databases and ethnobotanical books. About 24 plant species belonging to twenty families have been reported to be used for the traditional management of cancer in the Eastern Cape province. Among the anticancer plant species, only 16 species have been explored scientifically for their anticancer activities. This review authenticated the use of anticancer plant species in the Eastern Cape province and, therefore, identified several promising unexplored species for further scientific evaluation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Etnobotânica/métodos , Etnofarmacologia/métodos , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/epidemiologia , Neoplasias/patologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Fitoterapia/métodos , Extratos Vegetais/química , Plantas Medicinais , África do Sul/epidemiologia , Inquéritos e Questionários
12.
Gan To Kagaku Ryoho ; 48(8): 1037-1042, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34404072

RESUMO

BACKGROUND: Cisplatin that is used in the treatment of gastric cancer not only has gastrointestinal side effects but also has a high serum protein-bound fraction. Reduction of serum albumin concentration may cause increase the risk of cisplatin- induced neutropenia. Hence, alteration of serum albumin concentration poses a major safety issue during anticancer therapy. METHODS: For gastric cancer patients who received cisplatin plus S-1 therapy, we investigated the relationship between the serum albumin concentration before cisplatin administration in the treatment course during which the neutrophil count reached nadir and the neutrophil count fluctuation after cisplatin administration. RESULTS: In the grade 3-4 neutropenia and grade 0-2 neutropenia groups, the mean serum albumin concentration before cisplatin administration was 3.39±0.60 and 3.85±0.59 g/dL, respectively; in the former group were significantly lower than in the latter group(p=0.006). Lower serum albumin concentrations before cisplatin administration were significantly correlated with a decrease in neutrophil count after cisplatin administration(r=0.463, p<0.001). According to the receiver operating characteristic curve analysis, patients with serum albumin concentrations below 3.25 g/dL before cisplatin administration exhibited a significantly higher incidence of grade 3-4 neutropenia(odds ratio: 4.33). CONCLUSIONS: Decreased serum albumin levels were found to be strongly associated with the prediction of the development of severe neutropenia. Our findings emphasize serum albumin concentration needs to be evaluated before each administration of cisplatin.


Assuntos
Neutropenia , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Humanos , Neutropenia/induzido quimicamente , Estudos Retrospectivos , Albumina Sérica , Neoplasias Gástricas/tratamento farmacológico
13.
Nat Commun ; 12(1): 4803, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376657

RESUMO

Chemotherapies may increase mutagenesis of healthy cells and change the selective pressures in tissues, thus influencing their evolution. However, their contributions to the mutation burden and clonal expansions of healthy somatic tissues are not clear. Here, exploiting the mutational footprint of some chemotherapies, we explore their influence on the evolution of hematopoietic cells. Cells of Acute Myeloid Leukemia (AML) secondary to treatment with platinum-based drugs show the mutational footprint of these drugs, indicating that non-malignant blood cells receive chemotherapy mutations. No trace of the 5-fluorouracil (5FU) mutational signature is found in AMLs secondary to exposure to 5FU, suggesting that cells establishing the leukemia could be quiescent during treatment. Using the platinum-based mutational signature as a barcode, we determine that the clonal expansion originating the secondary AMLs begins after the start of the cytotoxic treatment. Its absence in clonal hematopoiesis cases is consistent with the start of the clonal expansion predating the exposure to platinum-based drugs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hematopoese/efeitos dos fármacos , Leucemia Mieloide/genética , Mutagênese/efeitos dos fármacos , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Evolução Clonal/efeitos dos fármacos , Evolução Clonal/genética , Células Clonais/efeitos dos fármacos , Células Clonais/metabolismo , Células Clonais/patologia , Estudos de Coortes , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Hematopoese/genética , Humanos , Isocitrato Desidrogenase/genética , Leucemia Mieloide/induzido quimicamente , Mutação/efeitos dos fármacos , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/genética , Platina/administração & dosagem , Platina/efeitos adversos , Proteína Supressora de Tumor p53/genética
14.
Hematology ; 26(1): 577-587, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34384339

