Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 357
Filtrar
1.
Jpn J Clin Oncol ; 50(2): 122-128, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31665356

RESUMO

BACKGROUND: Adjuvant capecitabine and oxaliplatin (CAPOX) is a standard treatment for resected colon cancer; however, in patients with moderate renal impairment, the incidence of CAPOX-related adverse events (AEs) and the rate of early discontinuation are higher than in patients with no or mild renal impairment. The aim of this retrospective study was to assess the impact of baseline renal function on the safety and discontinuation of adjuvant CAPOX therapy started with the standard dose of capecitabine in elderly patients with colon cancer. METHODS: Data from patients aged ≥65 years old who received CAPOX at the standard starting dose as adjuvant therapy for stage II/III colon cancer were collected and analyzed retrospectively. Patients were divided into two groups based on their renal function: CLcr-H (patients with a creatinine clearance [CLcr] ≥50 ml/min) and CLcr-L (CLcr <50 ml/min), and AEs and discontinuations were assessed. RESULTS: Overall, 189 patients were assessed (CLcr-H group = 137 and CLcr-L group = 52). No patients experienced grade 4 AEs. The incidence of grade 3 CAPOX-related AEs was higher in the CLcr-L group (42.3%) than in the CLcr-H group (31.3%). The proportion of patients who discontinued treatment within four cycles due to AEs was also higher in the CLcr-L group (21.1%) than in the CLcr-H group (2.9%). Multivariate analysis identified that CLcr <50 ml/min was the only significant risk factor for CAPOX therapy discontinuation due to AEs (P = 0.0008). CONCLUSIONS: This study demonstrates that the tolerability of adjuvant CAPOX therapy was decreased in elderly patients with impaired renal function. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry number UMIN000016446.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Rim/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias do Colo/sangue , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Creatinina/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Rim/fisiologia , Masculino , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Vigilância de Produtos Comercializados , Estudos Retrospectivos , Fatores de Risco
2.
N Engl J Med ; 382(7): 597-609, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31825569

RESUMO

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/administração & dosagem , Oxazóis/administração & dosagem , Proteínas Tirosina Quinases/antagonistas & inibidores , Piridinas/administração & dosagem , Quinazolinas/administração & dosagem , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/secundário , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Capecitabina/efeitos adversos , Quimioterapia de Consolidação , Diarreia/induzido quimicamente , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Oxazóis/efeitos adversos , Intervalo Livre de Progressão , Piridinas/efeitos adversos , Quinazolinas/efeitos adversos , Receptor ErbB-2/análise , Trastuzumab/efeitos adversos
3.
BMJ Case Rep ; 12(11)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31791985

RESUMO

Chemotherapy-induced diarrhoea (CID) is a risk of antineoplastic regimens, often associated with 5-fluorouracil (5-FU), irinotecan and capecitabine. Current treatment guidelines for CID include the use of loperamide and octreotide but do not account for other therapies, including budesonide. Small case reports have shown benefit with budesonide in CID secondary to 5-FU and irinotecan, but there is no literature base addressing budesonide use in CID secondary to capecitabine. We describe a case of a patient with severe capecitabine-induced diarrhoea that was refractory to guideline based therapy but resolved with the use of budesonide.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Budesonida/uso terapêutico , Capecitabina/efeitos adversos , Diarreia/tratamento farmacológico , Glucocorticoides/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Idoso de 80 Anos ou mais , Diarreia/induzido quimicamente , Feminino , Humanos , Neoplasias Retais/tratamento farmacológico
5.
Eur J Oncol Nurs ; 43: 101670, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586645

RESUMO

PURPOSE: Breast cancer patients who undergo docetaxel-based chemotherapy regimens can have hand-foot syndrome (HFS), which negatively impacts their ability to perform daily activities. The purpose of the study was to assess, in breast cancer patients receiving chemotherapy: the perceived levels of HFS-related symptoms of the feet, hands or fingers; and HFS-related restrictions in daily activities; as well as to identify factors associated with these symptoms and restrictions. METHODS: This cross-sectional study examined breast cancer patients who received docetaxel-based chemotherapy from the general surgery outpatient department and oncology outpatient department of a medical center in northern Taiwan. A set of structured questionnaires were used to measure patients' HFS-related symptoms and HFS-related restrictions in daily activities. RESULTS: Of the 85 breast cancer patients studied, 41.2% reported HFS. Patients had higher level of HFS-related foot symptoms than HFS-related hand or fingers symptoms. Greater restriction in HFS-related daily activities was associated with more HFS-related hand or fingers symptoms and more HFS-related foot symptoms; these factors explained 44.7% of the variance in restriction of activities. CONCLUSION: Skin care and patient education should be provided to manage the HFS of breast cancer patients receiving chemotherapy.


