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1.
Int J Clin Oncol ; 26(9): 1611-1618, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34297245

RESUMO

BACKGROUND: For advanced tumors that lack specific oncogenic alteration and are resistant to chemotherapy, anti-angiogenesis therapy or immunotherapy or a combination of the two are the most important treatments. Anlotinib is a newly developed oral small molecule receptor tyrosine kinases inhibitor with the potency of inhibiting tumor angiogenesis. This was an open-label, single-arm, phase 2 study to validate the efficacy and safety of anlotinib in patients with various cancer types. METHODS: Patients with advanced malignancy who have failed previous therapies or lack effective treatment choices received daily oral administration of 12 mg anlotinib on days 1-14 every 3 weeks until disease progression, intolerable toxicity or physician decision. The primary endpoint was objective response rate (ORR). RESULTS: A total of 93 eligible patients with 26 different cancer types were enrolled. The overall ORR was 21.5%. The median PFS was 5.7 months and median OS was 12.0 months. The most common treatment-related AE of all grades and of grade 3 was both hypertriglyceridemia at an incidence of 40.9% and 5.4%, respectively. CONCLUSIONS: Anlotinib exhibits objective efficacy and safety in advanced malignancy and might be a possible treatment option for many types of cancer patients who have failed prior treatment and with no optimal therapy regimen.

2.
Chin J Cancer Res ; 33(1): 103-114, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33707933

RESUMO

OBJECTIVE: This study evaluated the safety and preliminary efficacy of vorolanib, a novel tyrosine kinase inhibitor, for treatment of patients with advanced solid tumors. METHODS: During dose escalation, patients received increasing doses of oral vorolanib (50-250 mg once daily) in cycles of four weeks for up to one year. During dose expansion, patients received recommended doses (100 and 200 mg) in 4-week cycles. The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose (RP2D). The severity and type of adverse drug reactions (ADRs) were assessed using the Common Terminology Criteria for Adverse Events version 4.0. The second endpoint was preliminary efficacy in terms of objective response and progression-free survival (PFS). RESULTS: No dose-limiting toxicity occurred during dose escalation (50-250 mg). Five (26.3%) patients in the escalation cohort (n=19) and 12 (48.0%) in the expansion cohort (n=25) experienced grade 3 ADRs. The most common ADRs were hair color changes, fatigue, portal hypertension, hypertriglyceridemia, and proteinuria. During dose expansion, the patients treated with 200 mg and 100 mg (once daily) showed an objective response rate of 22.2% and 5.9%, respectively; the disease control rate was 88.9% and 73.3%, respectively; the median PFS was 9.9 [95% confidence interval (95% CI): 7.4-not reached] months and 3.8 (95% CI: 1.9-not reached) months, respectively. CONCLUSIONS: Oral vorolanib at a dose of 200 mg (once daily) exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors. The RP2D for vorolanib was determined to be 200 mg as a daily regimen.

3.
BMC Cancer ; 20(1): 219, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171288

RESUMO

BACKGROUND: We performed a pooled analysis of the COMPARZ study assessing efficacy and safety of pazopanib versus sunitinib in treatment-naïve Chinese patients with locally advanced and/or metastatic renal cell carcinoma (a/mRCC). METHODS: In the COMPARZ study, patients were randomized (1:1) to receive pazopanib 800 mg once daily (QD) continuously or sunitinib 50 mg QD in 6-week cycles (4 weeks on, 2 weeks off). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), and safety. PFS and ORR were assessed by independent review committee (IRC) and local investigators. RESULTS: Of the 209 Chinese patients (pazopanib, [n = 109] and sunitinib, [n = 100]), 155 (74%) were males and median age was 57 years (range, 18-79). Median PFS was 13.9 months for pazopanib versus 14.3 months for sunitinib per investigator assessment and 8.3 months in both arms per IRC assessment; PFS hazard ratio was 1.17 (investigator) and 0.99 (IRC). Median OS was not reached in pazopanib arm and was 29.5 months in sunitinib arm. ORR was significantly higher in pazopanib arm versus sunitinib arm (investigator: 41% versus 23% [P = 0.0052]; IRC: 35% versus 20% [P = 0.0203]). Pazopanib was generally well tolerated in Chinese patients with a/mRCC. Most frequent AEs in the pazopanib arm were diarrhea and hair color changes whereas the most frequent AEs in the sunitinib arm were decreased platelets, decreased neutrophil count, and thrombocytopenia. CONCLUSION: The results of the pooled analysis were consistent with the overall population in the COMPARZ study, and confirmed similar PFS and OS of pazopanib and sunitinib in the Chinese patients. TRIAL REGISTRATION: clinical trials.gov, NCT00720941 (August 14, 2008) and NCT01147822 (May 19, 2010).