RESUMO

OBJECTIVES: Compared with the 3 + 7 regimen, the cladribine-containing regimen has led to improvements in the rate of complete remission (CR) in the treatment of newly diagnosed acute myeloid leukemia (AML) patients. We conducted a systematic review and meta-analysis to investigate the overall efficacy and safety of cladribine-containing regimens in the induction treatment of newly diagnosed AML patients. METHODS: Eligible studies were identified from the PubMed, EMBASE, and Cochrane Library databases. Efficacy was assessed by CR rate, disease-free survival (DFS), and overall survival (OS). Safety was evaluated based on the early death (ED) rate, days for neutrophils<0.5 × 109/L, days for platelets<50 × 109/L, and duration of hospital stay after treatment. RESULTS: A total of 14 clinical trials were included in this meta-analysis, enrolling a total of 1058 newly diagnosed AML patients. The pooled estimate with a 95% confidence interval (CI) for CR was 64% (95% CI: 58-70%). Compared with the control group, the CR rate of the cladribine-containing regimen was higher (OR was 1.92 (95% CI: 1.55-2.38)). The combined ED rate was estimated to be 10% (95% CI: 5-14%). Compared with the control group, the ED rate of the cladribine-containing regimen was not increased (OR was 1.09 (95% CI: 0.78-1.53)). CONCLUSION: This meta-analysis suggests that cladribine-containing regimens are likely to be effective and safe for induction treatment of newly diagnosed AML patients. However, large sample size and prospective controlled studies are needed to confirm our findings.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cladribina/efeitos adversos , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/diagnóstico , Resultado do Tratamento
15.
BMJ Case Rep ; 14(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244190

RESUMO

A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 µmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.


Assuntos
Hepatite B , Falência Hepática , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/uso terapêutico , Vírus da Hepatite B , Humanos , Masculino , Rituximab/efeitos adversos , Ativação Viral
16.
Am J Clin Oncol ; 44(9): 487-494, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269694

RESUMO

AIM: Capecitabine (Cape) is routinely used for the neoadjuvant chemoradiation treatment (NACRT) of locally advanced rectal cancers (LARCs). Previous reports have suggested that the concomitant use of proton pump inhibitors (PPIs) may affect the efficacy of Cape, although the true effect of PPIs when used with Cape as a radiosensitizer for neoadjuvant radiation is unclear. The aim of our study was to evaluate the impact of concurrent PPI use along with fluorouracil (FU) and Cape based NACRT in terms of pathologic and oncological outcomes, in patients with LARC. METHODS: LARC patients treated at our center with NACRT from 2010 to 2016 were identified. Postoperative pathology and follow-up outcomes were examined for any differences with relation to the use of PPIs concurrently with FU and Cape based NACRT and adjuvant chemotherapy regimens. RESULTS: Three hundred four and 204 patients received treatment with FU and Cape based NACRT. No difference in pathologic complete response rate was noted between the 2 arms with the concurrent use of PPIs (25.8% and 25%, respectively, P=0.633); or with and without the use of PPIs in the Cape-NACRT arm specifically (20% and 20.7%, P=0.945). At a median follow-up of 5 years, no statistical difference in local or distant control was noted in the Cape-NACRT patients, with and without concomitant PPI use (P=0.411 and 0.264, respectively).Multivariate analysis showed no association of PPI use and NACRT with Cape, in terms of local control (hazard ratio=0.001, P=0.988) or overall survival (hazard ratio=1.179, confidence interval=0.249-5.579, P=0.835). CONCLUSIONS: Our study revealed that there was no adverse pathologic or oncological outcome with the concurrent use of PPIs along with Cape-NACRT in the treatment of LARC. We report that it may be safe to use PPIs if essential, in this clinical setting, although it would be wise to exercise caution.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Inibidores da Bomba de Prótons/uso terapêutico , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Quimiorradioterapia/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
17.
BioDrugs ; 35(4): 417-428, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34264503