Assuntos
Atividades Cotidianas , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Síndrome Mão-Pé/etiologia , Adulto , Capecitabina/efeitos adversos , Estudos Transversais , Feminino , Síndrome Mão-Pé/fisiopatologia , Síndrome Mão-Pé/psicologia , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Taiwan
6.
J Chemother ; 31(7-8): 424-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516092

RESUMO

In the current report we present the case of a patient experiencing a life-threatening drug-drug interaction involving the concurrent administration of capecitabine and brivudine. A 65- year-old female with metastatic breast cancer was commenced on brivudine for Herpes Zoster, while on capecitabine treatment, by a physician unfamiliar with the potential repercussions of this drug-drug interaction. As a result, she developed skin rash, severe oral mucositis, and severe and prolonged pancytopenia. These side effects were attributed to a serious interaction of capecitabine with brivudine, resulting in inhibition of dihydropyrimidine dehydrogenase. The patient was admitted for supportive care including intravenous hydration, parenteral nutrition, mouth care solutions, fluconazole, antimicrobial therapy, filgrastim, red blood cell and platelet transfusions. She successfully recovered and was discharged on the 26th day after her admission. Drug-drug interactions can be serious, even life-threatening; thus the physicians should be cautious when prescribing new drugs.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antivirais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Bromodesoxiuridina/análogos & derivados , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Idoso , Antivirais/uso terapêutico , Bromodesoxiuridina/efeitos adversos , Bromodesoxiuridina/uso terapêutico , Interações Medicamentosas/fisiologia , Feminino , Herpes Zoster/tratamento farmacológico , Humanos
7.
BMC Cancer ; 19(1): 929, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533662

RESUMO

BACKGROUND: Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer. METHODS: We performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stage II and stage III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: Between August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29-77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of '0' and 14 had scores of '1'. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8-78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7). CONCLUSIONS: Postoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides adequate 3-year DFS prospects. TRIAL REGISTRATION: This clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Oxaliplatina/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/efeitos adversos , Estudos Prospectivos , Neoplasias Retais/cirurgia
8.
Oncol Res Treat ; 42(11): 607-611, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557756

RESUMO

BACKGROUND: Metastatic breast cancer with obstructive jaundice due to para-aortic lymph node enlargement is an unusual case that poses a therapeutic challenge in determining a chemotherapy regimen. CASE REPORT: A 61-year-old woman presented with triple-negative left invasive ductal breast carcinoma with liver and pulmonary metastases. After receiving gemcitabine and carboplatin as the 4th-line treatment, chemotherapy was postponed due to an increased bilirubin level. Abdominal imaging revealed para-aortic lymph node metastases compressing the distal common hepatic duct. The patient then received capecitabine along with ursodeoxycholic acid. This relieved her jaundice after 8 cycles of chemotherapy, and radiologic evaluation revealed a complete resolution of the obstructive jaundice. CONCLUSION: This finding emphasizes the success of capecitabine regimen as a salvage therapy in a metastatic breast cancer patient with hyperbilirubinemia and opens up the possibility of optimizing systemic chemotherapy for metastatic obstructive jaundice in the setting of limited facility resources.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Icterícia Obstrutiva/etiologia , Neoplasias de Mama Triplo Negativas/complicações , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Feminino , Humanos , Icterícia Obstrutiva/diagnóstico , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Radiografia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/diagnóstico
9.
Zhonghua Zhong Liu Za Zhi ; 41(9): 708-711, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550863

RESUMO

Objective: To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods: Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results: The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) µg/ml, without significant difference of (123.09±56.70) µg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05). Conclusion: The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.


