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1.
Anticancer Res ; 41(1): 391-402, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419836

RESUMO

BACKGROUND/AIM: Oxaliplatin-based chemotherapy is associated with hepatic sinusoidal obstruction syndrome (SOS). PATIENTS AND METHODS: We analyzed patients from two prospective trials, in which capecitabine/oxaliplatin (XELOX, 8 cycles; n=51) and S-1/oxaliplatin [SOX, continuous (SOX-C, n=50), or intermittent (discontinuation after cycle 6 and restart on progression, SOX-I, n=50)] were administered. We compared severity (splenomegaly, thrombocytopenia, liver enzyme levels, and hepatic parenchymal heterogeneity), clinical significance (delay or dose-reduction of chemotherapy), and reversibility of SOS (splenomegaly and thrombocytopenia after stopping chemotherapy) between SOX and XELOX in gastric cancer patients. RESULTS: SOX was more likely to be associated with splenomegaly, thrombocytopenia, hyperbilirubinemia, and hepatic parenchymal heterogeneity than XELOX. Splenomegaly was partially reversible after stopping chemotherapy in both regimens, but recovery rate was lower in SOX. Proportion of delayed or dose-reduced chemotherapy cycles due to thrombocytopenia was significantly higher in SOX-C than in XELOX. CONCLUSION: S-1 combination is more likely to worsen oxaliplatin-induced hepatic sinusoidal injuries than capecitabine in gastric cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hepatopatia Veno-Oclusiva/etiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico , Adulto , Biomarcadores , Capecitabina/administração & dosagem , Gerenciamento Clínico , Combinação de Medicamentos , Feminino , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Incidência , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Ácido Oxônico/administração & dosagem , Estudos Retrospectivos , Baço/patologia , Esplenectomia , Tegafur/administração & dosagem , Resultado do Tratamento
2.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(2): 128-137, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33508918

RESUMO

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.


Assuntos
Adenocarcinoma , Quimiorradioterapia Adjuvante , Junção Esofagogástrica , Terapia Neoadjuvante , Neoplasias Gástricas , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Gastrectomia , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Oxaliplatina/administração & dosagem , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(2): 138-144, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33508919

RESUMO

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.


Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Combinação de Medicamentos , Humanos , Oxaliplatina/administração & dosagem , Ácido Oxônico/administração & dosagem , Radioterapia , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Resultado do Tratamento
4.
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
5.
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
7.
Anticancer Res ; 40(7): 3905-3913, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620631

RESUMO

BACKGROUND/AIM: Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. PATIENTS AND METHODS: Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. RESULTS: A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. CONCLUSION: Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Vinorelbina/administração & dosagem , Administração Oral , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/patologia , Capecitabina/administração & dosagem , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Estudos Retrospectivos
8.
Int J Clin Oncol ; 25(9): 1635-1643, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32494981

RESUMO

BACKGROUND: We previously reported the HERBIS-4A phase II trial comparing S-1 plus cisplatin (SP) with capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2-negative advanced gastric cancer (GC). We performed a pooled analysis of HERBIS-4A and HERBIS-2, the phase II trial comparing SP with XP in HER2-negative recurrent GC patients with a recurrence-free interval after S-1 adjuvant therapy of ≥ 6 months. PATIENTS AND METHODS: Patients were randomly assigned to receive either SP [S-1 (40-60 mg twice daily for 21 days) plus cisplatin (60 mg/m2 on day 8), every 5 weeks] or XP [capecitabine (1000 mg/m2 twice daily for 14 days) plus cisplatin (80 mg/m2 on day 1), every 3 weeks]. RESULTS: In the pooled analysis, SP (n = 44-50) showed a longer progression-free survival [6.4 versus 5.1 months; hazard ratio (HR), 0.666; P = 0.062], overall survival (14.8 versus 10.6 months; HR, 0.695; P = 0.099), and time to treatment failure (4.6 versus 3.6 months; HR, 0.668; P = 0.045) as well as a higher disease control rate (86.4% versus 68.1%, P = 0.149) compared with XP (n = 47-51). A significant survival advantage for SP over XP was apparent in patients with a performance status of 0, a differentiated-type tumor histology, or a primary tumor localization to the upper portion of the stomach. CONCLUSION: Our pooled analysis supports the use of SP in the first-line setting for patients with HER2-negative advanced or recurrent GC with a recurrence-free interval of ≥ 6 months. CLINICAL TRIAL REGISTRATION: The HERBIS-2 trial was registered with UMIN-CTR as UMIN000006105.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Ácido Oxônico/administração & dosagem , Intervalo Livre de Progressão , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Resultado do Tratamento
9.
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
10.
Int J Clin Oncol ; 25(8): 1515-1522, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32409917

