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2.
Medicine (Baltimore) ; 99(51): e23719, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371122

RESUMO

ABSTRACT: Maintenance treatment after first-line chemotherapy for patients with metastatic colorectal cancer (mCRC) is a priority strategy. However, which medicine is chosen is controversial. This study aimed to determine the efficacy and safety of maintenance treatment with metronomic capecitabine vs observation.In this randomized controlled trial, patients who completed 18 weeks of induction chemotherapy with XELOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy with metronomic chemotherapy or observation until disease progression. The primary endpoint was progression-free survival from randomization; secondary endpoints included overall survival and safety. Analyses were performed by intention to treat.Between January 1st, 2017 and December 31th 2018, 48 patients were enrolled and randomly assigned to receive maintenance treatment with metronomic capecitabine (n = 25) or only observation (n = 23). The median progression-free survival in the metronomic capecitabine group was 5.66 (95% confidence interval [CI] 5.25-6.07) months vs 3.98 (95%CI 3.71-4.24) months in the observation group (hazard ratio 0.11, 95% [CI] 0.04-0.26, P = .000). There was no statistically significant difference in median overall survival: 23.82 (95% CI 22.38-25.25) months in the metronomic capecitabine group vs 21.81 (95% CI 20.23-23.38) months in the observation group (hazard ratio 0.49, 95% CI 0.21-1.11, P = .087). Subgroup analyses were generally consistent with the primary finding. Similar safety profiles were observed in both arms. The most frequent adverse events in metronomic capecitabine group included neutropenia, diarrhea, hand-foot skin reaction, and mucositis.Maintenance therapy with metronomic capecitabine can be considered an alternative option following first-line chemotherapy of XELOX in patients with metastatic colorectal cancer with controlled toxicities.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Oxaloacetatos/uso terapêutico , Administração Metronômica , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oxaloacetatos/administração & dosagem , Oxaloacetatos/efeitos adversos , Intervalo Livre de Progressão
3.
Medicine (Baltimore) ; 99(50): e23564, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327312

RESUMO

BACKGROUND: Peripheral neurotoxicity (PN) is a frequent side effect of oxaliplatin treatment, and also is its dose-limiting toxicity. Studies have confirmed that ω-3 polyunsaturated fatty acids (ω-3 PUFAs) had a neuroprotective effect. However, the efficacy of ω-3 PUFAs on the prevention of oxaliplatin-related neurotoxicity remains unclear. We assessed the effect of ω-3 PUFAs on the neurotoxicity in colon cancer patients treated by oxaliplatin combined with capecitabine. METHODS: In a randomized, double-blind, placebo-controlled study, 179 patients with colon cancer receiving oxaliplatin combined with capecitabine were recruited, and randomly assigned to take ω-3 PUFAs, 640 mg t.i.d during chemotherapy and 1 month after the end of the treatment or placebo. All patients were treated with chemotherapy for 6 treatment cycles. The incidence and severity of PN were evaluated, and the nerve conduction was measured before the onset of chemotherapy and 1 month after treatment. In addition, the quality of life was also accessed using Chinese version of European organization for research and treatment of cancer quality of life questionnaire. RESULTS: The incidence of PN in the ω-3 PUFAs group and placebo group was 52.22% and 69.66%, respectively (P = .017). In addition, there was a significant difference in the severity of PN between the 2 groups (P = .017). In terms of motor and sensory nerve conduction, the sensory action potentials amplitude of sural nerve in the ω-3 PUFAs group and placebo group after chemotherapy treatment were (15.01 ±â€Š3.14) and (13.00 ±â€Š3.63) µ V respectively, suggesting there was a significant difference in the 2 groups (P = .000). In addition, the mean score of the global health-status/quality of life was obviously higher in the ω-3 PUFAs group than that in the placebo group. CONCLUSION: ω-3 PUFAs seem to reduce the incidence and severity of oxaliplatin-related neurotoxicity, and improve the quality of patients' life, indicating it is expected to be a potential drug for the treatment of oxaliplatin-related neurotoxicity.