RESUMO

BACKGROUND: Bevacizumab is an antiangiogenic recombinant humanized monoclonal antibody that inhibits tumor growth. FKB238, a bevacizumab biosimilar, has analytical pharmacokinetic and safety profiles similar to those of bevacizumab. OBJECTIVE: This phase III trial (NCT02810457) compared the efficacy and safety of FKB238 with that of bevacizumab in patients with advanced/recurrent non-squamous non-small-cell lung cancer (non-sq-NSCLC). METHODS: This global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized patients with advanced/recurrent non-sq-NSCLC to receive intravenous infusions of either FKB238 15 mg/kg or bevacizumab 15 mg/kg. All patients received intravenous infusions of paclitaxel 200 mg/m2 and carboplatin (area under the curve 6.0) immediately prior to investigational products for 4-6 cycles. FKB238 and bevacizumab were administered on day 1 of each 21-day cycle until objective progressive disease by RECIST version 1.1 or other discontinuation criteria were met. The primary efficacy endpoint was overall response rate (ORR), including complete and partial response and based on blinded independent central review assessment. Other efficacy determinations included progression-free survival (PFS), overall survival (OS), and immunogenicity. Adverse events and severity were reported. RESULTS: The ORR for the intent-to-treat (ITT) population (N = 731) was 51.6% in the FKB238 arm (N = 364) and 53.7% in the bevacizumab arm (N = 367). The FKB238:bevacizumab ORR ratio (ITT population) was 0.96 (90% confidence interval [CI] 0.86-1.08), and the difference in ORR (per-protocol set) between FKB238 and bevacizumab was - 0.02 (95% CI - 0.09 to 0.06). Both CIs fell within the prespecified equivalence margins. Estimated median PFS was 7.72 and 7.62 months in the FKB238 and bevacizumab arms, respectively (hazard ratio 0.97; 95% CI 0.82-1.16). Treatment-emergent adverse events (TEAEs) were reported for 94.2% and 95.1% of patients in the FKB238 and bevacizumab arms, respectively. Grade 3 or higher TEAEs were reported for 53.6% and 55.5% of patients in the FKB238 and bevacizumab arms, respectively. Serious TEAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and bevacizumab, respectively. CONCLUSIONS: Efficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC. TRIAL REGISTRATION NUMBER: NCT02810457.


Assuntos
Medicamentos Biossimilares , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Carboplatina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel , Resultado do Tratamento
18.
Cancer Treat Rev ; 99: 102255, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34332292

RESUMO

Poly-(ADP)-ribose polymerase inhibitors (PARPi) are a class of oral anticancer drugs first developed as "synthetically lethal" in cancers harboring BRCA1/BRCA2 inactivating mutations. In high-grade serous or endometrioid ovarian cancers (HGOC), PARPi demonstrated benefit as maintenance therapy in relapsing BRCA-mutated and non-mutated tumors. Recently, they extended their indications to frontline maintenance therapy. This review summarizes the current place of PARPi (i) as maintenance or single agent in recurrent disease and (ii) frontline maintenance with different settings. We reviewed the course of biomarker identification, the challenge of overcoming resistance to PARPi and future combinations with targeted therapies, including anti-angiogenic, immune checkpoint inhibitors and DNA damage response inhibitors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Quimioterapia de Manutenção , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Int J Clin Oncol ; 26(10): 1805-1811, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34236556

RESUMO

BACKGROUND: Addition of cytarabine to high-dose methotrexate (HD-MTX) chemotherapy improves outcome of primary CNS lymphoma (PCNSL); however, the combination therapy increases toxicity. Sequential chemotherapy and cranial radiation may decrease toxicity without altering efficacy. METHODS: This was a single-center, retrospective cohort study of consecutive newly diagnosed immunocompetent PCNSL patients treated with HD-MTX (5 cycles of 3 g/m2 every 2 weeks) followed by consolidation whole-brain radiotherapy (WBRT) and cytarabine (2 cycles of 3 g/m2/d for 2 days every 3 weeks) from January 2013 to December 2020. Initial WBRT before HD-MTX was allowed in patients with significant disability or brain edema at presentation. Primary outcome was progression-free survival (PFS). Key secondary outcomes were response rate, treatment-related toxicity, and overall survival (OS). RESULTS: Of 41 patients, 25 patients had a complete response (CR) and ten patients had a partial response, inferring an overall response rate (ORR) of 85.4% and a CR rate of 60.9%. More than 90% of patients were able to tolerate and complete the HD-MTX. The incidence of ≥ grade 3 hematologic and non-hematologic toxicities were 4.8% and 17.1%, respectively. Treatment-related mortality rate was 2.4%. There was no difference in toxicity between patients with age < 60 and ≥ 60 years. At the median follow-up duration of 39.8 months, the median PFS was 35.2 months (95% CI 12.4-69.3) and median OS was 46.5 months (95% CI 21.8-NR). CONCLUSION: High-dose methotrexate followed by consolidation whole-brain radiotherapy and cytarabine has acceptable efficacy, great tolerability, and low toxicity in newly diagnosed PCNSL patients.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encéfalo , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Estudos de Coortes , Citarabina/efeitos adversos , Humanos , Linfoma/tratamento farmacológico , Linfoma/radioterapia , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
Am J Clin Oncol ; 44(9): 443-448, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34310349

RESUMO

INTRODUCTION: The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, and plays a central role in cell proliferation, growth, differentiation, migration, and survival. Temsirolimus (CCI-779), a selective inhibitor of the mTOR, is an ester analog of rapamycin (sirolimus) with improved aqueous solubility and pharmacokinetic (PK) properties. Preclinical studies have confirmed additive and synergistic antitumor activity in cancer cell lines (breast, prostate cancer) with combinations of taxanes and mTOR inhibitors. We conducted a phase I open-label, dose-escalation study to determine the maximal tolerated dose (MTD) of docetaxel in combination with temsirolimus in patients with refractory solid tumors. PATIENTS AND METHODS: Eligible patients had a diagnosis of a refractory solid malignancy, measurable disease, and adequate organ function. Patients were sequentially enrolled in 4 dose level intravenous combinations of docetaxel and temsirolimus. Temsirolimus was administered weekly with docetaxel administered every 3 weeks. Laboratory data for tumor markers and radiologic imaging were conducted prestudy and then after every 2 cycles of the treatment. Radiologic response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Blood samples for PK and pharmacodynamic analysis were planned to be drawn at MTD. Apart from the traditional 3+3 design, we also implemented Bayesian Optimal Interval design which uses isotonic regression method to select MTD. We proceeded with isotonic regression analysis by using 20% dose-limiting toxicity (DLT) rate as target. RESULTS: Twenty-six patients were treated in this study in 4 cohorts and dose levels. Fourteen males and 12 females were enrolled with a median age of 50 years (range of 27 to 72 y) and median Eastern Cooperative Oncology Group performance score of 1. Tumor histologies included pancreas (6), colon (5), rectum (3), gallbladder (2), non-small cell lung (2), endometrium (1), neuroendocrine (1), esophagus (1), stomach (1), pharynx (1), small intestine (1), and duodenum (1). Stable disease was observed in 2/4 (50%), 3/7 (43%), 4/10 (40%), and 3/5 (60%) patients in cohorts 1, 2, 3, and 4, respectively. Dose escalation in cohorts 2, 3, and 4 was complicated by DLTs such as grade 4 neutropenia and grade 3 diarrhea and an inability for patients to tolerate treatments during and beyond cycle 1 without dose reductions. Therefore, we could not determine an MTD or recommended phase II dose using the traditional 3+3 study analysis. Blood samples for PK and pharmacodynamic analysis were not collected since MTD was not determined. By using 20% DLT rate closest to the target, isotonic regression analysis showed identical estimated DLT rates in dose -1 (docetaxel 50 mg/m2 and temsirolimus 15 mg/m2) and dose level 1 (docetaxel 60mg/m2 and temsirolimus 15 mg/m2). CONCLUSIONS: Dose escalation of docetaxel and temsirolimus was limited by severe myelosuppressive toxicity in this phase I study. Most of the DLTs occurred after cycle 1 of therapy hence, we were unable to determine MTD or collect blood samples for PK and pharmacodynamic analysis. Our trial did not meet its objectives due to significant DLTs with this chemotherapy combination. Although our novel use of Bayesian Optimal Interval design using isotonic regression method to select MTD showed identical estimated DLT rates in dose levels 1 and -1, clinically our patients were not able to complete 2 cycles of this regimen without dose reductions due to myelosuppressive toxicity in either of these dose levels, and hence, escaped clinical validity. This combination regimen should not be studied further at the dose levels and schedules tested in our study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Idoso , Docetaxel/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...