RESUMO

BACKGROUND: Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. METHODS: Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3-79.3) and the DCR was 82.8% (95% confidence interval 64.2-94.2). The RR for oxaliplatin-free interval was 100.0% in months 6-12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. CONCLUSION: Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
Radiol Med ; 125(12): 1216-1224, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32410063

RESUMO

PURPOSE: To determine whether MRI T2-weighted sequences-based texture analysis (TA) can predict histopathological tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemo-radiotherapy (nCRT). METHODS: Data on patients undergoing curative-intent surgery for LARC were collected. Patients with a complete pathological response, or TRG1 according to Mandard's system were classified as responders, while patients with TRG ≥ 2 were classified as non-responders. Tumor TA was performed on each patient's paraxial T2w MRI in both pre- and post-nCRT scans, in order to extract histograms, gray-level co-occurrence matrix (GLCM) and run-length matrix (RLM) texture parameters. For features that showed a significant difference between the two groups, a receiver operating characteristic (ROC) curve was drawn. RESULTS: Overall, 62 patients with LARC, treated with nCRT and resective surgery at our institution between 2013 and 2019 were identified. Only post-nCRT GLCM maximum probability showed a significant difference between the two groups (2909 ± 4479 in responders vs. 6515 ± 8990 in non- responders; p = 0.039); at the ROC curve, Youden index showed a sensitivity of 14% and a specificity of 100% for this parameter. CONCLUSIONS: MRI T2-weighted sequences-based TA was not effective in predicting pathological complete response to nCRT in patients with LARC. Further studies are needed to thoroughly investigate the potential of MRI TA in this setting.


Assuntos
Quimiorradioterapia Adjuvante , Imagem por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Dosagem Radioterapêutica , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
12.
Indian J Gastroenterol ; 39(2): 204-210, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32406009

RESUMO

BACKGROUND: Eppikajututo (TJ-28, a Kampo medicine) is effective against rheumatoid arthritis and eczema. We conducted a randomized comparative trial to assess the efficacy of TJ-28 for preventing hand-foot syndrome (HFS) as a complication of adjuvant chemotherapy using capecitabine. METHODS: The present study was a multi-institutional randomized-controlled trial (UMIN000005899). Colorectal cancer patients scheduled to receive capecitabine chemotherapy as adjuvant therapy were randomly assigned to receive TJ-28 (7500 mg/day) or oral pyridoxine (60 mg/day). Patients were monitored for the development of grade ≥ 2 HFS according to the National Cancer Institute Common Toxicity Criteria until chemotherapy completion. RESULTS: Twenty-two patients were enrolled in this study. The relative dose intensity of capecitabine was 76.2% in the TJ-28 group and 68.2% in the pyridoxine group. Grade ≥ 2 HFS developed in 6 (50.0%) of 12 TJ-28 patients and in 4 (40.0%) of 10 pyridoxine patients. Chemotherapy treatment failure was observed in seven patients, mainly due to HFS, liver dysfunction, diarrhea, and neutropenia. Chemotherapy treatment failure due to HFS occurred in none of the TJ-28 group and 2 patients (20.0%) in the pyridoxine group (p = 0.114). CONCLUSION: Capecitabine-associated HFS was not markedly prevented by TJ-28 compared with pyridoxine. However, TJ-28 might support the continuation of chemotherapy with capecitabine. Further studies are warranted to clarify the benefits of TJ-28.