Assuntos
Capecitabina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/prevenção & controle , Oxaliplatina/toxicidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Capecitabina/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Síndromes Neurotóxicas/etiologia , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Qualidade de Vida , Inquéritos e Questionários
4.
Gan To Kagaku Ryoho ; 47(9): 1383-1385, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130706

RESUMO

A 70-year-old male with defecation difficulties was referred to our hospital. A colonoscopy and computed tomography revealed multiple advanced rectal cancers in the rectosigmoid and lower rectum with swollen lymph nodes. After 6 courses of neoadjuvant capecitabine and oxaliplatin and bevacizumab without radiotherapy(CapeOX plus BV therapy), a colonoscopy revealed that the tumors had significantly reduced. A low anterior laparoscopic resection with diverting ileostomy was performed. Histopathological examination showed no residual tumor cells or lymph node metastasis. A final diagnosis of pathological complete response was made. The patient has currently survived 1-year disease-free. Neoadjuvant CapeOX plus BV therapy can be a promising therapeutic option for locally advanced rectal cancer.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Humanos , Masculino , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Reto
5.
Anticancer Res ; 40(7): 4011-4015, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620645

RESUMO

BACKGROUND/AIM: The aim of this monocentric study was to evaluate the efficacy and tolerability of a polychemotherapy regimen based on gemcitabine, docetaxel, capecitabine, cisplatin (PDGX) as second-line for advanced pancreatic cancer after FOLFIRINOX. PATIENTS AND METHODS: Patients received FOLFIRINOX as first-line regimen were retrospectively identified between January 2016 and January 2019. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were treated in our center by PDGX. RESULTS: During this period, 18 patients received PDGX regimen as second-line therapy. Main grade 3 toxicities were hematologic, which required dose adaptation in 14/18 patients. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2,91 and 5,3 months, respectively. Total OS from the initiation of first-line was and 11,9 months. CONCLUSION: Second-line PDGX regimen after FOLFIRINOX failure is feasible, with notable toxicity profile and is associated with poor clinical outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Capecitabina/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Docetaxel/efeitos adversos , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Resultado do Tratamento
6.
Medicine (Baltimore) ; 99(25): e20809, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569228

RESUMO

RATIONALE: Pyrotinib is a novel dual pan-ErbB receptor tyrosine kinase inhibitor, approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, there was still limited information regarding specific effect of pyrotinib on HER2-positive MBC patients with phosphoinositol-3 kinase mutation. PATIENT CONCERNS: A 63-year-old woman accidentally discovered a left breast lesion. The breast cancer was diagnosed by biopsy of breast lesion and postoperative pathological examination in March, 2017. The patient was presented with HER2-positive (3+), invasive carcinoma of the left breast with lymph nodes and lung nodules metastasis, and the clinical stage was T4N2M1. However, the lesion continued to aggressive disease progression with the treatment of trastuzumab plus multiple chemotherapy regimens and traditional Chinese medicine. DIAGNOSES: The woman was diagnosed with invasive carcinoma of the left breast and lymph nodes and lung nodules metastasis. INTERVENTIONS: The patient received 6 cycles of pyrotinib in combination with capecitabine regularly. OUTCOMES: Progression free survival was more than 6 months, and the patient's efficacy evaluation was partial remission. LESSONS: Our clinical observations demonstrated that pyrotinib may be an effective treatment for patients with HER2-positive MBC.


Assuntos
Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Acrilamidas/administração & dosagem , Aminoquinolinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade
7.
Crit Rev Oncol Hematol ; 153: 102988, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32599374

RESUMO

This review aims to evaluate the role of chemotherapy-containing regimens in the treatment of advanced breast cancer (ABC), with the purpose to optimize selection, sequencing and duration of treatment with the currently available agents for clinical practice. Data from observational as well as randomized phase II and III studies were included. Chemotherapy yielded a median overall survival (OS) of 2 years in registration studies, with comparable efficacy of different agents. Combining chemotherapy agents did not yield OS improvement and caused greater toxicity compared with single-agent chemotherapy. Continuing chemotherapy till progression or unacceptable toxicity generated greater efficacy without detrimental impact on quality of life compared with a limited amount of cycles. In real-world studies, benefits after third-line chemotherapy were modest compared with first- and second-line. Furthermore, effects of previous chemotherapy predicted effects of next-line therapy in real-world. Physicians increasingly prescribed capecitabine or taxanes as first- or second-line chemotherapy over time.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Humanos , Qualidade de Vida , Taxoides/uso terapêutico
9.
PLoS One ; 15(6): e0234432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516350

RESUMO

The fraction retention non-inferiority hypothesis is often measured for the ratio of the effects of a new treatment to those of the control in medical research. However, the fraction retention non-inferiority test that the new treatment maintains the efficacy of control can be affected by the nuisance parameters. Herein, a heuristic procedure for testing the fraction retention non-inferiority hypothesis is proposed based on the generalized p-value (GPV) under normality assumption and heteroskedasticity. Through the simulation study, it is demonstrated that, the performance of the GPV-based method not only adequately controls the type I error rate at the nominal level but also is uniformly more powerful than the ratio test, Rothmann's and Wang's tests, the comparable extant methods. Finally, we illustrate the proposed method by employing a real example.