Assuntos
Capecitabina/efeitos adversos , Capecitabina/sangue , Neoplasias do Colo/tratamento farmacológico , Omeprazol/efeitos adversos , Omeprazol/sangue , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/uso terapêutico , China/epidemiologia , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Fluoruracila/administração & dosagem , Refluxo Gastroesofágico/induzido quimicamente , Refluxo Gastroesofágico/epidemiologia , Azia/induzido quimicamente , Azia/epidemiologia , Humanos , Omeprazol/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
10.
Cir Cir ; 87(S1): 38-42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31501632

RESUMO

Capecitabine is a prodrug used primarily as a chemotherapeutic agent. Despite its good tolerance, it has several adverse effects, including the appearance of eruptive nevi. We present the case of a patient, with a history of EC IV breast adenocarcinoma and superficial extension melanoma, which developed 2 weeks after the start of therapy with capecitabine multiple eruptive palmoplantar pigmented lesions, with diverse benign dermatoscopic patterns. With the increasing incidence of solid tumors, these agents are being more used. It is important that the treating physician knows its adverse effects and apply non-invasive diagnostic tools like dermoscopy to avoid unnecessary biopsies.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Dermoscopia , Erupção por Droga/diagnóstico por imagem , Dermatoses do Pé/induzido quimicamente , Dermatoses da Mão/induzido quimicamente , Adenocarcinoma , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama , Capecitabina/uso terapêutico , Diagnóstico Diferencial , Erupção por Droga/etiologia , Feminino , Dermatoses do Pé/diagnóstico por imagem , Dermatoses da Mão/diagnóstico por imagem , Humanos , Melanoma/diagnóstico , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Segunda Neoplasia Primária/tratamento farmacológico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico
11.
BMJ Case Rep ; 12(9)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31537598

RESUMO

Capecitabine is an oral fluoropyrimidine used to treat solid tumours such as colorectal and breast cancer. A rare but severe side effect is capecitabine-induced leukoencephalopathy, including bilateral lesion to the corticospinal tract. However, neurological symptoms due to capecitabine treatment are usually reported to be reversible after discontinuation of capecitabine. Here, we present the case of a patient with bilateral degeneration of the corticospinal tract and progressive spastic tetraplegia after chemotherapy with capecitabine mimicking primary lateral sclerosis. Although therapy with capecitabine was ended, symptoms substantially worsened over the following years and the patient finally died from aspiration pneumonia almost 3 years after the application of capecitabine.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Leucoencefalopatias/induzido quimicamente , Tratos Piramidais/efeitos dos fármacos , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/toxicidade , Capecitabina/uso terapêutico , Capecitabina/toxicidade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Diagnóstico Diferencial , Evolução Fatal , Humanos , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico , Pneumonia Aspirativa/etiologia , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Quadriplegia/induzido quimicamente , Quadriplegia/diagnóstico
12.
Farm Hosp ; 43(5): 158-162, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469628

RESUMO

OBJECTIVE: To analyze adverse reactions in patients with nonmetastatic colorectal cancer due to treatment with either innovative  or generic capecitabine and/or to the chemotherapeutic regimen  employed, to the capecitabine alone, or in combination with oxaliplatin  (XELOX). METHOD: Descriptive retrospective study carried out in a secondary level hospital in two study periods (November 2013-April 2014 and  August 2016-May 2017). The collected variables were: exposure  (chemotherapy scheme and/or received medication), control  (demographics, disease and treatment data), and response (adverse  reactions). The statistical analysis of data was performed with the  SPSS® 15.0 program. Results: Fifty patients were included. According to the administered chemotherapeutic scheme, statistically significant  differences were found in the appearance of palmar-plantar  erythrodysesthesia, which is more frequent with monotherapy (p <  0.05), and neurotoxicity, thrombocytopenia and neutropenia, which is  more frequent with XELOX (p < 0.05). Concerning the capecitabine drug  administered, no statistically significant differences were found in  the studied adverse reactions. CONCLUSIONS: The safety profile of two capecitabine formulations - innovative and generic- appears to be associated with the  chemotherapy scheme employed, and not the drug itself. Most palmar- plantar erythrodysesthesia for monotherapy is likely due to the higher  dose of capecitabine used in said scheme. The increase in neurotoxicity,  thrombocytopenia and neutropenia for XELOX is probably due to  cumulative toxicity of two antineoplastic drugs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Relação Dose-Resposta a Droga , Composição de Medicamentos , Medicamentos Genéricos , Feminino , Gastroenteropatias/induzido quimicamente , Síndrome Mão-Pé/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Neutropenia/induzido quimicamente , Oxaliplatina/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente
13.
Cancer Chemother Pharmacol ; 84(4): 819-827, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31388724