Assuntos
Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/terapia , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/prevenção & controle , Resultados Negativos , Preparações Farmacêuticas/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piridoxina/administração & dosagem , Adulto Jovem
13.
Pharm Res ; 37(5): 89, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382808

RESUMO

PURPOSE: Capecitabine is an oral pre-pro-drug of the anti-cancer drug 5-fluorouracil (5-FU). The biological activity of the 5-FU degrading enzyme, dihydropyrimidine dehydrogenase (DPD), and the target enzyme thymidylate synthase (TS), are subject to circadian rhythmicity in healthy volunteers. The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety, pharmacokinetics (PK) and pharmacodynamics (PD) of capecitabine therapy adapted to this circadian rhythm (chronomodulated therapy). METHODS: Patients aged ≥18 years with advanced solid tumours potentially benefitting from capecitabine therapy were enrolled. A classical dose escalation 3 + 3 design was applied. Capecitabine was administered daily without interruptions. The daily dose was divided in morning and evening doses that were administered at 9:00 h and 24:00 h, respectively. The ratio of the morning to the evening dose was 3:5 (morning: evening). PK and PD were examined on treatment days 7 and 8. RESULTS: A total of 25 patients were enrolled. The MTD of continuous chronomodulated capecitabine therapy was established at 750/1250 mg/m2/day, and was generally well tolerated. Circadian rhythmicity in the plasma PK of capecitabine, dFCR, dFUR and 5-FU was not demonstrated. TS activity was induced and DPD activity demonstrated circadian rhythmicity during capecitabine treatment. CONCLUSION: The MTD of continuous chronomodulated capecitabine treatment allows for a 20% higher dose intensity compared to the approved regimen (1250 mg/m2 bi-daily on day 1-14 of every 21-day cycle). Chronomodulated treatment with capecitabine is promising and could lead to improved tolerability and efficacy of capecitabine.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Capecitabina/administração & dosagem , Capecitabina/farmacologia , Cronoterapia Farmacológica , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Capecitabina/efeitos adversos , Capecitabina/sangue , Ritmo Circadiano , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Feminino , Fluoruracila/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Timidilato Sintase/metabolismo , Uridina Trifosfato/análogos & derivados , Uridina Trifosfato/sangue
14.
Am J Clin Oncol ; 43(5): 305-310, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32343515

RESUMO

OBJECTIVES: Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC. METHODS: This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m, oxaliplatin 80 mg/m on day 1, CP 1000 mg/m twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate. RESULTS: Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed. CONCLUSIONS: First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Adulto , Idoso , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Carcinoma Neuroendócrino/mortalidade , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
15.
Int J Clin Oncol ; 25(6): 1123-1129, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232692

RESUMO

PURPOSE: Peripheral neuropathy (PN) is an intractable side effect of oxaliplatin, with no effective prophylaxis so far. Ninjin'yoeito (NYT), a Kampo medicine, is protective against oxaliplatin-induced neuronal cell injury in vitro and ameliorates oxaliplatin-induced PN in vivo. Thus, this randomized controlled trial was aimed at clarifying NYT's prophylactic effect for oxaliplatin-induced cumulative PN. METHODS: 52 patients with colorectal cancers of pathological stage 3 received postoperative adjuvant chemotherapy with the CapeOX regimen: eight cycles of capecitabine (2400 mg/m2) plus oxaliplatin (130 mg/m2) at 3-week intervals. They were randomly assigned to NYT administration and non-administration groups. NYT (9.0 g/day) was administered from day 1 of cycle 1 in the NYT group. The NYT was administered orally daily throughout each cycle. The primary endpoint was the grade of cumulative PN at the end of eight cycles. The secondary endpoints included relative dose intensity (RDI) of oxaliplatin, recurrence-free survival (RFS), and overall survival (OS). RESULTS: 40 patients (n = 20 in both groups) completed 8 chemotherapy cycles. The incidence of grade 2 or greater cumulative PN at the 8th chemotherapy cycle was significantly lower in the NYT group (2/20, 10.0%) than in the control group (11/20, 55.0%, P < 0.01). RDI of oxaliplatin was significantly higher in the NYT group than in the control group (P = 0.02). RFS and OS were better in the NYT group than in the control group, but the difference was not significant. CONCLUSIONS: NYT may reduce the incidence of oxaliplatin-induced cumulative PN and facilitate maintenance of the CapeOX dosing regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Panax , Período Pós-Operatório , Taxa de Sobrevida , Resultado do Tratamento
16.
BMC Med Genet ; 21(1): 76, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272879