Assuntos
Interpretação Estatística de Dados , Desenvolvimento de Medicamentos/métodos , Modelos Estatísticos , Projetos de Pesquisa , Resultado do Tratamento , Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Simulação por Computador , Estudos de Equivalência como Asunto , Humanos , Neoplasias/tratamento farmacológico
10.
Crit Rev Oncol Hematol ; 151: 102975, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32464483

RESUMO

Patients with biliary tract cancer (BTC) have a high recurrence rate after complete surgical resection. To reduce the risk of recurrence and to improve survival, several chemotherapeutic agents that have shown to be active in locally advanced and metastatic BTC have been investigated in the adjuvant setting in prospective clinical trials. Based on the results of the BILCAP phase III trial, capecitabine was adapted as the standard of care by the ASCO clinical practice guideline. Ongoing randomized controlled trials mainly compare capecitabine with gemcitabine-based chemotherapy or chemoradiotherapy. This review provides an update of adjuvant therapy in BTC based on published data of phase II and III trials and ongoing randomized controlled trials (RCTs).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/terapia , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar/patologia , Humanos , Recidiva Local de Neoplasia , Estudos Prospectivos
11.
Cancer Chemother Pharmacol ; 85(5): 969-978, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32314029

RESUMO

PURPOSE: This study investigated the influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer (CRC) patients who received capecitabine-based adjuvant chemotherapy in real world. METHODS: A total of 315 CRC patients underwent R0 surgical resection and received capecitabine-based adjuvant chemotherapy were included. Clinical characteristics were collected from the hospital record system, prognosis was obtained by telephone follow-up. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of CRC patients were performed for the genotyping of polymorphism and mRNA expression of PD-L1, respectively. Analysis on the association between genotypes and prognosis was conducted. RESULTS: The median disease-free survival (DFS) of the 315 CRC patients was 5.1 years, the median overall survival (OS) was 6.0 years. Regarding the PD-L1 gene polymorphism analysis, the prevalence of 901T>C among the CRC patients was as follows: TT genotype 221 cases (70.16%), TC genotype 86 cases (27.30%), CC genotype 8 cases (2.54%), the minor allele frequency was 0.16, the distribution of three genotypes was in accordance with Hardy-Weinberg equilibrium (P = 0.915). Moreover, the prognosis analysis indicated that the median DFS of patients with TT and TC/CC genotype was 5.4 and 4.0 years, respectively (P = 0.008). The median OS of patients with the two genotypes was 6.4 and 5.0 years (P = 0.007). The multivariate Cox regression analysis showed that the TC/CC genotypes were an independent factor for DFS (odds ratio = 1.56, P = 0.018). Furthermore, the mRNA expression results indicated that the mRNA expression of PD-L1 in PBMC of the patients with TC/CC genotype was significantly higher than patients with TT genotype (P < 0.001). CONCLUSION: The prognosis of R0 resection CRC patients received capecitabine-based adjuvant chemotherapy in real world may be influenced by PD-L1 901T>C polymorphism through mediation of the mRNA expression of PD-L1.


Assuntos
Antígeno B7-H1/genética , Capecitabina/uso terapêutico , Colectomia/métodos , Neoplasias Colorretais , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante/métodos , China/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Prognóstico , Estudos Retrospectivos
12.
Eur J Cancer ; 130: 219-227, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32234665

