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1.
Artigo em Inglês | MEDLINE | ID: mdl-31900959

RESUMO

BACKGROUND AND AIM: In the phase 3 CONCUR trial (NCT01584830), regorafenib improved overall survival (OS) versus placebo in Asian patients with treatment-refractory metastatic colorectal cancer (mCRC). We conducted a post hoc subgroup analysis of Chinese patients in CONCUR. METHODS: Adults with mCRC progressing despite at least two prior treatment regimens and Eastern Cooperative Oncology Group performance status 0-1 were randomized 2:1 to regorafenib 160 mg once daily or placebo for the first 3 weeks of each 4-week cycle. Dose modifications were permitted. The primary endpoint was OS. Secondary endpoints included progression-free survival, objective overall response, disease control rate, and safety. RESULTS: A total of 172 Chinese patients were randomized and treated (regorafenib n = 112, placebo n = 60). OS was significantly improved with regorafenib versus placebo (8.4 vs 6.2 months, respectively; hazard ratio [HR] 0.56, 95% CI 0.39-0.80; one-sided P = 0.000632), as was progression-free survival (HR 0.32, 95% CI 0.22-0.47; one-sided P < 0.000001). The most common drug-related grade ≥ 3 treatment-emergent adverse events (TEAEs; regorafenib, placebo) were hand-foot skin reaction (19%, 0%), hypertension (13%, 3%), hypophosphatemia (7%, 0%), increased alanine aminotransferase (6%, 0%), and increased aspartate aminotransferase (5%, 0%). In patients receiving regorafenib and placebo, respectively, TEAEs led to treatment discontinuation in 14% and 7%, dose reduction in 39% and 0%, and dose interruption in 64% and 20%. CONCLUSIONS: This retrospective analysis showed that regorafenib provided an OS benefit over placebo for Chinese patients with previously treated mCRC. TEAEs were consistent with the regorafenib safety profile and manageable with treatment modifications.

2.
Thyroid ; 28(11): 1455-1461, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30142994

RESUMO

BACKGROUND: The prognosis of advanced or metastatic medullary thyroid carcinoma (MTC) is poor, and there are few therapeutic options. Anlotinib has previously shown promising antitumor activity on MTC in preclinical models and a Phase I study. This Phase II clinical trial was devised to confirm the antitumor activity of anlotinib in patients with advanced or metastatic MTC. METHODS: Patients with unresectable locally advanced or metastatic MTC received once daily oral anlotinib 12 mg, two weeks on/one week off, until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reason. The dose was adjusted on the basis of observed toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Fifty-eight patients received anlotinib treatment. The primary endpoint PFS has not yet been reached at the time of analysis. On the basis of investigator assessments, 56.9% of patients experienced a partial response. PFS rate at 48 weeks was 85.5%. Forty-five patients had a ≥50% decrease in serum calcitonin concentration from baseline. The most common adverse events were hand-foot syndrome, hypertriglyceridemia, cholesterol elevation, fatigue, and proteinuria. CONCLUSIONS: Anlotinib demonstrated a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic MTC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Medular/tratamento farmacológico , Indóis/uso terapêutico , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Calcitonina/sangue , Carcinoma Medular/sangue , Carcinoma Medular/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Adulto Jovem
3.
Zhonghua Zhong Liu Za Zhi ; 40(8): 631-635, 2018 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-30139036