RESUMO

BACKGROUND: Despite recent findings that epithelial cell adhesion molecule (EPCAM) deletions can cause Lynch syndrome (LS), its clinical characteristics are still unknown. We present the first case of ileum cancer in a patient with germline EPCAM gene deletion, which was discovered during ovarian tumor surgery. CASE PRESENTATION: A 59-year-old woman presented with a history of colon cancer occurring at 38 and 55 years old. Five of her siblings had a history of colon cancer, and an elder sister had confirmed LS. As imaging examination revealed an ovarian tumor, and we performed hysterectomy and bilateral salpingo-oophorectomy. Careful observation during surgery revealed a cherry-sized tumor in the ileum, prompting partial ileal resection. Pathological examination showed the ovarian tumor to be a metastasis of ileum cancer. Genetic testing with blood-relative information using multiplex ligation-dependent probe amplification showed EPCAM exons 8 and 9 deletions, confirming LS. The patient received adjuvant chemotherapy with CAPOX (capecitabine and oxaliplatin) and has remained disease-free for 24 months. CONCLUSIONS: We were fortunate to identify ileum cancer that would have been difficult to find preoperatively through careful observation during ovarian tumor surgery and successfully treated the patient by using surgical resection and CAPOX chemotherapy. When treating patients with hereditary cancer syndromes including LS, we should keep all associated cancers in mind.


Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Molécula de Adesão da Célula Epitelial/genética , Neoplasias do Íleo , Neoplasias Ovarianas , Ovariectomia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Capecitabina/administração & dosagem , Neoplasias Colorretais Hereditárias sem Polipose/tratamento farmacológico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Terapia Combinada , Feminino , Mutação em Linhagem Germinativa , Humanos , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Íleo/genética , Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/secundário , Neoplasias Ovarianas/cirurgia , Oxaliplatina/administração & dosagem , Linhagem , Deleção de Sequência , Resultado do Tratamento
17.
PLoS One ; 15(3): e0229900, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142532

RESUMO

BACKGROUND: In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed. METHODS: An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS. RESULTS: Phase-A enrolled 128 patients; median age was 64 years (range: 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI: 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI: 7.9-10.8) for Phase-A and 6.7 months (95% CI: 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI: 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group. CONCLUSIONS: Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01588990; posted May 1, 2012.


Assuntos
Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Inflamação/tratamento farmacológico , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/efeitos adversos , Biomarcadores Tumorais/genética , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Inflamação/genética , Inflamação/patologia , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaloacetatos/administração & dosagem , Pesquisa Médica Translacional
18.
Cancer Immunol Immunother ; 69(7): 1253-1263, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32170378

RESUMO

BACKGROUND AND OBJECTIVE: Activation of the immune checkpoints and expression of chemokines and chemokine receptors have been reported to promote HCC progression. This study aimed to assess the differential expression of Tim-3, PD-1, and CCR5 on peripheral blood lymphocytes from patients with HCV-related HCC and correlate their expression with the treatment outcomes. PATIENTS AND METHODS: The study incorporated 40 patients with chronic HCV-related HCC and 40 healthy controls. Patients were radiologically assessed for hepatic focal lesions and portal vein thrombosis. Response to HCC treatment and overall survival (OS) outcomes were determined. The expression of Tim-3, PD-1, and CCR5 among CD19+, CD4+, and CD8+ lymphocytes was assessed by flow cytometry. RESULTS: Higher frequencies of CD4+ and CD8+ cells expressing each of Tim-3 and PD-1 and PD-1+CD19+ cells were observed in the HCV-related HCC patients in comparison with controls. The highest expression of Tim-3 and PD-1 was by the CD8+ cells. Strong relations were detected among PD-1+CD19+, PD-1+CD4+ and PD-1+CD8+ cells. Elevated levels of PD-1+ lymphocytes were significantly associated with poor treatment response and shorter OS. CONCLUSION: Modulation of the expression of immune checkpoints as Tim-3 and PD-1, and of CCR5 on T cells is somehow related to HCC. CD8+ T cells expressing PD-1 were the most relevant to HCC prognosis (OS and treatment response) and could represent a promising target for immune therapy against HCC. Future studies need to focus on exploring PD-1+ B cells and Tim-3+CD4+ cells, which seem to play a significant role in the pathogenesis of HCC.