RESUMO

BACKGROUND: The rationale for the evaluation of trametinib in advanced biliary cancer (BC) is based on the presence of mitogen-activated protein kinase alterations and on earlier promising results with MEK inhibitors in BC. METHODS: Patients with histologically proven BC who progressed on gemcitabine/platinum were randomised to trametinib daily (arm 1) versus fluoropyrimidine therapy (infusional 5-fluorouracil or oral capecitabine, arm 2). The primary end-point was overall survival (OS). Secondary end-points included progression free survival (PFS) and response rate. A planned interim futility analysis of objective response was performed on the first 14 patients registered to the trametinib arm. RESULTS: The study was stopped early based on the lack of measurable response in the trametinib arm. A total of 44 eligible patients were randomised (24 patients in arm 1 and 20 patients in arm 2). Median age was 62 years and the primary sites of tumour were cholangiocarcinoma (68%) and gallbladder (32%). The overall response rate was 8% (95% CI 0%-19%) in arm 1 versus 10% (95% CI 0%-23%) in arm 2 (p > .99) Median OS was 4.3 months for arm 1 and 6.6 months for arm 2. The median PFS was 1.4 months for arm 1 and 3.3 months for arm 2. CONCLUSIONS: This is the first prospective randomised study of a targeted agent versus chemotherapy for the second-line treatment of BC. In this unselected population, the interim analysis result of unlikely benefit with trametinib resulted in early closure.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Capecitabina/uso terapêutico , Fluoruracila/uso terapêutico , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Sistema Biliar/patologia , Capecitabina/farmacologia , Feminino , Fluoruracila/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Piridonas/farmacologia , Pirimidinonas/farmacologia
13.
BMC Cancer ; 20(1): 180, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131770

RESUMO

BACKGROUND: It is not known what combination of bevacizumab and chemotherapy agents is the best therapeutic regimen. Comparative study results among the efficacies of bevacizumab plus chemotherapy remain controversial in patients with HER2-negative metastatic breast cancer. METHODS: We searched Pubmed, Embase, and Cochrane Library Central Resister of Controlled Trials through were July 2019 for randomized controlled trials that evaluated the efficacy of bevacizumab plus chemotherapy in HER2-negative metastatic breast cancer. Data on included study characteristics, outcomes, and risk of bias were abstracted by two reviewers. RESULTS: A total of 16 RCT studies involving 5689 patients were included. The results showed that bevacizumab (Bev) - taxanes (Tax) - capecitabine (Cap) has highest-ranking and is probably more effective for prolonging progression-free survival (PFS) than Tax, Cap, Bev-Tax and Bev-Cap, which was no convincing differences among Bev-Cap-vinorelbine, Bev-Tax-everolimus, Bev-Tax-trebananib, Bev-exemestane, Bev-Cap-cyclophosphamide in Bev-containing regimens. For overall response rate (ORR), Bev-Tax-Cap is superior to Tax, Cap and Bev-Cap, while Bev-Tax-trebananib is superior to Cap. The cumulative probability ranking showed that Bev-Tax-Cap or Bev-Tax-trebananib may have best pathological response rate in HER2-negative metastatic breast cancer. CONCLUSION: Our results provide moderate quality evidence that bevacizumab-taxanes-capecitabine maybe the most effective bevacizumab plus chemotherapy on PFS and ORR in HER2-negative metastatic breast cancer, however it should be also considered that bevacizumab may add toxicity to chemotherapy and whether improve overall survival (OS) or not.


Assuntos
Bevacizumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Quimioterapia Combinada/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Metanálise em Rede , Receptor ErbB-2/metabolismo , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
14.
Neoplasma ; 67(3): 677-683, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32039629

RESUMO

Despite advances in the multimodal approach for rectal cancer, treatment-related side effects remain an important issue. From this perspective, a prospective trial was performed to investigate the feasibility of modulated electro-hyperthermia (mEHT) as a concomitant boost to preoperative chemoradiation in locally advanced rectal cancer. Seventy-six patients with cT3-4 or cT2N+ rectal cancer were enrolled consecutively. Whole pelvic radiotherapy of 40 Gy was delivered with a 2-Gy daily fraction. mEHT with 13.56 MHz frequency was boosted on a twice-weekly schedule concurrently with intravenous 5-fluorouracil or oral capecitabine. Surgical resection was planned 6-8 weeks after radiotherapy. The primary endpoint was the non-inferior treatment response rate assessed by pathologic downstaging and tumor regression. The secondary endpoint was acceptable toxicity during the preoperative treatment period. Sixty patients completed the planned treatment schedule. T- and N-downstaging was demonstrated in 40 patients (66.7%) and 53 patients (88.3%), respectively. Pathologic complete response was noted in 15.0% (9 patients) and 76.7% (46 patients) for T-stage and N-stage, respectively. Total or near total tumor regression was observed in 20 patients (33.3%). Grade ≥3 toxicity occurred only in hematologic assessment; one case (1.7%) of leukopenia and one case (1.7%) of anemia. Sixteen patients (26.7%) developed thermal toxicity, which was mostly Grade 1 (15 patients, 93.8%). The relatively low dose of 40 Gy radiation showed comparable pathologic treatment outcomes and tolerable toxicity profiles with the addition of mEHT, which may potentially replace part of the radiation dose in neoadjuvant treatment for rectal cancer.


Assuntos
Hipertermia Induzida , Cuidados Pré-Operatórios , Neoplasias Retais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/uso terapêutico , Quimiorradioterapia , Estudos de Viabilidade , Fluoruracila/uso terapêutico , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Prospectivos
15.
Br J Nurs ; 29(3): S4-S9, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053446

RESUMO

Metastatic HER2-positive breast cancer is an incurable disease with a poor prognosis. This article presents a critical appraisal of two treatments commonly used in the treatment of metastatic HER2-positive breast cancer: the oral chemotherapy drug, capecitabine, and the monoclonal antibody, trastuzumab. What follows is a critical discussion of the pharmacotherapeutics of capecitabine and trastuzumab, which considers their use both as single agents and as a combination regimen in the treatment of metastatic breast cancer. The implications of side effects of these drugs are discussed, both individually and in combination, as are the challenges these bring to the prescriber. The article evaluates the use of these agents and concludes that the combination of capecitabine and trastuzumab is an attractive treatment option for patients and for the prescriber.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Trastuzumab/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Humanos , Resultado do Tratamento
16.
Asia Pac J Clin Oncol ; 16(3): 180-186, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32077628

RESUMO

BACKGROUND: Capecitabine plus oxaliplatin (XELOX) as adjuvant therapy for gastric cancer (GC) reduces cancer recurrence and improves survival. S-1 plus oxaliplatin (SOX) is well-tolerated and effective against advanced GC, and also be used widely in adjuvant treatment. However, data comparing SOX and XELOX as adjuvant treatments are lacking. METHOD: Data on treatment modalities, adverse events, recurrence and metastasis were collected from 180 patients with stage II and III GC, who received SOX or XELOX after D2 gastrectomy between January 2012 and December 2015, and analyzed retrospectively. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Median follow was 52.9 months; 3-year DFS rate and overall survival (OS) rate were 75.2% and 67.6% (P = 0.359) and 81.2% and 83.3% (P = 0.77) in the SOX and XELOX groups, respectively. There was no significant difference in peritoneal metastasis rates in the SOX and XELOX groups (8.6% vs 15%, respectively; P = 0.232). Compound recurrent disease was associated with significantly shorter OS. Multivariate analysis identified metastatic lymph node ratio (LNR) as an independent prognostic factor for OS (P = 0.036; hazard ratio = 2.875; 95% confidence interval, 1.069-7.729); the LNR ≥17% group had inferior 3-year OS rate to the LNR <17% group (P = 0.001). The incidence of grades 3 and 4 adverse events was similar in both groups; however, grade ≥2 hand-foot syndrome was significantly less frequent in the SOX group (P = 0.01). CONCLUSION: SOX has similar survival benefits to XELOX and is well-tolerated in Chinese patients with GC following D2 gastrectomy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Quimioterapia Adjuvante/métodos , Oxaliplatina/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Capecitabina/farmacologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Oxaliplatina/farmacologia , Ácido Oxônico/farmacologia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Tegafur/farmacologia
17.
Trials ; 21(1): 89, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941523

RESUMO

BACKGROUND: A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects. METHODS/DESIGN: CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy. DISCUSSION: The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit. TRIAL REGISTRATION: ISRCTN, ISRCTN92755158, Registered on 17 February 2016.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Rádio (Elemento)/uso terapêutico , Administração Oral , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Humanos , Metástase Neoplásica/patologia , Radioisótopos/administração & dosagem , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Rádio (Elemento)/administração & dosagem , Rádio (Elemento)/efeitos adversos , Segurança , Resultado do Tratamento
18.
BMC Cancer ; 20(1): 57, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992260