RESUMO

OBJECTIVE: Currently, radical surgery with D2 lymphadenectomy has become the standard operation mode of patients in East Asian countries who suffer from resectable gastric cancer. Our target is to compare the efficacy of postoperative adjuvant chemotherapy with S-1 versus SOX/XELOX regimens for gastric cancer after D2 resection. METHODS: We selected 186 patients with gastric cancer who underwent D2 resection in Hangzhou First People's Hospital and Hangzhou Cancer Hospital from June 2014 to June 2017. All patients were followed up for more than 3 years. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS) and toxicity. RESULTS: The 3-year DFS of monotherapy group and combined group were, respectively, 50.7% and 64.0%, while the 3-year OS were, respectively, 62.7% and 71.2%. The 3-year DFS and OS of the combined group were higher than the monotherapy group, but the differences had no statistical significance (3-year DFS: P = 0.071; 3-year OS: P = 0.224). Subgroup analysis showed that the DFS of patients with stage III gastric cancer in monotherapy group was significantly lower than the combined group, with the difference that had statistical significance (P = 0.030), while there was no significant difference in OS (P = 0.186). Most toxic and side effects seen in both groups had no significant differences, while the incidence of hand-foot syndrome and peripheral neurotoxicity in combined group was significantly higher than that in the monotherapy group (P < 0.001). CONCLUSION: For patients with advanced gastric cancer who underwent D2 resection, compared with S-1 regimen, there is prolonged disease-free survival trend with SOX/XELOX regimen, while there is no significant overall survival benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Gastrectomia/métodos , Oxaloacetatos , Ácido Oxônico , Neoplasias Gástricas/tratamento farmacológico , Tegafur , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante/métodos , China/epidemiologia , Estudos de Coortes , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Síndrome Mão-Pé/epidemiologia , Síndrome Mão-Pé/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Oxaloacetatos/administração & dosagem , Oxaloacetatos/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Polineuropatia Paraneoplásica/epidemiologia , Polineuropatia Paraneoplásica/etiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Tegafur/efeitos adversos
14.
Pancreas ; 48(7): 927-930, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31268983

RESUMO

OBJECTIVE: Determine whether a regimen of fixed dose rate gemcitabine plus capecitabine is effective and tolerable for advanced pancreatic adenocarcinoma. METHODS: We performed a retrospective analysis of 62 patients with locally advanced or metastatic pancreatic adenocarcinoma treated at the University of California San Francisco between 2008 and 2016. Treatment was an alternate week schedule of fixed dose rate 1000 mg/m gemcitabine and capecitabine 1000 mg/m (58 patients), 1200 mg/m (12 patients), or 650 mg/m (1 patient) for intended 12 cycles. We evaluated overall survival (OS), progression-free survival (PFS), radiologic response, and adverse events necessitating treatment modification. RESULTS: For metastatic patients, median OS was 10.3 months (95% confidence interval [CI], 6.7-12.1 months), and PFS was 5.6 months (95% CI, 2.6-7.7 months). In locally advanced patients, OS was 12.0 months (95% CI, 4.9-17.1 months), and PFS was 5.4 months (95% CI, 2.5-9.4 months). Radiologic response for metastatic disease (42 patients) was 19% objective response, 45% stable disease, and 36% progressive disease. Treatment required modification for 22 patients due to adverse events, most frequently hand-foot syndrome (18 patients). CONCLUSIONS: Alternate week schedule of fixed dose rate gemcitabine and capecitabine was active and tolerable for advanced pancreatic adenocarcinoma. Overall survival and PFS were comparable to first-line treatments. Importantly, adverse effects appear less severe than first-line treatments.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Síndrome Mão-Pé/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Resultado do Tratamento
15.
Oncology ; 97(4): 211-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266024