Assuntos
Linfócitos B/metabolismo , Carcinoma Hepatocelular/mortalidade , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Hepatite C/complicações , Receptor de Morte Celular Programada 1/metabolismo , Receptores CCR5/metabolismo , Linfócitos T/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Capecitabina/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sorafenibe/administração & dosagem , Taxa de Sobrevida
19.
Oncol Res Treat ; 43(4): 153-159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32187596

RESUMO

BACKGROUND: The aim of the current study was to estimate two protocols for HER2-negative locally recurrent or metastatic breast cancer patients, bevacizumab combined with paclitaxel versus bevacizumab combined with capecitabine, from the economic view. METHODS: The process of HER2-negative locally recurrent or metastatic breast cancer treated with bevacizumab combined with paclitaxel or bevaciz-umab combined with capecitabine made up the decision model in our analysis. The primary objective was to show the incremental cost-effectiveness ratio (ICER). The critical parameters and the robustness of the model on the results of the analysis were assessed by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS: In the analysis, quality-adjusted life year (QALY) increased by 0.4 with bevacizumab plus paclitaxel compared with bevacizumab plus capecitabine, and incremental cost of USD 4,340.46. Therefore, the ICER was USD 27,252.875. The ICER exceeded the commonly accepted willingness to pay on the recommendation of the World Health Organization, which is defined as 3 times of the gross domestic product per capita of China in the model (USD 25,840.88 per QALY). On univariate analysis, it is found that the most significant affecting factor is the cost of progression-free survival state in the bevacizumab plus paclitaxel group. Besides, bevacizumab plus paclitaxel had a 47.8% probability of being cost-effective versus bevacizu-mab plus capecitabine according to probabilistic sensitivity analysis. CONCLUSIONS: Based on the results of the analysis, bevacizumab plus paclitaxel is unlikely to be a cost-effective option for patients with HER2-negative locally recurrent or metastatic breast cancer compared with bevacizumab plus capecitabine.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/economia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/economia , Receptor ErbB-2/metabolismo , Bevacizumab/administração & dosagem , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Feminino , Seguimentos , Humanos , Cadeias de Markov , Metástase Neoplásica , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Paclitaxel/administração & dosagem , Prognóstico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida
20.
BMJ Case Rep ; 13(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32139448

RESUMO

A 49-year-old male carcinoma rectum patient was treated with neoadjuvant FOLFOX (folinic acid, fluorouracil (5-FU) and oxaliplatin) chemotherapy, chemoradiotherapy with capecitabine, surgery and adjuvant FOLFOX. On follow-up, the patient developed a metabolically active liver lesion mimicking metastasis. Liver biopsy and histopathology showed sinusoidal dilatation with non-caseating granulomas. Follow-up fluorodeoxyglucose positron-emission tomography CT scan demonstrated increase in size of the lesion with metabolic activity suspicious of metastasis. The patient underwent segmental liver resection and histopathology showed non-necrotising granuloma with no evidence of malignancy. It is crucial to consider potential side effects of chemotherapeutic agents and have an unbiased approach when evaluating new liver lesions during post treatment follow-up of colorectal cancer. A multidisciplinary tumour board approach comprising of gastroenterologists, medical oncologists, pathologists, radiologists and surgeons is suggested in the management of such patients. The patient is currently doing well and on regular follow-up.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Granuloma/induzido quimicamente , Neoplasias Retais/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Diagnóstico Diferencial , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos
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