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1.
Anticancer Res ; 41(4): 2141-2145, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813425

RESUMO

BACKGROUND/AIM: We compared the outcome of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for unresectable locally advanced thoracic esophageal cancer (EC) with that of cisplatin (CDDP) and 5-fluorouracil (5-FU) as combination chemoradiotherapy (CF-RT) in clinical settings. PATIENTS AND METHODS: Seventy-three patients with unresectable locally advanced thoracic EC were included in this study. CF (n=38) consisted of intravenous CDDP at 70 mg/m2 (day 1) and 5-FU at 700 mg/m2 (days 1 to 4), repeated every four weeks for two cycles. DCF (n=35) consisted of intravenous docetaxel at 50 mg/m2 (day 1), CDDP at 60 mg/m2 (day 1), and 5-FU at 600 mg/m2 (days 1 to 4), repeated every four weeks for two cycles. Patients were irradiated with 60 Gy in 30 fractions. RESULTS: The overall complete response (CR) rate of DCF-RT was significantly higher than that of CF-RT (36.7% vs. 3.7%, p=0.003). The 3-year overall survival (OS) rate of DCF-RT was significantly higher than that of CF-RT (32.8% vs. 8.5%, p<0.001). CONCLUSION: DCF-RT demonstrated a higher CR rate and OS for unresectable locally advanced thoracic EC than CF-RT.


Assuntos
Quimiorradioterapia , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Esofágicas/terapia , Fluoruracila/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Progressão da Doença , Docetaxel/efeitos adversos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Japão/epidemiologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(1): 32-38, 2021 Jan 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33678634

RESUMO

OBJECTIVES: Neoadjuvant chemotherapy combined with radical surgery has become the treatment model for locally advanced rectal cancer. The purpose of this study was to evaluate the safety and efficacy of postoperative mFOLFOX6 regimen chemotherapy for locally resectable advanced rectal cancer. METHODS: This was a prospective study. A total of 82 patients with locally advanced rectal cancer admitted to Affiliated Nanhua Hospital, University of South China from February 2015 to December 2017 were selected as the subjects. The patients received 4 courses of mFOLFOX6 chemotherapy and underwent surgery within 4-6 weeks after chemotherapy. The incidences of chemotherapy-related adverse reactions, postoperative complications, and clinical pathological reactions were analyzed. RESULTS: In the period from mFOLFOX6 chemotherapy to preoperative, 82 patients with locally advanced rectal cancer was reported chemotherapy-related adverse reactions, including Grade 4 neutropenia (2.4%), catheter related infection (2.4%), and anorexia (2.4%), Grade 3 nausea (2.4%) and anorexia (2.4%), Grade 2 neutropenia (14.6%) and peripheral neuropathy (7.3%). Finally, 76 patients with locally advanced rectal cancer completed surgery, including 56 (73.7%) with anterior rectum resection, 16 (21.1%) with abdominal perineal resection, and 72 (94.7%) with pelvic nerve preservation. A total of 22 (28.9%) patients had surgical complications, including 8 (10.5%) with complications of Grade 3 or above. The complications with high incidence were intestinal obstruction, anastomotic leakage, and sepsis. Among the 76 patients who completed chemotherapy and surgery, T stage was decreased in 28 (36.8%) and N stage was decreased in 44 (57.9%); forty-two (55.3%) were in pathological Stage I, 20 (26.3%) in Stage IIA, 12 (15.8%) in Stage IIB, and 2 (2.6%) in Stage IIIA. Ten patients were suspected of tumor invasion of surrounding organs before chemotherapy, of which 4 patients did not need to extend the resection of surrounding organs after chemotherapy and achieved R0 resection of tumor; 2 in T4b stage before chemotherapy received extended resection of surrounding organs, and the postoperative pathological result was T3, and achieved R0 resection; 1 diagnosed as poorly differentiated adenocarcinoma with seminal vesicle invasion in the evaluation before chemotherapy had T-stage progression after operation. There were 66 (86.8%) patients of partial response (PR), 9 (11.8%) of stable disease (SD) and 1 (1.3%) of progressive disease (PD). There was no complete response (CR) and no new lesion. CONCLUSIONS: Preoperative mFOLFOX6 regimen chemotherapy for locally resectable advanced rectal cancer is a safe and feasible treatment strategy, and it is worthy of clinical application.