RESUMO

OBJECTIVES: The aim of this study was to determine the recommended dose (RD) of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer. METHOD: Patients received irinotecan and oxaliplatin (85 mg/m2) on day 1, and capecitabine (1,000 mg/m2 orally twice daily) on days 1-7 of a biweekly schedule. Three dose levels, ranging from 100 to 150 mg/m2, were explored for irinotecan in sequential cohorts of 6 patients. Dose-limiting toxicities (DLTs) were assessed in the first cycle to determine the RD. RESULTS: Six patients were enrolled. The DLT was grade 3 febrile neutropenia, which was observed in 2 of the 6 patients at dose level 1. The RD of irinotecan was defined as 150 mg/m2. Toxicity was manageable: the most common grade ≥3 toxicities were neutropenia (2 patients), anemia (1 patient), and anorexia (1 patient). Nodal downstaging (cN+ to ypN0) was detected in 2 patients and the T stage was downstaged in 3 patients. CONCLUSIONS: XELOXIRI is a feasible and active regimen for patients with locally advanced rectal cancer. Febrile neutropenia was the DLT, and the RD of irinotecan is 150 mg/m2.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Irinotecano/administração & dosagem , Terapia Neoadjuvante , Oxaliplatina/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Progressão da Doença , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Neoplasias Retais/patologia
16.
Br J Cancer ; 121(4): 332-339, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31312030

RESUMO

BACKGROUND: A phase Ib study of binimetinib and capecitabine for gemcitabine-pretreated biliary tract cancer (BTC) patients was conducted. METHODS: Binimetinib and capecitabine were dosed twice daily on days 1-14, in 3-week cycles. In the dose-escalation (DE) part, three dose levels (DL) were tested (DL1: binimetinib/capecitabine, 15 mg/1000 mg/m2; DL2: 30 mg/1000 mg/m2; DL3: 30 mg/1250 mg/m2). RESULTS: In the DE part, nine patients were recruited and no dose-limiting toxicity was noted. Therefore, the recommended phase 2 dose was determined as DL3. In the expansion part, 25 patients were enrolled. In total, 34 patients, 25 (73.5%) and 9 patients (26.5%) were second-line and third-line settings, respectively. The 3-month progression-free survival (PFS) rate was 64.0%, and the median PFS and overall survival (OS) were 4.1 and 7.8 months. The objective response rate and disease control rate were 20.6% and 76.5%. In total, 68.4% of stable diseases were durable (> 12 weeks). Furthermore, patients with RAS/RAF/MEK/ERK pathway mutations (38.5%) showed significantly better tumour response (p = 0.028), PFS (5.4 vs. 3.5 months, p = 0.010) and OS (10.8 vs. 5.9 months, p = 0.160) than wild type. Most of the adverse events were grade 1/2 and manageable. CONCLUSIONS: A combination of binimetinib and capecitabine shows acceptable tolerability and promising antitumor efficacy for gemcitabine-pretreated BTC, especially in patients with RAS/RAF/MEK/ERK pathway mutations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02773459).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Mutação , Quinases raf/genética , Proteínas ras/genética , Idoso , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/psicologia , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/fisiologia , Qualidade de Vida , Transdução de Sinais , Quinases raf/fisiologia , Proteínas ras/fisiologia
17.
Medicine (Baltimore) ; 98(30): e16667, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348323

RESUMO

BACKGROUND: This study aimed to compare the efficacy and safety of S-1 and capecitabine in patients with metastatic colorectal carcinoma (mCRC). METHODS: Eligible prospective clinical trials were searched and available data were extracted. Odds ratio and hazard ratio of available outcomes including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled for analysis. RESULTS: A total of 6 studies including 828 patients were included. The results of pooled analysis showed no statistical difference in short-term efficacy including ORR (95% confidence interval [CI]: 0.68-1.19; P = .48) or DCR (95% CI: 0.65-1.29; P = .61), or long-term efficacy including PFS (95% CI: 0.75-1.08; P = .26) or OS (95% CI: 0.78-1.13; P = .50). Symptoms of diarrhea at any grade were more prevalent (95% CI: 1.21-2.29; P = .002) in patients treated with S-1, while hand-foot syndrome (HFS) at any grade (95% CI: 0.24-0.48; P < .0001) or high grade (95% CI: 0.09-0.48; P < .0001) was more frequent in capecitabine group. AEs including leucopenia, neutropenia, anemia, thrombocytopenia, vomiting, oral mucositis, stomatitis, elevated alanine transaminase, or peripheral neuropathy showed no statistical difference between S-1 and capecitabine group (all P > .05). CONCLUSIONS: This meta-analysis reveals that S-1 has comparable efficacy, lower risk of HFS and higher incidence of diarrhea compared to capecitabine for treatment in patients with mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Humanos , Metástase Neoplásica , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos
18.
Bull Cancer ; 106(9): 759-775, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31253356