RESUMO

Objective: To assess the clinicopathological feature and prognosis of gastric cancer associated with pregnancy in Chinese population. Methods: We collected the clinical features, pathological findings, treatment modalities, the health status of infants and the information of prognosis for ten patients developed gastric cancer associated with pregnancy between 2001 and 2016 in our hospital and the counterpart 12 patients reported in China National Knowledge Internet (CNKI), Wanfang database and China Science and Technology Journal Database. Results: The most common symptoms were nausea and vomiting (n=14). Melena (n=8), abdominal distension (n=7) and abdominal pain (n=6) were also frequent. When considering the complications, gastrointestinal bleeding (n=9), intestinal obstruction (n=3) and gastric perforation (n=2) were common. The vast majority of pathology showed poorly differentiated tumors, poorly differentiated adenocarcinoma (n=14) and signet ring cell carcinoma (n=7). Only one patient was diagnosed at stage Ⅰ. And 17 patients developed metastatic disease of stage Ⅳ. Peritoneum (n=7) and ovary (n=5) were the most common metastasis sites. Three patients received abortion immediately after diagnosis in the first trimester of pregnancy. For the five patients in the second trimester of pregnancy, pregnancy termination was given to three patients. Caesarean section followed by gastrectomy was performed on three patients who were after the third trimester of gestation. Curative resection and palliative operation were carried out on six and five patients respectively. Combined chemotherapy based on oxaliplatin and fluorouracil was the common treatment for the peri-operative patients. For the metastatic gastric caner, platinum in combination with fluorouracil was recommended in the first line condition, irinotecan or raltitrexed were used in the second line treatment. One-year survival rate was 23.1%, and two-years survival was 15.4%. Three patients after R0 resection were alive without relapse over 18 months. Conclusions: The poor prognosis of gastric cancer associated with pregnancy may due to the late stage and the poor pathological type. There still lacks data of the appropriate treatment in these patients. It was demonstrated most patients have no chance of tumor resection due to the late stage. For the metastatic patients, platinum in combination with fluorouracil was recommended in the first line treatment. Irinotecan or raltitrexed were considered the choice for the second line treatment.


Assuntos
Adenocarcinoma/complicações , Carcinoma de Células em Anel de Sinete/complicações , Complicações Neoplásicas na Gravidez , Neoplasias Gástricas/complicações , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/secundário , Carcinoma de Células em Anel de Sinete/terapia , Cesárea , China , Feminino , Fluoruracila/administração & dosagem , Gastrectomia , Humanos , Irinotecano , Recidiva Local de Neoplasia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Cuidados Paliativos , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Prognóstico , Quinazolinas/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Taxa de Sobrevida , Tiofenos/administração & dosagem
4.
BMC Cancer ; 18(1): 803, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30089457

RESUMO

BACKGROUND: Previous studies have reported that neoadjuvant chemoradiotherapy can downstage the advanced gastric cancer. However, no studies are available on the application of hypo-radiotherapy to neoadjuvant radiotherapy. This study sought to assess the maximum tolerated dose (MTD) and dose-limited toxicity (DLT) of hypo-fractionated chemoradiotherapy for local advanced gastric cancer. METHOD: Patients with cT3-4 and/or lymph node-positive locally advanced gastric cancer or Siewert II/III esophagogastric junction adenocarcinoma were enrolled. Preoperative chemoradiation was followed by 3 cycles of oxaliplatin + S-1 neoadjuvant chemotherapy with an interval duration of 3-4 weeks. D2 resection was performed 2-4 weeks after neoadjuvant therapy. Three cycles of adjuvant chemotherapy were planned after surgery. Intensity-modulated radiotherapy (IMRT) was used. The radiotherapy dose level was defined using three levels, namely, 40.0 Gy/2.5 Gy, 41.6 Gy/2.6 Gy, 43.2 Gy/2.7 Gy delivered concurrently with S-1 at 80 mg/m2. RESULTS: From May 2016 to Dec 2016, nine patients with a median age of 63 years were enrolled in this study. The most common grade I-III adverse events were leukopenia (88.9%), nausea (88.9%), vomiting (77.8%) and weight loss (66.7%). Grade III adverse events consisted of vomiting and weight loss. CONCLUSION: The MTD of hypo-fractionated radiotherapy for locally advanced gastric cancer was 40.0 Gy/2.5 Gy, and the DLTs were vomiting and weight loss. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03427684 (Retrospectively registered on February 9, 2018).


Assuntos
Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Hipofracionamento da Dose de Radiação , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
5.
Clin Cancer Res ; 24(21): 5233-5238, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29895706

RESUMO

Purpose: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies.Patients and Methods: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR12 weeks).Results: A total of 166 patients were included in the final analysis. Overall, the PFR12 weeks was 68%, and objective response rate was 13% (95% confidence interval, 7.6%-18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR12 weeks, median PFS and OS were: 58%, 4.1 and 11 months for UPS (n = 19); 63%, 5.6 and 13 months for LPS (n = 13); 75%, 11 and 15 months for LMS (n = 26); 75%, 7.7 and 12 months for SS (n = 47); 81%, 5.6 and 12 months for FS (n = 18); 77%, 21 and not reached for ASPS (n = 13); 54%, 11 and 16 months for CCS (n = 7); and 44%, 2.8 and 8.8 months for other sarcoma (n = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred.Conclusions: Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. Clin Cancer Res; 24(21); 5233-8. ©2018 AACR.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Indóis/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/patologia , Adolescente , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Animais , Terapia Combinada , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/mortalidade , Resultado do Tratamento , Adulto Jovem
6.
Br J Cancer ; 119(5): 538-545, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29755117

RESUMO

BACKGROUND: To assess the safety profile, pharmacokinetics, pharmacodynamics and preliminary antitumour activity of fixed-dose SHR-1210, a novel anti-PD-1 antibody, in advanced solid tumours. METHODS: A total of 36 patients with advanced solid tumours received intravenous SHR-1210 at 60 mg, 200 mg and 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. The concentration of SHR-1210 was detected for pharmacokinetics, and receptor occupancy on circulating T lymphocytes was assessed for pharmacodynamics. RESULTS: No dose-limiting toxicities were observed. Maximum administered dose was not reached. Most adverse events were grade 1 or 2. Treatment-related severe adverse events were found in two patients. No treatment-related death was reported. Two complete responses (gastric cancer, bladder carcinoma) and seven partial responses were seen. In responders, the median follow-up time was 16.0 months (range 8.3-19.5), and the median duration of response was not reached (range 2.7-17.5+ months). The half-life of SHR-1210 was 2.94 d, 5.61 d and 11.0 d for 3 dose levels, respectively. CONCLUSIONS: Our results demonstrated a promising antitumour activity and a manageable safety profile of SHR-1210, displayed an explicit PK evidence of the feasibility of fixed dose, and established the foundation for further exploration.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Neoplasias/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento
7.
Neuroendocrinology ; 106(4): 318-323, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28817826

RESUMO

PURPOSE: Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1/temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. METHODS: A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75.00%) had failed 1 or more lines of treatment with somatostatin analogues, sunitinib, everolimus, anlotinib, or other chemotherapy regimens. The patients received S-1 at 40 mg/m2 orally twice daily on days 1-14 and temozolomide 200 mg orally once daily on days 10-14 of a 21-day cycle. The patients were followed up for evidence of object response, toxicity, and progression-free survival. RESULTS: Response to treatment was assessed using RECIST 1.1. Eight patients (40.00%) achieved a partial response (PR), and another 8 (40.00%) had stable disease (SD). The clinical benefit rate (PR and SD) was 80.00%. The median progression-free survival was not achieved. Only 1 patient (5.00%) had grade 3 adverse events. Among the patients with NETs of different origins, 4 (40.00%) and 5 (50.00%) with pancreatic NETs attained PR and SD, respectively. Four (40.00%) and 3 patients (30.00%) with nonpancreatic NETs attained PR and SD, respectively. CONCLUSIONS: The STEM regimen is exceptionally highly active and well tolerated in patients with locally advanced or metastatic NETs. Even in patients who showed disease progression with previous therapies, it is still highly active. In this 20-patient study, the regimen appeared to be similarly active in pancreatic endocrine tumors and nonpancreatic NETs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Adulto , Idoso , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Estudos Retrospectivos , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Temozolomida/administração & dosagem , Temozolomida/efeitos adversos , Resultado do Tratamento
8.
Oncotarget ; 8(42): 71699-71708, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-29069739

RESUMO

BACKGROUND: Representative data on the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in Asian patients is rare, especially in China. This study aims to create a GEP-NENs profile of Chinese patients. METHODS: This was a hospital-based, nation-wide, and multi-center 10-year (2001-2010) retrospective study which collected GEP-NEN patients' information in tertiary referral hospitals. All 2010 inpatient GEP-NEN cases with confirmed pathology in the selected hospitals were included. The primary GEP-NEN sites were measured and the epidemiological and clinical information of each tumor site were compared. RESULTS: The most common primary sites for GEP-NEN were the pancreas (31.5%) and rectum (29.6%), followed by the cardia (11.6%) and body (15.4%) of stomach. Small intestinal and colonic NENs took up a relatively small proportion of all patients. Pancreatic and rectal NENs, rather than cardiac and gastric body NENs, tended to be found in younger (P<0.001), female (P<0.001), urban (P<0.001) residents with a higher education level (P=0.032) and were also diagnosed at earlier stage (P<0.001) and lower grade (P<0.001). Surgery remained the primary treatment method in all groups. CONCLUSIONS: More studies on the commonality and heterogeneity of GEP-NENs are warranted to improve diagnosis efficiencies and treatment outcomes.

9.
Int J Oncol ; 49(5): 1991-2000, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27826620

RESUMO

Pancreatic neuroendocrine neoplasms (p-NENs) are slowly growing tumors with frequent liver metastasis. There is a variety of approaches to treat non-functional p-NENs with synchronous liver metastasis (LM) which complicates the determination of optimal treatment. Based on updated literature review, we discussed the treatment strategy determinants for p-NEN with LM. According to the resectability of primary tumor, the WHO 2010 grade classification and the radiological type of liver metastasis, the CSNET group reached agreements on a number of issues, including the following. Prior to treatment, biopsy is required to confirm pathology. Liver biopsy is important for more accurate grading of tumor and percutaneous core needle biopsy is more available than EUS-FNA. In patients with unresectable primary, surgical resection for liver-metastatic lesions should be avoided. Curative surgery is recommended for G1/G2 p-NET with type I LM and R1 resection also seems to improve overall survival rate. Cytoreductive surgery is recommended for G1/G2 p-NET with type II LM in select patients, and should meet stated requirements. Surgical resection for G1/G2 p-NET with type III LM and p-NEC with LM should be avoided, and insufficient evidence exists to guide the surgical treatment of G3 p-NET with LM. Liver transplantation may be an option in highly select patients. In addition, the optimal time for surgical approach is still required for more evidence.


Assuntos
Neoplasias Hepáticas/cirurgia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Guias de Prática Clínica como Assunto/normas , China , Consenso , Humanos , Neoplasias Hepáticas/secundário , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Taxa de Sobrevida , Resultado do Tratamento
10.
J Hematol Oncol ; 9(1): 105, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27716285

RESUMO

BACKGROUND: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/ß, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. METHODS: Anlotinib (5-16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1). Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. RESULTS: On the 4/0 schedule, dose-limiting toxicity (DLT) was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma) were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. CONCLUSIONS: At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.


Assuntos
Indóis/administração & dosagem , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Quinolinas/administração & dosagem , Terapia de Salvação/métodos , Adulto , Idoso , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Neoplasias/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/farmacologia , Terapia de Salvação/efeitos adversos , Resultado do Tratamento , Adulto Jovem
11.
Zhonghua Zhong Liu Za Zhi ; 38(9): 698-702, 2016 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-27647404

RESUMO

OBJECTIVE: Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) are widely used for the treatment of metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the association between treatment-related hypertension and the therapeutic efficacy of VEGFR-TKIs. METHODS: Clinical data of 155 mRCC patients treated with VEGFR-TKIs at the Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were retrospectively analyzed. All patients received first-line TKI therapy. Among them, 69 patients were treated with sunitinib, 14 cases with pazopanib, and 51 cases with fazotinib. Kaplan-Meier curves were used to evaluate the survival of the patients. RESULTS: The median survival for the whole group (n=155) was 36.2 months. Among the 98 (63.2%) patients who developed hypertension, 9 patients (5.8%) were evaluated as grade Ⅰ, 54 (34.8%) as grade Ⅱ and 35 (22.6%) as grade Ⅲ, and there was no patient with grade Ⅳ hypertension. The occurrence of TKI-related hypertension was correlated with age and MSKCC score (P<0.05), while not significantly correlated with gender, nephrectomy, T stage, number of metastases, lung metastasis or sunitinib treatment (P>0.05 for all). For the whole group (n=155), the therapeutic efficacy rate was 43.2% (67/155), the median progression-free survival (PFS) was 12.0 months, and the median overall survival (OS) was 36.2 months. The response rate (RR) was 26.3% (15/57) in patients with normal blood pressure and 53.1% (52/98) in patients with hypertension (P=0.001). The median PFS was 7.1 months in the cases with normal blood pressure and 13.8 months in patients with hypertension (P=0.032). The response rates were 33.3% (3/9), 51.9% (28/54) and 60.0% (21/35) in patients with grade Ⅰ, Ⅱ and Ⅲ hypertension (P=0.006). The median PFS was 7.1, 9.7, and 12.0 and 19.5 months in patients with normal blood pressure, and patients with grade Ⅰ, Ⅱ and Ⅲ hypertension, respectively (P=0.039). Both univariant and multivariant analyses indicated that treatment-related hypertension is an important predictive factor for the efficacy of VEGFR-TKIs therapy. CONCLUSIONS: Hypertension might be an effective predictive factor for efficacy of VEGFR-TKIs therapy in mRCC patients. Large-sample studies are warranted to further prove these results.


Assuntos
Carcinoma de Células Renais , Hipertensão , Neoplasias Renais , Intervalo Livre de Doença , Feminino , Humanos , Indóis , Masculino , Metástase Neoplásica , Nefrectomia , Inibidores de Proteínas Quinases , Pirimidinas , Pirróis , Estudos Retrospectivos , Sulfonamidas , Sunitinibe , Fator A de Crescimento do Endotélio Vascular
12.
Medicine (Baltimore) ; 95(18): e3567, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27149478

RESUMO

Gastrin-independent gastric neuroendocrine tumors (GNETs) are highly malignant. Radical resections and lymphadenectomy are considered to be the only possible curative treatment for these tumors. However, the prognosis of gastrin-independent GNETs is not well defined. In this study, we identified prognostic factors of locoregional gastrin-independent GNETs.All patients diagnosed with locoregional gastrin-independent GNETs between 2000 and 2014 were included in this retrospective study. Clinical characteristics, blood tests, pathological characteristics, treatments, and follow-up data of the patients were collected and analyzed.Of the 66 patients diagnosed with locoregional gastrin-independent GNETs, 57 (86.4%) received radical resections, 7 (10.6%) with palliative resection, 1 (1.5%) with gastrojejunostomy, and 1 (1.5%) with exploration surgeries. The median survival time for these patients was 19.0 months (interquartile range, 11.0-38.0). The 1-, 3-, and 5-year survival rates were 72%, 34%, and 28%, respectively. Multivariate analysis indicated that carcinoembryonic antigen (CEA) level (P = 0.04), radical resection (P = 0.04), and positive Cluster of Differentiation 56 (CD56) expression (P = 0.016) were significant prognostic factors on overall survival rate. Further univariate and multivariate analysis of 57 patients who received radical resections found that CgA expression (P = 0.35) and CEA level (P = 0.33) are independent prognostic factors.Gastrin-independent GNETs had poor prognosis. Serum CEA level, radical surgery, CD56 and CgA expression are markers to evaluate the survival of patients with locoregional gastrin-independent GNETs.


Assuntos
Antígeno CD56/sangue , Antígeno Carcinoembrionário/sangue , Cromogranina A/sangue , Tumores Neuroendócrinos/diagnóstico , Neoplasias Gástricas/diagnóstico , Feminino , Gastrectomia , Gastrinas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
13.
Asia Pac J Clin Oncol ; 12(2): 174-80, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26997520

RESUMO

AIM: Vascular endothelial growth facto receptor-tyrosine kinase inhibitors (VEGFR-TKIs) are widely used for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the association between the response to VEGFR-TKIs and hyperlipidemia and hypothyroidism. METHODS: Clinical data on 155 patients with mRCC treated with VEGFR-TKIs at the Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were retrospectively analyzed. All patients received first-line TKI therapy. Survival analysis was performed with a significance level of 0.05 using a Kaplan-Meier curve. The χ(2) test was used for the intergroup comparison. The Cox regression model was used for the analysis of multiple factors affecting survival. RESULTS: The median survival for the whole group (n = 155) was 36.2 months. A total of 57 patients (36.8 percent) developed hypothyroidism and 85 patients (54.9 percent) experienced hyperlipidemia. The response rate (RR) and median progression-free survival (mPFS) for patients with normal thyroid function were 32.7 percent and 9.1 months, respectively, 54.5 percent and 13.7 months with grade I hypothyroidism, 70.8 percent and 23.8 months with grade II hypothyroidism (P values of 0.001 and 0.017, respectively). The RR and mPFS for patients with normal blood lipids were 23.9 percent and 8.0 months, respectively, 54.0 percent and 12.9 months with grade I hyperlipidemia, 60.7 percent and 14.0 months with grade II hyperlipidemia, and 100.0 percent and 22.2 months with grade III hyperlipidemia. Significant differences in the RR and mPFS were seen between groups (the P values were 0.000 and 0.005, respectively). CONCLUSION: Hypothyroidism or hyperlipidemia may be effective predictive factors for response to treatment with VEGFR-TKIs in mRCC patients. Large-sample studies are warranted to further prove these results.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Hiperlipidemias/enzimologia , Hipotireoidismo/enzimologia , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/enzimologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/enzimologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
14.
Chin Med J (Engl) ; 129(5): 530-5, 2016 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-26904986

RESUMO

BACKGROUND: The metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with α-interferon yields additional overall survival (OS) benefits. It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) will benefit from such cytoreductive nephrectomy either. The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR-TKI. METHODS: Clinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital (Institute), Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively. The survival analysis was performed by the Kaplan-Meier method. Comparisons between patient groups were performed by Chi-square test. A Cox regression model was adopted for analysis of multiple factors affecting survival, with a significance level of α = 0.05. RESULTS: Fifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 23 patients were treated with targeted therapy alone (noncytoreductive nephrectomy group). The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups, respectively (P = 0.041). Age ≤45 years (P = 0.002), a low or high body mass index (BMI <19 or >30 kg/m2) (P = 0.008), a serum lactate dehydrogenase (LDH) concentration >1.5 × upper limit of normal (P = 0.025), a serum calcium concentration >10 mg/ml (P = 0.034), and 3 or more metastatic sites (P = 0.023) were independent preoperative risk factors for survival. The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone (40.0 months vs. 23.2 months, P = 0.042), while those with more than 2 risk factors did not. CONCLUSIONS: Five risk factors (age, BMI, LDH, serum calcium, and number of metastatic sites) seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy.


Assuntos
Carcinoma de Células Renais/cirurgia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Renais/cirurgia , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais
15.
Medicine (Baltimore) ; 95(7): e2836, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26886644

RESUMO

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria. This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based on WHO/ENETS criteria. The clinicopathological features of PNETs of Chinese and US patients were compared. Univariate and multivariate analyses were performed to find associations between survival and patient demographics, tumor grade and stage, and other clinicopathological characteristics. A total of 977 (527 Chinese and 450 US) patients with PNETs were studied. In general, Chinese patients were younger than US patients (median age 46 vs 56 years). In Chinese patients, insulinomas were the most common (52.2%), followed by nonfunctional tumors (39.7%), whereas the order was reversed in US patients. Tumor grade distribution was similar in the 2 countries (G1: 57.5% vs 55.0%; G2: 38.5% vs 41.3%; and G3: 4.0% vs 3.7%). However, age, primary tumor size, primary tumor location, grade, and stage of subtypes of PNETs were significantly different between the 2 countries. The Chinese nonfunctional tumors were significantly larger than US ones (median size 4 vs 3 cm) and more frequently located in the head/neck region (54.9% vs 34.8%). The Chinese and US insulinomas were similar in size (median 1.5 cm) but the Chinese insulinomas relatively more frequently located in the head/neck region (48.3% vs 26.1%). Higher grade, advanced stage, metastasis, and larger primary tumor size were significantly associated with unfavorable survival in both countries. Several clinicopathological differences are found between Chinese and US PNETs but the PNETs of both countries follow a similar natural history. The WHO tumor grading and ENETS staging criteria are applicable to both Chinese and US patients.


Assuntos
Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Prognóstico , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
16.
Urol Oncol ; 34(6): 258.e15-22, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26803435

RESUMO

PURPOSE: Tyrosine kinase inhibitors (TKIs) are the preferred treatment drugs for metastatic renal cell carcinoma (mRCC). The aim of this study was to analyze prognostic factors for overall survival (OS) in patients with mRCC treated with TKIs. MATERIALS AND METHODS: Clinical data on 155 patients enrolled in 5 clinical trials conducted at our hospital from 2006 to 2014 were reviewed retrospectively. All patients received first-line TKI therapy (sunitinib, sorafenib, pazopanib, or famitinib). Survival rates were determined by the Kaplan-Meier method. RESULTS: Median OS (mOS) was 36.2 months. A total of 4 of the 5 adverse prognostic factors identified by the Memorial Sloan-Kettering Cancer Center (MSKCC) were found to be independent predictors of shorter survival, anemia, hypercalcemia, lactate dehydrogenase>1.5×upper limit of normal, and diagnosis to treatment time<1 year. In addition, we found that age≤45 years (P = 0.002), low or high body mass index ([BMI]<19 or>30kg/m(2)) (P = 0.003), and presence of≥3 metastatic sites (P = 0.000) were also independent adverse prognostic factors. According to the MSKCC model, the mOS time in the favorable-risk, intermediate-risk, and poor-risk groups were 46.6, 30.4 and 16.7 months, respectively (P = 0.005). When we integrated age and BMI into the MSKCC model to set up a 7-factor prognostic model, we found the mOS time for these 3 groups was 71.1, 41.6 and 15.3 months, respectively (P = 0.000). CONCLUSION: Age and BMI are additional independent prognostic factors for patients with mRCC receiving vascular endothelial growth factor receptor-targeted TKI treatment, and the MSKCC prognostic model is also applicable to them. A 7-factor prognostic model might help to identify patients with the best prognosis. Further studies are needed to confirm these findings.


Assuntos
Fatores Etários , Índice de Massa Corporal , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidores
17.
Artigo em Inglês | MEDLINE | ID: mdl-28138614

RESUMO

Pancreatic neuroendocrine tumor (pNET) is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. Except insulinoma, majority of pNET are metastatic when diagnosis. And liver is the most common organ of distant metastases. Liver metastases are the main determinant for long-term survival and quality of life of patients with pNET. A case of liver metastases of pNET of a 44-year-old female patient is presented in this study. Then we have a brief discussion of the diagnosis and multidisciplinary treatment of advanced pNET.

18.
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
19.
Chin Med J (Engl) ; 128(23): 3149-52, 2015 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-26612287

RESUMO

BACKGROUND: Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair (MMR) status may relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognosis. METHODS: The medical records of 11,503 patients diagnosed as colorectal cancer in Cancer Hospital, Chinese Academy of Medical Sciences from January 1999 to December 2009 were retrospectively reviewed. Finally, 19 patients who were between 10 and 20 years old were selected as the study group. We summarized the clinicopathological characteristics, analyzed the association with prognosis and assessed the expression of MMR protein by immunohistochemical method. RESULTS: The most common primary site was the right colon in 7 patients. Ten patients had Stage III colorectal cancer, 5 patients had Stage IV disease. Signet ring cell carcinoma was the most frequent pathological type (7/19). Deficient MMR was identified in 2 patients. The 5-year survival rate and median survival time were 23.2% and 26 months. Distant metastasis was identified as an independent prognostic factor (P = 0.02). CONCLUSIONS: Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage III/IV disease with signet ring cell carcinoma. The prognosis was relatively poor.


Assuntos
Neoplasias Colorretais/patologia , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , Criança , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Reparo de Erro de Pareamento de DNA/genética , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Chin J Cancer Res ; 27(3): 239-46, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26157320

RESUMO

OBJECTIVE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. METHODS: According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. RESULTS: In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. CONCLUSIONS: Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

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