RESUMO

BACKGROUND: This study aimed to evaluate the safety and feasibility of self-expanding metallic stent (SEMS) followed by neoadjuvant chemotherapy prior to elective surgery for obstructing left-sided colon cancer. METHODS: Eleven consecutive patients with obstructing left-sided colon cancer between May 2014 and November 2015 were included retrospectively. All patients received SEMS followed by neoadjuvant chemotherapy. The primary outcome measure was stoma and laparoscopic surgery. RESULTS: Chemotherapy was with two cycles of CAPOX (54.5%) or three cycles mFOLFOX6 (45.5%). Median serum albumin and hemoglobin levels before surgery were significantly higher than before neoadjuvant chemotherapy (p = 0.01 and p = 0.008 respectively) and before SEMS (p = 0.01 and p = 0.003 respectively). Median bowel wall thickness proximal to the upper edge of tumor was significantly more before neoadjuvant chemotherapy than before stent (p = 0.003), and significantly less before surgery than before neoadjuvant chemotherapy (p = 0.003). No patient underwent stoma creation. Laparoscopic surgery was performed in nine (81.8%) patients. No local recurrence or metastases developed over median cancer-specific follow-up of 44 months (range, 37-55 months). CONCLUSION: SEMS followed by neoadjuvant chemotherapy prior to elective surgery appears to be safe and well tolerated in patients with obstructing left-sided colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Obstrução Intestinal/cirurgia , Laparoscopia/instrumentação , Stents Metálicos Autoexpansíveis/efeitos adversos , Adulto , Idoso , Capecitabina/uso terapêutico , Neoplasias do Colo/metabolismo , Tratamento Farmacológico , Estudos de Viabilidade , Feminino , Fluoruracila , Humanos , Obstrução Intestinal/metabolismo , Leucovorina , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo , Resultado do Tratamento
19.
J Chromatogr Sci ; 57(10): 892-900, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31609432

RESUMO

Capecitabine is a prodrug of 5-fluorouracil, employed as a monotherapy or combination chemotherapy agent for treatment of colorectal cancer. Combination therapy of capecitabine consists of oxaliplatin, and hence, it becomes essential to determine that co-administration does not affect its metabolism. High-performance liquid chromatography and high-performance thin-layer chromatography methods were developed and validated to determine the plasma concentration of capecitabine. In this study, blood samples from 12 patients with colorectal cancer were collected and analyzed by both methods with a reference internal standard. Two groups consisting of six patients each were formed: the first group was treated with capecitabine monotherapy, the second group with capecitabine + oxaliplatin combination therapy. The results of analysis from both the methods indicated that there is no significant drug-drug interaction. The co-administration of oxaliplatin did not affect the metabolism of capecitabine. Both assay methods were compared for their sensitivity, robustness and specificity. It was found that both the assay methods were suitable for therapeutic drug monitoring of capecitabine.


Assuntos
Antineoplásicos , Capecitabina , Cromatografia Líquida de Alta Pressão/métodos , Neoplasias Colorretais/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Capecitabina/sangue , Capecitabina/farmacocinética , Capecitabina/uso terapêutico , Cromatografia em Camada Delgada , Interações Medicamentosas , Estabilidade de Medicamentos , Humanos , Limite de Detecção , Modelos Lineares , Oxaliplatina/sangue , Oxaliplatina/farmacocinética , Oxaliplatina/uso terapêutico , Reprodutibilidade dos Testes
20.
Int J Cancer ; 146(5): 1359-1368, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31241775

RESUMO

Tumor heterogeneity was associated with treatment outcome of metastatic cancers but few studies have examined whether tumor heterogeneity in circulating tumor DNA (ctDNA) can be used to predict treatment outcome. ctDNA analysis was performed in 37 HER2-positive metastatic breast cancer patients treated with pyrotinib. Patients with high tumor heterogeneity had significantly worse PFS outcomes, with a median PFS of 30.0 weeks vs. 60.0 weeks for patients with low tumor heterogeneity (hazard ratio [HR], 2.9; p = 0.02). Patients with trunk resistance mutations receiving pyrotinib monotherapy had worse outcomes (HR, 4.5; p = 0.03), with a median PFS of 7.8 weeks vs. 27.4 weeks for those with branch resistance mutations or without any resistance mutations in baseline ctDNA. Longitudinal monitoring of 21 patients during treatment showed that the molecular tumor burden index ([mTBI] a measure of the percentage of ctDNA in samples) was positively correlated with tumor size as evaluated by computed tomography (p < 0.0001, Pearson r = 0.52) and detected disease progression 8-16 weeks earlier. Our current findings suggested that ctDNA could be used to assess tumor heterogeneity and predict treatment outcomes. Furthermore, the mTBI is better for assessing therapeutic response than single gene mutations and might supplement the current therapeutic response evaluation system.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , DNA Tumoral Circulante/genética , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Adulto , Aminoquinolinas/farmacologia , Aminoquinolinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Capecitabina/farmacologia , Capecitabina/uso terapêutico , DNA Tumoral Circulante/sangue , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Adulto Jovem
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