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Sunitinibe/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/epidemiologia , China/epidemiologia , Feminino , Humanos , Indazóis , Neoplasias Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sunitinibe/administração & dosagem , Sunitinibe/efeitos adversos , Adulto Jovem
4.
Oncologist ; 24(8): e702-e708, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30902918

RESUMO

BACKGROUND: Anlotinib is a tyrosine kinase inhibitor inhibiting angiogenesis. This multicenter, randomized phase II trial aimed to investigate the efficacy and safety of anlotinib in comparison with sunitinib as first-line treatment for patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Patients with mRCC from 13 clinical centers were randomly assigned in a 2:1 ratio to receive anlotinib (n = 90) or sunitinib (n = 43). Anlotinib was given orally at a dose of 12 mg once daily (2 weeks on/1 week off), and sunitinib was given orally at 50 mg once daily (4 weeks on/2 weeks off). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: The median PFS was similar with anlotinib and sunitinib (17.5 vs. 16.6 months, p > .05). The median OS (30.9 vs. 30.5 months, p > .05), ORR (30.3% vs. 27.9%), and 6-week DCR (97.8% vs. 93.0%) were similar in the two groups. Adverse events (AEs) of grade 3 or 4 were significantly less frequent with anlotinib than with sunitinib (28.9% vs. 55.8%, p < .01), especially in terms of thrombocytopenia and neutropenia. AEs occurring at a lower frequency with anlotinib were hand-foot syndrome, eyelid edema, hair depigmentation, skin yellowing, neutropenia, thrombocytopenia, and anemia. The incidence of serious AEs was lower with anlotinib than with sunitinib. CONCLUSION: The clinical efficacy of anlotinib was similar to that of sunitinib as the first-line treatment for mRCC, but with a more favorable safety profile. IMPLICATIONS FOR PRACTICE: This study evaluated the efficacy and safety of anlotinib for the first-line treatment of metastatic renal cell carcinoma. Anlotinib, which was developed independently in China, is a new tyrosine kinase inhibitor inhibiting multiple kinases involved in angiogenesis and tumor proliferation. Results indicated that the efficacy of anlotinib is comparable to and the safety is better than that of sunitinib.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Indóis/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Quinolinas/administração & dosagem , Sunitinibe/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Sunitinibe/efeitos adversos
5.
Future Oncol ; 15(1): 53-63, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30058839

RESUMO

AIM: Efficacy/safety of first-line axitinib in Asian patients with metastatic renal cell carcinoma. METHODS: Patients were assigned (2:1) to 5-mg axitinib (n = 48) or 400-mg sorafenib (n = 24) twice daily. Primary end point was progression-free survival. Objective response rate, overall survival and adverse events were also assessed. RESULTS: For axitinib versus sorafenib, hazard ratio for progression-free survival was 0.652 (95% CI: 0.340-1.252; p = 0.0989), objective response rate was higher (35.4 vs 16.7%; p = 0.0495), overall survival longer (hazard ratio: 0.739; 95% CI: 0.397-1.375; p = 0.1683). Palmar-plantar erythrodysesthesia (57.4%), diarrhea (55.3%), hypertension (51.1%) were commonest adverse events with axitinib; palmar-plantar erythrodysesthesia (50.0%) with sorafenib. CONCLUSION: Axitinib improved efficacy in Asian patients with metastatic renal cell carcinoma; adverse events were consistent with previous findings.