RESUMO

Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Deficiência da Di-Hidropirimidina Desidrogenase/diagnóstico , Deficiência da Di-Hidropirimidina Desidrogenase/tratamento farmacológico , Fluoruracila/efeitos adversos , Pesquisas sobre Serviços de Saúde/estatística & dados numéricos , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biologia , Pesquisa Biomédica , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Neoplasias do Sistema Digestório/tratamento farmacológico , Deficiência da Di-Hidropirimidina Desidrogenase/genética , Feminino , Fluoruracila/uso terapêutico , França , Genótipo , Humanos , Oncologistas , Neoplasias Otorrinolaringológicas/tratamento farmacológico , Farmacovigilância , Guias de Prática Clínica como Assunto , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Mecanismo de Reembolso
19.
Clin Adv Hematol Oncol ; 17(5): 289-298, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31188808

RESUMO

Colon cancer remains a major cause of mortality worldwide. Following adequate surgical resection of lymph node-positive colon cancer, the standard of care since 2004 has been to administer an oxaliplatin-containing regimen (eg, FOLFOX or CAPOX) for 6 months. These regimens have consistently improved oncologic outcomes compared with non-oxaliplatin therapies in multiple adjuvant randomized controlled trials. However, oxaliplatin-induced cumulative dose-dependent neurotoxicity is a major cause of morbidity that can persist years after treatment. The IDEA collaboration is a study that pooled data from 6 concurrent phase 3 trials comparing 3 vs 6 months of adjuvant FOLFOX or CAPOX to evaluate whether a shorter duration of therapy could maintain efficacy while reducing neurotoxicity. In this article, we review the history of adjuvant therapy in stage III colon cancer and comprehensively detail the results of the IDEA collaboration. A risk-based approach focusing on efficacy, toxicity, and patient selection is emphasized to guide discussions regarding the optimal duration of adjuvant therapy in stage III colon cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Esquema de Medicação , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fidelidade a Diretrizes , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Levamisol/administração & dosagem , Levamisol/efeitos adversos , Metanálise como Assunto , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Guias de Prática Clínica como Assunto , Prognóstico , Estudos Prospectivos , Risco , Resultado do Tratamento
20.
Med Sci Monit ; 25: 4831-4836, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31254462

RESUMO

BACKGROUND Colorectal cancer (CRC) is considered to be a worldwide health problem because of its increasing incidence and prevalence. Surgery offers an opportunity for cure, but the postoperative recurrence rate is still high despite the advancement of chemotherapy. This study aimed to assess the efficacy and safety of prolonged capecitabine chemotherapy following CAPOX chemotherapy for stage III  CRC after radical surgery. MATERIAL AND METHODS This study included 212 patients with stage III CRC undergoing open radical surgery from July 2010 to June 2015. Among those patients, 104 patients received prolonged capecitabine chemotherapy (prolonged group) following 8 cycles of CAPOX regimen chemotherapy, while the other 108 patients (control group) received no prolonged chemotherapy. The prolonged chemotherapy consisted of capecitabine (1000 mg/m² per day for 2 weeks) and was repeated every 3 weeks for 8 cycles at most. Long-term survival and toxicities were retrospectively compared. RESULTS Patient characteristics did not differ between the 2 groups. For all patients, no significant difference was found in the 3-year disease-free survival (DFS) (P=0.7775) or 3-year overall survival (OS) rates between the 2 groups (P=0.5787). The prolonged group had significantly higher frequency of hand-foot syndrome (P=0.0267) and paresthesia (P=0.0164). In further subgroup analyses, no benefit for 3-year DFS or 3-year OS of prolonged capecitabine chemotherapy was found in colon cancer or rectal cancer. CONCLUSIONS Prolonged capecitabine chemotherapy following CAPOX regimen chemotherapy failed to improve the survival of patients with stage III CRC after radical surgery.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA