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1.
Nihon Shokakibyo Gakkai Zasshi ; 117(2): 150-156, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32037360

RESUMO

New chemotherapeutic regimens such as S-1 plus docetaxel, S-1 plus oxaliplatin and capecitabine plus oxaliplatin are reported to be effective and safe as postoperative adjuvant chemotherapy (PAC) for advanced gastric cancer (GC) patients. Although the use of these PACs is increasing, it is still unclear how to choose the best regimen for advanced GC patients. Therefore, we aimed to investigate which clinical characteristics are associated with recurrence after curative surgery in patients receiving S-1 as PAC. Thirty-nine patients who received a PAC regimen with S-1 for more than 1 year after curative surgery for advanced GC were enrolled. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with recurrence. Patients were divided into two groups, recurrence, and non-recurrence, and receiver operating characteristic (ROC) curve analysis was used to identify the cut-off values. Kaplan-Meier analysis and the log-rank test were used for comparison of relapse-free survival (RFS). Fifteen patients had a recurrence after surgery (38.5%, 15/39). Multivariate analysis using clinical characteristics revealed that preoperative C-reactive protein (CRP) (>0.3/≤0.3, mg/dL) (HR 10.73;95% C.I., 1.824-63.14;P=0.009) was significantly associated with recurrence. Kaplan-Meier analysis and the log-rank test demonstrated that preoperative CRP (>0.3/≤0.3, mg/dL) was also significantly associated with RFS (P<0.001). Therefore, preoperative CRP is significantly associated with recurrence and RFS after curative surgery in advanced GC patients receiving S-1 as PAC.


Assuntos
Proteína C-Reativa/metabolismo , Quimioterapia Adjuvante/métodos , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 99(3): e18892, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011517

RESUMO

RATIONALE: Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before. PATIENT CONCERNS: A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis. DIAGNOSES: Primary SCCE (pT1bN1M0, IIB) was established after salvage operation. INTERVENTIONS: The tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic. OUTCOMES: The adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019. LESSONS: S-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Tegafur/uso terapêutico , Carcinoma de Células Pequenas/cirurgia , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Irinotecano/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Salvação
3.
Anticancer Res ; 39(12): 6567-6573, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810922

RESUMO

BACKGROUND/AIM: The KIAA1199 gene has been associated with cancer-cell proliferation, but its functions remain poorly studied. Here, we examined the clinical significance of the KIAA1199 mRNA levels in locally advanced gastric cancer (GC). Materials and Methods/Results: Using samples from 254 patients with stage II/III GC, we found significantly higher KIAA1199 levels in cancerous tissues compared to adjacent normal mucosa (ANM). There was no significant relationship between KIAA1199 expression and clinical features. Although overall survival rates (OSR) of patients, who underwent surgery did not correlate with KIAA1199 expression, patients who underwent adjuvant chemotherapy with S-1 and had high KIAA1199 levels displayed significantly lower OSR. KIAA1199 knock down (KIAA1199-KD) suppressed proliferation, invasiveness, and sensitivity of GC cells to 5-fluorouracil (5-FU). CONCLUSION: KIAA1199 expression appears to be a promising prognostic marker in patients with locally advanced GC, who underwent postoperative adjuvant chemotherapy with S-1. KIAA1199 may represent a novel target for GC pharmacotherapy.


Assuntos
Hialuronoglucosaminidase/genética , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/terapia , Tegafur/uso terapêutico , Regulação para Cima , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Quimioterapia Adjuvante , Procedimentos Cirúrgicos do Sistema Digestório , Combinação de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
5.
Medicine (Baltimore) ; 98(44): e17605, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689766

RESUMO

Some postoperative gastric cancer patients have to terminate systemic intravenous chemotherapy early due to adverse drug reactions. We performed a retrospective study to explore the efficacy and feasibility of sequential therapy.We retrospectively analyzed 55 postoperative gastric cancer patients (Group A) who received sequential therapy (intravenous chemotherapy and S-1) and 53 patients (Group B) who received intravenous chemotherapy from January 2012 to December 2013 in our hospital. The therapeutic effect (including 1-year, 5-year tumor recurrence and survival rate) and the incidence of adverse reactions were analyzed.When death and survival for more than 5 years was regarded as the end point of follow-up, the mean follow-up period was 40.6 months (34.7-46.4) in Group A and 39.2 months (33.0-45.3) in Group B. The 1-year tumor recurrence after the operation was 23.6% (13/55, Group A) and 28.3% (15/53, Group B). The 5-year tumor recurrence was 45.5% (25/55, Group A) and 49.1% (26/53, Group B). There was no significant difference in the 1- and 5-year tumor recurrence rates between these two groups (P > .05). The 1-year survival rates of Group A and Group B were 81.8% (45/55) and 79.2% (42/53), respectively, and the 5-year survival rates of Group A and Group B were 47.3% (26/55) and 45.3% (24/53), respectively. No significant difference was observed between these two treatments at either the 1- or 5-year survival benefit (P > .05). However, the patients in Group A had a lower incidence of gastrointestinal reactions (such as nausea and vomiting), leukopenia and liver function damage (P < .05). We also found that patients who underwent sequential therapy might show lower levels of adverse reactions.Our retrospective study provided some evidence to suggest that sequential treatment is effective and safe for postoperative gastric cancer patients who are intolerant to intravenous chemotherapy.


Assuntos
Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico , Administração Oral , Adulto , Idoso , Quimioterapia Adjuvante , Combinação de Medicamentos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos
6.
Gan To Kagaku Ryoho ; 46(11): 1753-1755, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31748486

RESUMO

A 79-year-old woman had recurrence in the mediastinal lymph node 6 months after curative resection of advanced esophageal cancer(pStage Ⅲ). After radiation therapy and 12 courses of chemotherapy with docetaxel, new recurrent tumors progressed in the mediastinum and apical region of the left lung, and her performance status(PS)deteriorated to grade 3. Alternate-day, low-dose S-1 chemotherapy was started at a dose of 60mg/day. Tumors decreased in size within 6 months, and her PS improved from grade 3 to 0. She had been treated for 33 months without severe adverse events until disease progression. So far, we have experienced in clinical practices that the alternate-day S-1 administration was tolerable for patients who were unfit for the standard daily administration. Alternate-day, low-dose S-1 administration may be a sustainable and effective option in S-1 chemotherapy in patients with recurrent esophageal cancer with impaired PS.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Esofágicas , Recidiva Local de Neoplasia , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Docetaxel , Combinação de Medicamentos , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Humanos , Linfonodos , Mediastino
7.
Anticancer Res ; 39(10): 5565-5572, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570451

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate the status of extravasated platelet activation (EPA) surrounding podoplanin (PDPN)-positive cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma by neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 74 patients were enrolled in this study. We investigated CD42b and PDPN expression in the groups of untreated, gemcitabine (GEM) alone, GEM plus S-1 (GS) and GEM plus nab-paclitaxel (GnP). RESULTS: CD42b expression in surrounding CAFs was observed in 58% patients. CD42b expression was significantly correlated with PDPN expression. CD42b-positive cases were significantly lower in the group treated with GnP than in the untreated group and groups treated with GEM alone or GS. PDPN expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of PDPN-positive fibroblasts. There was a significantly lower CD42b expression and fewer PDPN-positive fibroblasts in the GnP group than in untreated, GEM alone, and GS groups, but there was no significant difference between the latter three groups. CONCLUSION: There is a significant association between EPA and PDPN-positive CAFs in pancreatic cancer stroma. Our data suggest that the GnP regimen decreases EPA through PDPN-positive CAF depletion.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibroblastos Associados a Câncer/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/uso terapêutico , Fibroblastos Associados a Câncer/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Ácido Oxônico/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Tegafur/uso terapêutico
8.
Gan To Kagaku Ryoho ; 46(10): 1573-1575, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631142

RESUMO

After undergoing an upper gastrointestinal endoscopy, a 74-year-old woman with anemia was diagnosed with advanced lower gastric cancer. We performed laparotomy and identified the tumor as unresectable because of the direct invasion to the pancreas. S-1 was administered at 60mg/day for 2 weeks followed by 1-week discontinuation. After 6 weeks, we changed the schedule to the same dosage of S-1 for 1 week followed by 2-week discontinuation. CT and endoscopic findings showed complete response after 64weeks of S-1 administration. Since then, S-1 has been maintained at 60mg/day intermittently for 14 days in 7 weeks accordingto the patient's condition. The patient is currently doingwell with a complete response for more than 5 years.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas , Tegafur/uso terapêutico , Idoso , Combinação de Medicamentos , Feminino , Humanos , Indução de Remissão , Neoplasias Gástricas/tratamento farmacológico
9.
BMC Cancer ; 19(1): 962, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619197

RESUMO

BACKGROUND: We previously reported the synergistic effect of S-1 and eribulin in preclinical models. In addition, our phase I study revealed the recommended dose for the phase II study of the combination therapy in advanced breast cancer (ABC) patients pre-treated with anthracycline and taxane. Our current study reports on the efficacy and safety of the combined use of eribulin and S-1 in patients with ABC and poor prognosis. METHODS: Patients with breast cancer who received prior anthracycline- and/or taxane-based therapy were assigned to receive a combination therapy of eribulin (1.4 mg/m2 on days 1 and 8, every 21 days) and S-1 (65 mg/m2, on days 1 to 14, every 21 days) for advanced/metastatic disease. All patients had at least one clinicopathological factor such as being oestrogen receptor negative, Human Epidermal Growth Factor Receptor 2 (HER2) receptor negative, presence of visceral involvement, presence of three or more metastatic sites, or having a disease-free interval shorter than 2 years. The primary endpoint was the independent-reviewer assessed objective response rate (ORR). Secondary endpoints were clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival (OS). RESULTS: This study enrolled 33 patients. Confirmed ORR was 33.3% (95% CI: 17.3 to 52.8). Median PFS was 7.5 months (95% CI: 4.0 to 14.3). Median OS time was not reached during the current experimental periods. The most common grade 3/4 adverse event was neutropenia (68.8%). CONCLUSIONS: The combination of eribulin and S-1 is safe and effective for treatment in patients with ABC and poor prognosis. TRIAL REGISTRATION: Current Controlled Trials UMIN000015049 , date of registration: September 5th 2014.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Adulto , Idoso , Antraciclinas/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Furanos/administração & dosagem , Furanos/efeitos adversos , Humanos , Cetonas/administração & dosagem , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Taxoides/uso terapêutico , Tegafur/administração & dosagem , Tegafur/efeitos adversos
10.
Jpn J Clin Oncol ; 49(11): 1009-1015, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31665358

RESUMO

OBJECTIVES: To explore the risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months in patients with unresectable locally advanced head and neck carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706 (UMIN000001272). METHODS: Forty-five patients received radiation therapy for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. Risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months were analyzed using Cox regression models and logistic regression models, respectively, with consideration to patient laboratory data just before chemoradiotherapy. Radiation fields were reviewed to analyze the relationship between the extent of the irradiated field and functional outcome. RESULTS: With a median follow-up period of 3.5 years, 3-year laryngo-esophageal dysfunction-free survival was 48.9%. For laryngo-esophageal dysfunction-free survival, hazards ratio of 2.35 in patients with nutritional support at registration (vs. without nutritional support; 95% confidence interval 0.96-5.76). For nutritional support dependence over 12 months, odds ratio was 6.77 in patients with hemoglobin less than the median of 13.4 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.24-36.85) and was 6.00 in patients with albumin less than the median of 3.9 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.11-32.54). Primary sites in disease-free patients with nutritional support dependence over 12 months were the oropharynx (N = 2) or hypopharynx (N = 1), and all pharyngeal constrictor muscles were included in irradiated fields with a curative dose. CONCLUSIONS: This supplementary analysis showed that pretreatment severe dysphagia requiring nutritional support, anemia and hypoalbuminemia might have a negative prognostic impact on long-term functional outcomes after curative chemoradiotherapy in head and neck cancer.


Assuntos
Quimiorradioterapia/efeitos adversos , Transtornos de Deglutição/terapia , Apoio Nutricional/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Anemia/dietoterapia , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Hipoalbuminemia/dietoterapia , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , Prognóstico , Tegafur/efeitos adversos , Tegafur/uso terapêutico
11.
Medicine (Baltimore) ; 98(31): e16673, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374045

RESUMO

The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The "liver reduction rate" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median "liver reduction rate" was 21%. The OS had statistically significant difference in nodal status (P = .032) and "liver reduction rate" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.


Assuntos
Colangiocarcinoma/radioterapia , Hepatopatias/prevenção & controle , Neoplasias Hepáticas/radioterapia , Lesões por Radiação/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Cisplatino/uso terapêutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/uso terapêutico , Piridinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dosagem Radioterapêutica , Radioterapia Adjuvante , Tegafur/uso terapêutico , Tomografia Computadorizada por Raios X
12.
Gan To Kagaku Ryoho ; 46(6): 1061-1063, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273176

RESUMO

A 76-year-old female patient was diagnosed with inoperable gastric cancer with distant lymph node metastasis(cT3N2M1 [LYM], cStage Ⅳ), for which she received S-1 chemotherapy(orally administered on days 1-14 ofa 28-day courses). The patient received a total of4 2 treatment courses. After an initial phase of stable disease due to chemotherapy, she eventually showed progressive disease. S-1 chemotherapy was discontinued. Because ofher social background, she decided against any further chemotherapy. After 1 year, she underwent metallic stent insertion through the gastric cancer, which enabled her to consume food. She is currently alive as of 5 years and 3 months from the date of first diagnosis.


Assuntos
Ácido Oxônico/uso terapêutico , Neoplasias Gástricas , Tegafur/uso terapêutico , Idoso , Combinação de Medicamentos , Feminino , Humanos , Linfonodos , Metástase Linfática , Neoplasias Gástricas/tratamento farmacológico
13.
Anticancer Res ; 39(7): 3931-3936, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262923

RESUMO

BACKGROUND/AIM: Platinum plus 5-fluorouracil (FP) is a first-line regimen of palliative chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma (RM-ESCC). In this retrospective study, we evaluated the efficacy and safety of S-1 monotherapy as a salvage line treatment for RM-ESCC, focusing on the reasons for discontinuation of prior FP. MATERIALS AND METHODS: The subjects of this study had RM-ESCC and received S-1 after failure of FP. RESULTS: Eleven patients were enrolled. Nine patients were refractory and two were intolerant to prior FP. The median progression-free survival and overall survival time were 3.0 and 11.7 months, respectively. Overall response rate was 22.2% and disease control rate of the 11 patients was 36.4%. Median relative dose intensity of 5-FU was 100% (range=85-100%). CONCLUSION: S-1 efficacy in RM-ESCC when given after FP was modest. Favorable OS may be attributed to good local control rather than to the efficacy of S-1 monotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Cisplatino/uso terapêutico , Combinação de Medicamentos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Terapia de Salvação , Falha de Tratamento
14.
Medicine (Baltimore) ; 98(30): e16667, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348323

RESUMO

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


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Intervalo Livre de Doença , Combinação de Medicamentos , Humanos , Metástase Neoplásica , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos
15.
BMC Cancer ; 19(1): 606, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221115

RESUMO

BACKGROUND: The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. METHODS: Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy. DISCUSSION: The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.


Assuntos
Adenocarcinoma/tratamento farmacológico , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , China , Intervalo Livre de Doença , Combinação de Medicamentos , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Oxaliplatina/uso terapêutico , Ácido Oxônico/uso terapêutico , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico , Adulto Jovem
16.
Int J Clin Oncol ; 24(10): 1190-1196, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31104175

RESUMO

BACKGROUND: How the interval between surgery and S-1 adjuvant chemotherapy (ACT), and S-1 relative dose intensity (RDI) affect prognosis in patients with stage II/III gastric cancer who undergo gastrectomy with D2 lymph node dissection followed by S-1 ACT is unclear. METHODS: We enrolled 95 patients with histopathologically confirmed gastric adenocarcinoma treated with gastrectomy with D2 dissection, followed by S-1 ACT. RESULTS: Per ROC analysis, we used 32 days as the optimal cut-off interval to divide patients into the delayed group (started ACT ≥ 32 days) and the non-delayed group ( < 32 days). Their 5-year overall survival (OS) rates differed significantly (delayed: 54.2%, non-delayed: 85.4%; P < 0.0001). Per ROC analysis of patients without recurrence within 1 year post-surgery, patients were divided into the high RDI (RDIHigh; ≥ 64.6%) and low RDI (RDILow; < 64.6%) groups. Their 5-year OS rates differed significantly (RDIHigh: 76.9%, RDILow: 63.7%; P = 0.012). In multivariate analysis, RDI and interval before starting ACT were independent prognostic indicators. Five- year OS rates by subgroups were RDIHigh/non-delayed: 84.0%, RDIHigh/delayed: 66.8%, RDILow/non-delayed: 100%, and RDILow/delayed: 48.2% (P < 0.0001). CONCLUSIONS: Early initiation and sufficient RDI for S-1 ACT can improve the prognosis of patients with stage II/III gastric cancer.


Assuntos
Adenocarcinoma/mortalidade , Antimetabólitos Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/mortalidade , Tegafur/uso terapêutico , Tempo para o Tratamento , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Taxa de Sobrevida
17.
Medicine (Baltimore) ; 98(20): e15696, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096513

RESUMO

Oxaliplatin plus S-1 (SOX) was a first-line regimen for advanced gastric cancer. The continuous administration of S-1 for 3 weeks can result in unacceptable gastrointestinal and hematological toxicities. Therefore, an alternative regimen (administration of S-1 for 1-week followed by 1-week rest) is warrant for improved tolerability and noninferiority efficacy. We conducted a study to evaluate the efficacy and safety of biweekly SOX as the first-line chemotherapy in patients with metastatic or advanced gastric cancer in China.Patients with metastatic or previously untreated advanced gastric cancer were enrolled. Oxaliplatin was administered intravenously at a dose of 85 mg/m on day 1, while S-1 was administered orally in doses of 80, 100, or 120 mg/day depending on different body surface areas of <1.25 m, 1.25-1.5 m, or >1.5 m respectively; the total dose of S-1 was administered twice daily on days 1-7 followed by a 7-day rest. This schedule was repeated every 2 weeks until disease progressed or intolerable toxicity occurred.Forty-six patients (M/F = 33/13) received biweekly oxaliplatin and S-1 as first-line chemotherapy. A total of 257 treatment cycles were administered and the median number of cycles administered was 6. Thirty-six patients (78.3%) received second-line chemotherapy. The median progression free survival and median overall survival was 4.4 months (95% CI, 3.37-5.36 months) and 10.3 months (95% CI, 8.88-11.3 months), respectively. The 1-year and 2-year survival rate was 41% and 13%. The objective response rate was 30.43%, and the disease control rate was 76.08%. The observed adverse events of Grade 3/4 included were leukocytopenia (13.04%); anemia (13.04%); neutropenia (15.22%); neurological toxicity (2.17%); diarrhea (2.17%).The biweekly SOX regimen as first-line treatment was active and well tolerated in Chinese patients with metastatic or advanced gastric cancer.


Assuntos
Oxaliplatina/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Intervalo Livre de Doença , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Estômago/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/secundário , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Resultado do Tratamento
18.
Jpn J Clin Oncol ; 49(8): 749-754, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31070750

RESUMO

BACKGROUND: S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). The addition of bevacizumab has been shown to significantly improve overall survival (OS) in patients with advanced non-squamous (NSq) NSCLC who received carboplatin plus paclitaxel, however, failed to show an OS advantage in patients who received cisplatin plus gemcitabine. METHODS: Chemotherapy-naive patients with Stage IIIB, IV or recurrent non-SQ NSCLC were treated with a 3-week cycle of S-1 80 mg/m2 on days 1-14, cisplatin 60 mg/m2 on day 8 and bevacizumab 15 mg/kg on day 8 for 4-6 cycles. Patients without progressive disease (PD) received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 80 mg/m2 every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile and Quality of life (QOL). RESULTS: From June 2013 to January 2015, 39 eligible patients were enrolled from eight institutions. Thirty-one patients (79%) completed four cycles of induction chemotherapy, and maintenance chemotherapy was initiated in 23 patients (59%). Median PFS, OS and ORR were 7.3 months (95% CI: 5.9-8.7), 21.4 months (95% CI: 14.7-not reached) and 64%, respectively. The most common grade 3/4 toxicities were leukopenia (12.8%), neutropenia (23.0%) and hypertension (28.2%). QOL analyses showed detrimental effects after initiation of the regimen. CONCLUSIONS: S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced NSq-NSCLC. RR was anticipated to be high with acceptable toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/efeitos adversos , Cooperação do Paciente , Qualidade de Vida , Análise de Sobrevida , Tegafur/efeitos adversos
19.
BMC Cancer ; 19(1): 416, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046709

RESUMO

BACKGROUND: Postoperative chemotherapy is beneficial for many pancreatic cancer patients. However, some patients require dose reduction or the discontinuation of adjuvant chemotherapy because of adverse treatment-related effects. In this study, we aimed to evaluate two main outcomes. First, we evaluated the clinicopathological factors affecting patient disease-free survival (DFS) and overall survival (OS) following upfront surgery. Second, we evaluated the factors that influence the continuity of adjuvant chemotherapy. METHODS: Fifty-four patients with resected pancreatic cancer were enrolled. First, we evaluated the clinicopathological factors affecting postoperative survival using the Kaplan-Meier method and Cox regression method. Next, factors affecting the continuity of adjuvant chemotherapy were analyzed using multiple logistic regression analysis. RESULTS: Univariate and multivariate analyses revealed that positive LN metastasis (HR (95% CI) 6.329 (2.381-16.95); p < 0.001) and relative dose intensity (RDI) < 80% for adjuvant chemotherapy (HR (95% CI) 5.154 (1.761-15.15); p = 0.003) were independent predictive factors for DFS. Regarding OS, extended dissection of the nerve plexus around the superior mesenteric artery (SMA) (HR (95% CI) 4.504 (1.721-11.76); p = 0.002), positive microscopic surgical margin (HR (95% CI) 5.565 (1.724-17.96); p = 0.004), and adjuvant chemotherapy of RDI < 80% (HR (95% CI) 3.534 (1.135-2.667); p = 0.029) were also independent predictive factors. Moreover, the level of RDI significantly correlated with DFS and OS. Multiple logistic regression analysis revealed that low RDI was significantly associated with postoperative body weight loss (BWL) ≥ 10%. CONCLUSIONS: The following factors were significantly associated with poor survival: extended dissection of the nerve plexus around the SMA, lymph node metastasis, residual tumor, and RDI of the adjuvant chemotherapy. Patient's prognosis with adjuvant chemotherapy of RDI < 80% was worse. BWL ≥10% was the most important factor affecting the continuity of adjuvant chemotherapy. Perioperative nutritional intervention is necessary for patients who receive adjuvant chemotherapy for advanced pancreatic cancer.


Assuntos
Desoxicitidina/análogos & derivados , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Tegafur/uso terapêutico , Perda de Peso , Idoso , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
20.
Trials ; 20(1): 242, 2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31029154

RESUMO

BACKGROUND: Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms' tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. METHODS: This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. DISCUSSION: Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179 . Registered on 9 April 2017.


Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Células Dendríticas/transplante , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/terapia , Fragmentos de Peptídeos/imunologia , Tegafur/uso terapêutico , Proteínas WT1/imunologia , Adulto , Idoso , Vacinas Anticâncer/efeitos adversos , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Células Dendríticas/imunologia , Método Duplo-Cego , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ácido Oxônico/efeitos adversos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tegafur/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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