Assuntos
Antineoplásicos/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Sorafenibe/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Povo Asiático , Axitinibe/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Sorafenibe/efeitos adversos , Resultado do Tratamento
6.
Future Oncol ; 14(18): 1835-1845, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29717651

RESUMO

AIM: We report the first prospective study of sunitinib for metastatic renal cell carcinoma (mRCC) in China. METHODS: Chinese mRCC patients received first-line sunitinib 50 mg daily (4/2 regimen). Overall survival (OS), progression-free survival (PFS), objective response rate and safety were assessed. Potential efficacy biomarkers were explored in post hoc analyses. RESULTS: Median PFS was 61.7 weeks; median OS was 133.4 weeks; objective response rate was 31.1%. Most frequent adverse events (AEs) were: hand-foot syndrome (63.8%), decreased white blood cell count (52.4%), fatigue (51.4%) and decreased platelet count (51.4%). AEs were identified that predicted longer PFS and OS. CONCLUSION: Sunitinib showed efficacy and manageable AE profile in treatment-naive Chinese mRCC patients. Larger prospective studies are required to confirm identified AEs as predictors of efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Sunitinibe/uso terapêutico , Adulto , Idoso , Carcinoma de Células Renais/mortalidade , China , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Resultado do Tratamento
7.
Cancer Sci ; 108(10): 2045-2051, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28763145

RESUMO

A phase II study of S-1 plus leucovorin (LV) given in a 4-week schedule (2 weeks' administration followed by 2 weeks' rest) for patients with untreated metastatic colorectal cancer (mCRC) showed that the combination was effective, but grade 3 toxicities (diarrhea, stomatitis and anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2-week schedule of S-1 plus LV. Patients with mCRC received oral S-1 (40-60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week's rest. Treatment was repeated until disease progression or unacceptable toxicity. The primary endpoint was response rate. The pharmacokinetics of S-1 and LV in Chinese patients were evaluated on day 1 of the first cycle. Seventy-three patients were enrolled in Japan and China. Of 71 eligible patients, the response rate was 53.5%, and the disease control rate was 83.1%. Median progression-free survival and median overall survival were 6.5 and 24.3 months, respectively. The incidences of grade 3 toxicities were diarrhea 8.3%, stomatitis 8.3%, anorexia 2.8% and neutropenia 9.7%. There were no treatment-related deaths. The pharmacokinetics profiles of S-1 plus LV in Chinese patients were similar to those in Japanese patients. This 2-week schedule of S-1 plus LV showed good efficacy and better tolerability than the 4-week schedule. This therapy will be the base regimen for mCRC to be added by other cytotoxic or molecular-targeted drugs. The optimized treatment schedule for S-1 plus LV was 1 week on and 1 week off.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Leucovorina/administração & dosagem , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/induzido quimicamente , Anorexia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Japão , Leucovorina/efeitos adversos , Leucovorina/farmacocinética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Ácido Oxônico/efeitos adversos , Ácido Oxônico/farmacocinética , Estomatite/induzido quimicamente , Estomatite/epidemiologia , Análise de Sobrevida , Tegafur/efeitos adversos , Tegafur/farmacocinética , Resultado do Tratamento
8.
N Engl J Med ; 369(8): 722-31, 2013 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-23964934

RESUMO

BACKGROUND: Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. METHODS: We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life. RESULTS: Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons). CONCLUSIONS: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib. (Funded by GlaxoSmithKline Pharmaceuticals; COMPARZ ClinicalTrials.gov number, NCT00720941.).


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Inibidores da Angiogênese/efeitos adversos , Carcinoma de Células Renais/secundário , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Indazóis , Indóis/efeitos adversos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Qualidade de Vida , Sulfonamidas/efeitos adversos , Sunitinibe
9.
BMC Cancer ; 16: 68, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26857702

RESUMO

BACKGROUND: The ToGA study showed that trastuzumab plus chemotherapy prolonged median survival in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Among chemotherapy options, oxaliplatin might be as effective as cisplatin but has shown to be more tolerable. To further improve treatment options for patients with advanced gastric cancer, we initiated a study to evaluate the efficacy and safety of trastuzumab plus oxaliplatin/capecitabine in patients with HER2-positive advanced gastric cancer. METHODS: CGOG1001 was an open-label, multicenter, prospective phase II study. Patients with chemotherapy-naive HER2-positive advanced gastric cancer were eligible. Trastuzumab was administered at a loading dose of 8 mg/kg followed by 6 mg/kg infusion every 3 weeks (q3w). Oxaliplatin was administrated as a 130 mg/m(2) infusion, q3w, for up to 6 cycles. Capecitabine 1000 mg/m(2) was given orally twice daily on days 1-14 followed by a 7-day rest interval. Trastuzumab and capecitabine were continued until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Simon two-stage design (H0 = 40%, H1 = 60%, α = 0.05, ß = 0.2) by Response Evaluation Criteria In Solid Tumors 1.0 was applied. RESULTS: Fifty-one patients were enrolled. Confirmed response was recorded in 46 patients. One patient achieved complete response and 33 patients achieved partial response (response rate 34/51 [66.7%] in the intent-to-treat population). Median follow-up time was 28.6 months, with a median progression-free survival of 9.2 months (95% confidence interval [CI]: 6.5-11.6) and a median overall survival (OS) of 19.5 months (95% CI: 15.5-26.0). Patients with a HER2/CEP17 ratio of greater than five achieved improved OS (20.9 vs 19.5 months, p = 0.001). The most common adverse events of grade 3 or above were thrombocytopenia (21.6%), neutropenia (13.7%), anemia (5.9 %) and leucopenia (3.9%). CONCLUSION: The addition of trastuzumab to oxaliplatin/capecitabine was well tolerated and the results demonstrated encouraging efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01364493.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/administração & dosagem , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
10.
Anticancer Drugs ; 27(1): 54-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26398932

RESUMO

To investigate the initial symptoms, treatment, prognosis, and 1-, 3-, and 5-year survival of patients with bronchopulmonary carcinoid, clinical and pathological data were collected retrospectively from 74 patients diagnosed with bronchopulmonary neuroendocrine tumors at the Cancer Hospital, Chinese Academy of Medical Science, from January 2004 through December 2009. The data collected included age, initial symptoms, primary tumor sites, pathological types, lymphatic metastasis, and distant metastasis. The Kaplan-Meier method was used for survival analysis and the log-rank test was used for univariate analysis of prognostic factors. A Cox proportional hazard regression model was used for multivariate analysis. The 74 patients included 56 men and 19 women, and their average age was 56.07 years. The most common initial symptom was cough (51.35%), and the major lesion site was the left upper lobe of the lung (38.84%). Of the 59 patients (79.73%) who underwent surgery, most (76.27%) received a pulmonary lobectomy. The patients' 1-, 3-, and 5-year survival rates were 92.7, 80.3, and 71.9%, respectively. Univariate analysis showed that both local lymphatic and distant metastases were prognostic factors (P<0.05), whereas multivariate analysis showed that the pathological type (typical carcinoid and atypical carcinoid) was an independent prognostic factor (P=0.006). These data indicate that cough is the major presenting symptom of patients with bronchopulmonary carcinoid and the left upper lobe of the lung is the most commonly involved site. Following treatment, mostly by pulmonary lobectomy, the 5-year survival rate is 71.9%. The pathological tumor type is an independent prognostic factor.


Assuntos
Neoplasias Brônquicas/diagnóstico , Neoplasias Brônquicas/terapia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Adulto , Idoso , Tumor Carcinoide/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
11.
Gastric Cancer ; 19(1): 234-44, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25604851

RESUMO

BACKGROUND: The V325 study showed that docetaxel, cisplatin, and fluorouracil (DCF) prolonged overall survival (OS) of patients with advanced gastric cancer, but with a high incidence of dose-limiting toxicities. We investigated the efficacy and safety of a modified DCF (mDCF) regimen for Chinese patients with advanced gastric cancer. METHODS: Untreated advanced gastric cancer patients randomly received docetaxel and cisplatin at 60 mg/m(2) (day 1) followed by fluorouracil at 600 mg/m(2)/day (days 1-5; mDCF regimen) or cisplatin at 75 mg/m(2) (day 1) followed by fluorouracil at 600 mg/m(2)/day (days 1-5; CF) every 3 weeks. The primary end point was progression-free survival (PFS). The secondary end points were OS, overall response rate (ORR), time-to-treatment failure (TTF), and safety. RESULTS: In total, 243 patients were randomized to treatment (mDCF regimen 121; CF 122). Compared with CF, the mDCF regimen significantly improved PFS and OS: the median PFS was 7.2 and 4.9 months, respectively [hazard ratio (HR) 0.58, log-rank P = 0.0008], and the median OS was 10.2 and 8.5 months, respectively (HR = 0.71, P = 0.0319). Additionally, the mDCF regimen improved the parameters used as secondary objectives: the ORR was 48.7% with the mDCF regimen versus 33.9% with CF (P = 0.0244); the median TTF was 3.4 months with the mDCF regimen and 2.4 months with CF (HR = 0.67, P = 0.0027). Grade 3 and grade 4 treatment-related adverse events occurred in 77.3 % of patients who received the mDCF regimen versus 46.1% of patients who received CF (P < 0.001). CONCLUSIONS: The mDCF regimen, compared with CF, significantly prolonged PFS and OS and enhanced ORR of Chinese patients with advanced gastric cancer. The mDCF regimen achieved efficacy comparable to that of DCF but with fewer toxicities, which is appropriate for the Chinese population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento , Adulto Jovem
12.
Gastric Cancer ; 18(1): 168-76, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24557418

RESUMO

BACKGROUND: In the AVAGAST study, fluoropyrimidine and cisplatin plus bevacizumab did not significantly improve overall survival (OS) versus fluoropyrimidine and cisplatin plus placebo in patients with advanced gastric cancer. Geographic differences in efficacy were observed in AVAGAST, but the study only included 12 Chinese patients. AVATAR, a study similar in design to AVAGAST, was a randomized, double-blind, phase III study conducted in Chinese patients with advanced gastric cancer. METHODS: Patients more than 18 years of age with gastric adenocarcinoma were randomized 1:1 to capecitabine-cisplatin plus either bevacizumab or placebo. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and safety. RESULTS: In total, 202 patients were included (placebo n = 102; bevacizumab n = 100). Baseline characteristics were well balanced. The primary analysis result did not show a difference in OS for the bevacizumab arm compared to the placebo arm [hazard ratio, 1.11 (95% CI, 0.79-1.56); P = 0.5567]. Median PFS was also similar in both arms. Bevacizumab plus capecitabine-cisplatin was well tolerated. Grade 3-5 adverse events (AEs) occurred in 60% of bevacizumab-treated and 68% of placebo-treated patients, respectively. Grade 3-5 AEs of special interest with bevacizumab occurred in 8% of bevacizumab-treated patients and 15% of placebo-treated patients, mainly grade 3-5 hemorrhage (bevacizumab 4%, placebo 12%). CONCLUSIONS: Addition of bevacizumab to capecitabine-cisplatin in Chinese patients with advanced gastric cancer did not improve outcomes in AVATAR. There was no difference in OS between the two arms and PFS was similar in both arms. Safety findings were as previously experienced with bevacizumab, including AVAGAST; no new safety signals were reported.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Povo Asiático , Bevacizumab , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Método Duplo-Cego , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
13.
World J Surg Oncol ; 13: 190, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-26018798

RESUMO

BACKGROUND: Genitourinary embryonal rhabdomyosarcoma is rarely reported in China. This retrospective analysis aimed to characterize the clinicopathologic features and treatment outcomes of genitourinary embryonal rhabdomyosarcoma in a sample of Chinese patients. METHODS: Basic demographic and clinical data of 29 patients, who were diagnosed with genitourinary embryonal rhabdomyosarcoma between January 2000 and December 2011, were retrieved and analyzed. RESULTS: In these patients, 25 were males and 4 were females with a median age of 12 years. Paratesticule was the most common lesion site, followed by the prostate, bladder, and vagina. The median tumor size was 5.80 cm. Six patients had clinically positive regional nodes. At the initial diagnosis, patients had a metastatic disease. According to the TNM staging classification for the IRS-IV, phase I lesions were detected in ten cases, phase II lesions in six cases, phase III lesions in four cases, and phase IV lesions in nine cases. The median survival of all patients was 63 (range from 6 to 118) months. The 1-, 3-, and 5-year survival rates for these patients were 93%, 83%, and 52%, respectively. Multivariate analyses demonstrated that staging and anemia were significant predictors of prognosis. CONCLUSIONS: Our findings suggest that metastasis predicts a poor prognosis. Chemotherapy played an important role in comprehensive treatment. Palliative and neo-adjuvant chemotherapy could increase median survival time.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rabdomiossarcoma Embrionário/mortalidade , Rabdomiossarcoma Embrionário/patologia , Neoplasias Urogenitais/mortalidade , Neoplasias Urogenitais/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Rabdomiossarcoma Embrionário/tratamento farmacológico , Taxa de Sobrevida , Neoplasias Urogenitais/tratamento farmacológico , Adulto Jovem
14.
Zhonghua Zhong Liu Za Zhi ; 37(8): 622-7, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26714605

RESUMO

OBJECTIVE: To analyze the characteristics of recurrence in gastric cancer patients after radical gastrectomy and adjuvant chemotherapy. METHODS: The clinicopathological data of 110 gastric cancer patients who developed recurrence or second primary malignancies after radical gastrectomy and adjuvant chemotherapy with FOLFOX4 regimen or docetaxel plus FOLFOX4 regimen were analyzed retrospectively. RESULTS: The median time to recurrence was 13.9 months (range, 1.7 to 63.1 months), and the median overall survival was 27.4 months (range, 6.9 to 90.7 months) in the whole group. The median survival time after recurrence was 10.1 months (range, 0.3 to 73.9 months). 82 (74.5%) patients had recurrence within 2 years after gastrectomy. The modes of surgical procedure and lymph node dissection influenced significantly on the time to recurrence (P<0.05 for both). Among the 110 patients with recurrence, 46 (41.8%) patients had peritoneal metastases, 33 (30.0%) had hematogenous metastases and 32 (29.1%) had locoregional lymph node metastases. Single, double, triple and quatro recurrences were observed at the first time of relapse in 78 (70.9%), 21(19.1%), 9(8.2%) and 2 cases (1.8%), respectively. Patients who developed simultaneous quatro recurrence had the poorest prognosis with a median overall survival of 15.2 months, significantly shorter than that of patients with single recurrence (31.8 months, P=0.003). Patients with peritoneal recurrence died most quickly ( mean 5.6 months), and patients with surgical field recurrence alone survived longest (mean 17.1 months). CONCLUSIONS: Peritoneal, hematogenous and locoregional lymph node metastases are the most frequent recurrences after radical gastrectomy and adjuvant chemotherapy in patients with gastric cancer. Single recurrence occurred in most patients at the first relapse. Combination with other adjuvant treatments should be considered besides adjuvant chemotherapy in gastric cancer patients after radical gastrectomy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia/métodos , Recidiva Local de Neoplasia , Neoplasias Gástricas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante , Docetaxel , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Excisão de Linfonodo , Metástase Linfática , Recidiva Local de Neoplasia/mortalidade , Segunda Neoplasia Primária , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxoides/administração & dosagem , Fatores de Tempo
15.
Zhonghua Zhong Liu Za Zhi ; 37(8): 591-6, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26714599

RESUMO

OBJECTIVE: To explore the relationship between DNA mismatch repair (MMR) and clinicopathologic features and prognosis in patients with stages II and III colon cancers. METHODS: The clinical and pathological data of 440 patients with stage II/III colon cancer after radical resection were retrospectively reviewed and analyzed. Immunohistochemical staining was used to assess the expression of MMR proteins (MLH1, MSH2, MSH6 and PMS2), and the correlation between DNA MMR and clinicopathological features and prognosis of colon cancers was analyzed. RESULTS: Of the 440 tumor samples tested for DNA mismatch repair status, 90 (20.5%) demonstrated defective DNA mismatch repair and 350 (79.5%) had proficient DNA mismatch repair. Defective DNA mismatch repair (dMMR) was associated with young patients (≤ 60), proximal colon cancer, stage II, poorly differentiated adenocarcinoma and mucinous adenocarcinoma (P<0.05 for all). Among the 440 patients, 126 (28.6%) cases had recurrence or metastasis and 93 (21.1%) died during the median follow-up of 61.0 months. The five-year disease-free survival (DFS) rate was 82.2% among the patients with tumor exhibiting dMMR, significantly higher than that in patients with tumors exhibiting pMMR (68.9%, P=0.02). The univariate and mutlivariate analyses showed that the MMR status is an independent factor affecting 5-year disease-free survival and overall survival (OS) in colon cancer patients (P<0.05 for both). CONCLUSIONS: Defective DNA mismatch repair (dMMR) is associated with patients with proximal colon cancer, stage II and poorly defferentiated adenocarcinoma and mucinous adenocarcinoma. The prognosis for patients with dMMR is better than those with pMMR. dMMR may be a useful biomarker for the prognosis of colon cancer.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Reparo de Erro de Pareamento de DNA , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenosina Trifosfatases/metabolismo , Fatores Etários , Análise de Variância , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Humanos , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/metabolismo , Recidiva Local de Neoplasia , Proteínas Nucleares/metabolismo , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
16.
Oncologist ; 19(2): 173-4, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24457378

RESUMO

BACKGROUND: The efficacy and toxicity of paclitaxel plus capecitabine (PX) as first-line treatment in advanced gastric cancer (AGC) was evaluated. METHODS: Patients with previously untreated AGC were included. PX was given every 3 weeks until a maximum of six cycles or progression. Capecitabine monotherapy was continued for patients without disease progression. The primary endpoint was progression-free survival, and secondary endpoints were objective response rate, overall survival (OS), and safety. RESULTS: Overall, 194 patients were treated per protocol and one patient was excluded because of allergy to paclitaxel. Response was evaluated in 175 patients, with an objective response rate of 34.8%. After a median follow-up of 33.2 months, disease progression was observed in 141 patients, 137 died, and 16 were lost to follow-up, with progression-free survival of 188 days and OS of 354 days. In multivariate Cox regression analysis, no factor remained an independent predictor of OS. Forty-five patients who received capecitabine monotherapy after PX had longer OS (531 days). Adverse events were mild (Fig. 1), and the most common grade 3-4 toxicities were leucopenia and neutropenia. CONCLUSION: PX as a first-line treatment has promising efficacy in AGC. Based on these data, a phase III study has been launched for further investigation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Masculino , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Prospectivos , Neoplasias Gástricas/patologia , Análise de Sobrevida
17.
J Surg Oncol ; 110(7): 864-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24976079

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) patients with regional lymph node metastases have poor prognosis after surgery. The purpose of this study was to investigate the impact of various treatment modalities on survival in these patients. METHODS: We retrospectively reviewed data from 349 patients who had undergone left transthoracic esophagectomy for thoracic ESCC from January 2008 to December 2010 at our institute. All patients had lesions in the mid or lower third of the thoracic segment and had pathological positive lymph node metastasis. Of these patients, 143 patients received surgery alone, 154 patients underwent postoperative radiotherapy alone, and 52 patients underwent taxane-based chemotherapy. Univariate and multivariate Cox regression analyses were used to analyze prognostic factors and survival. RESULTS: At a median follow-up of 53.1 months, the 3-year OS were 47.7% for the patients with surgery alone, 44.0% for the patients with adjuvant radiotherapy, and 58.9% for the patients with adjuvant chemotherapy. Multivariate analysis showed that postoperative therapy with adjuvant chemotherapy was significant positive predictor of survival. CONCLUSIONS: Postoperative taxane-based adjuvant chemotherapy improved survival of patients with lymph node positive thoracic ESCC compared with surgery alone. Further randomized prospective studies to confirm these findings are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomia , Neoplasias Torácicas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Docetaxel , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem , Neoplasias Torácicas/mortalidade , Neoplasias Torácicas/patologia
18.
Zhonghua Zhong Liu Za Zhi ; 36(3): 212-6, 2014 Mar.
Artigo em Zh | MEDLINE | ID: mdl-24785283

RESUMO

OBJECTIVE: The aim of this study was to analyze the clinical characteristics, treatment and prognosis of advanced urothelial carcinoma of the bladder (AUCB). METHODS: The clinicopathological data of 117 patients with AUCB admitted in our hospital from 1998 to 2009 were reviewed. All patients received first-line chemotherapy. The survival rate was calculated by Kaplan-Meier analysis and log-rank test. RESULTS: The median age of all patients was 56 years and the male-to-female ratio was 3.33:1. Their 6-, 12-, 24-, 36- and 60-month survival rates were 90.3%, 61.3%, 32.3%, 24.2% and 8.1%, respectively. In the first-line chemotherapy regimen, the effectiveness rate of gemcitabine + platinum drugs was 49.3% (37/75), the median progression-free survival(PFS) was 7.9 months and overall survival (OS) was 18.7 months. The effectiveness of cyclophosphamide + epirubicin + platinum drug regimen was 45.5% (10/22), Median PFS was 7.1 months and OS was 15.3 months. The effectiveness of paclitaxel + platinum drug regimen was 47.1% (8/17), median PFS was 6.5 months and OS was 13.7 months. Among them, the effectiveness rate of the gemcitabine + cisplatin regimen in 67 patients was 47.8%, the median PFS was 7.0 months and OS was 15.3 months. In the 13 patients who received paclitaxel + carboplatin regimen, the effectiveness rate was 53.8%, median PFS was 7.7 months and OS was 16.0 months. The major side effects were leucopenia and thrombocytopenia, mostly were tolerable, of grade I to II. CONCLUSIONS: In advanced unresectable and metastatic urothelial carcinoma of the bladder, GC regimen is recognized as a standard first-line chemotherapy, with a higher effectiveness and tolerable side effects. Taxane and molecular targeted drugs may further improve the therapeutic effect of the treatment of advanced urothelial carcinomas of the bladder in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/secundário , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Leucopenia/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Gencitabina
19.
Zhonghua Zhong Liu Za Zhi ; 36(11): 844-8, 2014 Nov.
Artigo em Zh | MEDLINE | ID: mdl-25620482

RESUMO

OBJECTIVE: To investigate the role of DNA mismatch repair (MMR) as a prognostic indicator of radical resection and a predictor of fluorouracil-based adjuvant therapy benefit in patients with stage II/III colon cancer. METHODS: The clinicopathological characteristics of 172 patients with stage II/III colon cancer who underwent radical resection were retrospectively analyzed. Immunohistochemical staining was used to detect the expression of DNA mismatch repair (MLH1/MSH2/MSH6/PMS2) in the tumor tissues. RESULTS: Among a total of 172 patients, there were 38 (22.1%) cases with defective DNA mismatch repair (dMMR) and 134 (77.9%) cases with proficient DNA mismatch repair (pMMR). Among the 115 patients who did not receive adjuvant chemotherapy, those with tumor displaying dMMR had a better 5-year overall survival (OS) rate and disease-free survival (DFS) rate than the patients with proficient DNA mismatch repair (pMMR) (88.0% vs. 66.7%, P = 0.040; 84.0% vs. 60.0%, P = 0.034). The benefit of adjuvant chemotherapy differed significantly according to the MMR status. Adjuvant 5-Fu chemotherapy improved the 5-year overall survival rate among 134 patients with pMMR (86.4%) than that in patients treated by surgery alone (66.7%, P = 0.012). By contrast, there was no benefit of adjuvant 5-Fu chemotherapy in the patients with dMMR (61.5% vs. 86.4%, P = 0.062), which was even more clear the 5-year disease-free survival rate (53.8% vs. 84.0%, P = 0.038). CONCLUSIONS: MMR status is a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II/III colon cancer. Patients with stage II/III colon cancer displaying dMMR have a better prognosis than those with pMMR.


Assuntos
Neoplasias do Colo/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Neoplasias do Colo/terapia , Terapia Combinada , Reparo de Erro de Pareamento de DNA , Intervalo Livre de Doença , Fluoruracila , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Zhonghua Zhong Liu Za Zhi ; 36(5): 346-50, 2014 May.
Artigo em Zh | MEDLINE | ID: mdl-25030589

RESUMO

OBJECTIVE: Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have been reported to be effective in the treatment of esophageal and esophagogastric junction cancers. The aim of this study was to detect the frequency of EGFR mutation and expression in Chinese patients with esophageal, esophagogastric junction and gastric cancers, and to clarify the value of EGFR mutation and expression in predicting the efficacy of TKI in the treatment of these tumors. METHODS: In this study, 180 tumor samples with histologically confirmed esophageal cancer (39 cases), cancer of the esophagogastric junction (92 cases) and gastric cancer (49 cases) were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by real-time PCR-optimized oligonucleotide probe method. EGFR protein expression was evaluated by immunohistochemistry (IHC) in 89 tumor samples. RESULTS: The mutation analysis for EGFR (exons 18-21) showed no mutations in any of the hotspots of the gene in the 180 tumor samples analyzed. EGFR expression was negative in 12 tumor samples, 1+ in 31 tumor samples, 2+ in 24 tumor samples, and 3+ in 22 tumor samples. EGFR expression was 2+ or 3+ in 12 (92.3%) of the 13 esophageal squamous cell carcinomas, 29 (47.5%) of the 61 esophagogastric junction cancers, and 5 (33.3%) of the 15 gastric adenocarcinomas. CONCLUSIONS: Our results indicate that EGFR mutation in exons 18-21 is absent in the examined samples of esophageal, esophagogastric junction and gastric cancers. More studies are warranted to explore the predictive biological markers for the therapeutic response to EGFR TKI.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Neoplasias Esofágicas/genética , Junção Esofagogástrica , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/metabolismo , Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/metabolismo , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/metabolismo , Junção Esofagogástrica/patologia , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Gástricas/metabolismo , Adulto Jovem
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