Assuntos
Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , China , Fluoruracila/efeitos adversos , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Resultado do Tratamento
3.
Curr Cardiol Rep ; 23(3): 17, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33537861

RESUMO

PURPOSE OF REVIEW: 5-fluorouracil (5-FU) is one of the most common causes of cardiotoxicity associated with chemotherapy. The manifestations of 5-FU cardiotoxicity are diverse, and there are no established clinical guidelines addressing the diagnosis and management of this condition. Here we summarize the mechanistic and clinical data available to guide clinicians in caring for patients with suspected 5-FU cardiotoxicity. RECENT FINDINGS: The decision to resume 5-FU treatment in patients with suspected cardiovascular toxicity remains challenging. Testing for predisposing genetic variants may be helpful, particularly in patients with other signs of 5-FU toxicity. Uridine triacetate is a recently approved antidote that can improve clinical outcomes in patients with life-threatening fluoropyrimidine cardiotoxicity. 5-FU cardiotoxicity remains poorly understood, with limited mechanistic or prospective clinical trial data available to define risk factors or effective management strategies. Risk stratification and therapeutic decisions should be individualized, based on the risk-benefit ratio of continuing 5-FU therapy for each patient.


Assuntos
Miocardite , Cardiotoxicidade/etiologia , Morte Súbita , Fluoruracila/efeitos adversos , Humanos , Estudos Prospectivos
4.
Bull Cancer ; 108(1): 80-89, 2021 Jan.
Artigo em Francês | MEDLINE | ID: mdl-33423780

RESUMO

Despite its status as a rare disease, the incidence of the squamous cell carcinoma of the anus (SCCA) is surging, especially in its metastatic form. In addition, the prognosis of initially localized diseases has not substantially changed since the 1970s with a recurrence rate of between 25-40 % after the chemoradiotherapy. The updated data from 115 patients included in the Epitopes-HPV01 and Epitopes-HPV02 trials, confirm the modified regimen of DCF (mDCF) as the treatment of choice for patients with advanced SCCA given the rate of sustained remissions and complete molecular responses observed. The carboplatin-paclitaxel regimen may be considered as an option for patients with contraindication to cisplatin or 5-FU. In chemo-refractory patients, the efficacy of anti-PD-1/PD-L1 in monotherapy is limited and only brings benefit to 10-20 % of patients, and its use cannot be generalized in the absence of an association potentiating its effectiveness. In order to better understand the immunological parameters associated with advanced SCCA, an analysis of peripheral immune responses was carried out in the Epitopes-HPV01 and 02 trials. It demonstrated the key role of CD4 Th1 specific responses of telomerase and M-MDSC as main prognostic factors for the therapeutic efficacy of DCF. Numerous combination trials are currently underway or will soon begin in localized SCCA, as well as in the first and second-line in the advanced stage. Finally, the detection of circulating tumor DNA of HPV oncoprotein E6 and E7 (HPVtc), especially by the "digital droplet PCR" technique, is highly sensitive and specific, and can be used in daily practice.


Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Alphapapillomavirus/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/imunologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Contraindicações de Medicamentos , DNA Viral/análise , Fluoruracila/efeitos adversos , Humanos , Imunidade Celular , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Telomerase/imunologia
5.
Anticancer Res ; 41(1): 533-541, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419853

RESUMO

BACKGROUND/AIM: We compared the efficacy and safety of second-line FOLFIRI with bevacizumab (Bmab) or aflibercept (AFL) in patients with unresectable metastatic colorectal cancer (mCRC) to clarify selection criteria for anti-angiogenic agents. PATIENTS AND METHODS: The subjects were patients with mCRC who received second-line FOLFIRI in combination with Bmab or AFL. The primary endpoint was median overall survival (OS). Secondary endpoints were median time to treatment failure (TTF), overall response rate (ORR) and incidence of adverse events. RESULTS: Data from 26 patients in the Bmab group and 19 in the AFL group were analyzed. Median OS was slightly longer in the AFL group compared to the Bmab group, whereas median TTF was similar. ORR tended to be higher in the AFL group. The incidence of ≥grade 2 diarrhea and proteinuria was significantly higher in the AFL group than the Bmab group. CONCLUSION: In patients given combination treatment with FOLFIRI for second-line treatment of mCRC, AFL can increase response rates compared to Bmab, which may contribute to longer survival.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/mortalidade , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Retratamento , Resultado do Tratamento
6.
Int J Clin Oncol ; 26(4): 701-707, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33386556

RESUMO

BACKGROUND: The triplet-agent (5-fluorouracil/leucovorin, oxaliplatin, and irinotecan; FOLFOXIRI) combined with an anti-epidermal growth factor receptor antibody as a first-line treatment of metastatic colorectal cancer (mCRC) has shown promising results in Western trials. This phase Ib study assessed the safety of FOLFOXIRI plus cetuximab in Japanese patients with RAS wild-type mCRC. METHODS: Patients with previously untreated RAS wild-type mCRC received weekly cetuximab (400 mg/m2 at week 1 and subsequently 250 mg/m2) plus FOLFOXIRI that consisted of irinotecan (100, 120, and 150 mg/m2 defined as dose levels 0, 1, and 2), followed by oxaliplatin 85 mg/m2 and l-leucovorin 200 mg/m2 and then 5-fluorouracil 2400 mg/m2. The dose level of irinotecan was escalated starting at dose level 1 in a 3 + 3 manner. The primary endpoint was to determine the maximum-tolerated dose (MTD) and the recommended phase-2 dose (RP2D). Secondary endpoints included safety, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: Nine patients were enrolled. The MTD was not reached at dose level 2 and the RP2D was 150 mg/m2 irinotecan. The most frequent grade 3/4 adverse events were neutropenia (44%), fatigue (11%), paronychia (22%), and acneiform rash (11%). No dose-limiting toxicities occurred in any of the enrolled patients. No treatment-related death was observed. The ORR was 89% (95% confidence interval 52-100%). CONCLUSION: The safety profile of the combination of cetuximab and FOLFOXIRI was acceptable and promising anti-tumor activity was demonstrated, supporting further study in patients with RAS wild-type mCRC.


Assuntos
Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Cetuximab/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Compostos Organoplatínicos
7.
Arch Oral Biol ; 123: 104998, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33485111

RESUMO

OBJECTIVES: This systematic review evaluated the effect of phytotherapeutics in the treatment and prevention of 5-fluorouracil (5-FU)-induced oral mucositis (OM) in animal models. DESIGN: A search was performed in PubMed/Medline, CENTRAL (The Cochrane Library), EMBASE, and Web of Science, including studies published up to January 2020. Only articles investigating the chemoinduction of OM by 5-FU in animal models were included. Eligibility was evaluated and data were extracted from the eligible studies following the predefined PICO questions. The Cochrane Collaboration Risk of Bias Assessment tool was used to evaluate the quality of the included studies. RESULT: A total of 503 articles were retrieved and 13 were included. The hamster was the animal model used in all included studies. The treatment method ranged from the topical application of ointment (n = 3), gel (n = 5) and extract (n = 3) to the oral ingestion of the phytotherapeutics (n = 3). Chamomilla recutita L. (n = 3) and Pistacia atlantica (n = 3) were the most used therapeutic agents. Although all studies were classified as high risk of bias, all of them reported promising results regarding the use of phytotherapeutics in the management of OM, including lower clinical and histopathological scores as well as healing, anti-inflammatory, antimicrobial, and antioxidant activities. CONCLUSION: Despite the high risk of bias of the studies, phytotherapy is a promising alternative for the treatment of 5-FU-induced OM, showing interesting results in terms of tissue healing and anti-inflammatory, antimicrobial and antioxidant activity.


Assuntos
Fitoterapia , Preparações de Plantas/uso terapêutico , Estomatite/tratamento farmacológico , Animais , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cricetinae , Fluoruracila/efeitos adversos , Matricaria/química , Pistacia/química , Estomatite/induzido quimicamente , Estomatite/prevenção & controle
8.
Rev Lat Am Enfermagem ; 28: e3363, 2020.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-33084773

RESUMO

OBJECTIVE: to evaluate the effect of oral cryotherapy compared to physiological serum on the development of oral mucositis in outpatient cancer patients using the 5-fluorouracil antineoplastic agent. METHOD: this is a controlled, randomized, double-blind, and multi-center clinical trial, conducted with 60 patients undergoing chemotherapy. The experimental group (n=30) used oral cryotherapy during the infusion of the 5-FU antineoplastic agent, while the control group (n=30) performed mouthwash with physiological serum at their homes. The oral cavity of the participants was assessed at three times: before randomization, and on the 7th and 14th days after using 5-FU. For data analysis, descriptive analyses and the ANOVA, paired t, and McNemar tests were used. RESULTS: there was no statistically significant difference between the experimental and control groups in the assessments regarding the grade of mucositis. However, cryotherapy presented the chance to reduce the presence of intragroup mucositis, between the first and second assessments (p=0.000126). CONCLUSION: cryotherapy did not obtain statistical significance in relation to oral hygiene with serum, but it proved to be effective intragroup. Record number: RBR-4k7zh3.


Assuntos
Antineoplásicos , Mucosite , Estomatite , Crioterapia , Fluoruracila/efeitos adversos , Humanos , Estomatite/induzido quimicamente , Estomatite/prevenção & controle
9.
Am J Clin Oncol ; 43(9): 654-659, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889836

RESUMO

OBJECTIVE: By using the Korean Pancreatic Cancer (K-PaC) registry, we compared the clinical outcomes of FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) in patients with metastatic pancreatic cancer (MPC). METHODS: We constructed a web-based database of 3748 anonymized patients diagnosed with pancreatic ductal adenocarcinoma. MPC patients who received first-line FFX or GNP were enrolled. Overall survival (OS), progression-free survival, grade III to IV toxicity, and cross-over treatment were analyzed. RESULTS: A total of 413 patients (232 vs. 181, FFX vs. GNP; all data are presented in this sequence) were eligible. Median age was 63 years (60 vs. 69 y) with 43% (39% vs. 47%) comprising female individuals. The major metastatic sites were the liver (64%), peritoneum (25%), and distant lymph nodes (18%). The median OS was 11.5 versus 12.7 months (hazard ratio [HR]=0.87, 95% confidence interval [CI]: 0.68-1.12, P=0.286), and median progression-free survival was 7.5 versus 8.1 months (HR=0.92, 95% CI: 0.70-1.20, P=0.517), respectively. The frequency of grade III to IV febrile neutropenia was higher in the FFX group (18% vs. 11%, P=0.040), and that of peripheral neuropathy was higher in the GNP group (8% vs. 14%, P=0.046). The chance to receive second-line chemotherapy was higher in the GNP group (45% vs. 56%, P=0.036). In the cross-over treatment, the median OS of the FFX-GNP group (n=43) and the GNP-FFX group (n=47) was 16.8 versus 17.7 months (HR=0.79, 95% CI: 0.44-1.41, P=0.425). CONCLUSIONS: FFX and GNP showed similar efficacy and comparable toxicity in MPC patients. Although the GNP group had a higher chance to receive second-line chemotherapy, they did not have improved overall survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Peritoneais/secundário , Idoso , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/secundário , Estudos Cross-Over , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Neutropenia Febril/induzido quimicamente , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Irinotecano/efeitos adversos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Intervalo Livre de Progressão , Sistema de Registros , República da Coreia , Taxa de Sobrevida , Resultado do Tratamento
10.
Medicine (Baltimore) ; 99(33): e21743, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872062

RESUMO

INTRODUCTION: FOLFOX therapy is the main chemotherapy regimen for colorectal cancer. Peripheral neuropathy, hematotoxicity, and digestive symptoms are known to be the most frequent adverse events. Hyperammonemia and lactic acidosis rarely occur simultaneously during treatment with FOLFOX therapy; the number of case reports is limited worldwide. We report a case of disturbance of consciousness, considered to be caused by hyperammonemia and lactic acidosis that occurred during treatment with mFOLFOX6 therapy that was administered as postoperative adjuvant treatment for rectal cancer. PATIENT CONCERNS: This case was of a 71-year-old man who had been receiving oral treatment for chronic kidney disease and diabetes mellitus. Laparoscopic low anterior resection and artificial anal construction surgery were performed for stage III rectal cancer. As adjuvant postoperative therapy, mFOLFOX6 therapy was started but was followed by a disturbance of consciousness. DIAGNOSES: Results of the blood tests revealed notable hyperammonemia (ammonia level, 1,163 µg/dl) and lactic acidosis (pH 7.207; lactate, 17.56 mmol/L); however, imaging diagnosis did not reveal intracranial lesions that could cause disturbance of consciousness. INTERVENTIONS: For hyperammonemia, branched-chain amino acid agents and Ringers solution supplementation were administered. For acidosis, 7% sodium hydrogen carbonate was administered as treatment. OUTCOMES: The disturbance of consciousness improved within 12 hours of initiating the treatment, and the patient was discharged with no sequelae on 7th day after hospitalization. CONCLUSION: In patients with chronic kidney disease, FOLFOX regimen may confer risks of hyperammonemia and lactic acidosis.


Assuntos
Acidose Láctica/complicações , Antimetabólitos Antineoplásicos/efeitos adversos , Transtornos da Consciência/etiologia , Fluoruracila/efeitos adversos , Hiperamonemia/complicações , Acidose Láctica/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Hiperamonemia/induzido quimicamente , Masculino , Neoplasias Retais/tratamento farmacológico
11.
J Vasc Interv Radiol ; 31(10): 1600-1608, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32861569

RESUMO

PURPOSE: To compare survival after CT-guided percutaneous irreversible electroporation (IRE) and folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy versus FOLFIRINOX only in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: A post hoc comparison was performed of data derived from a prospective IRE-FOLFIRINOX cohort and a retrospective FOLFIRINOX-only cohort. All patients received a minimum of 3 cycles of FOLFIRINOX for LAPC and were considered eligible for CT-guided percutaneous IRE. Endpoints included overall survival (OS), local and distant progression-free survival, and time to progression (TTP) and were compared using stratified Kaplan-Meier analysis. Patients who received > 8 cycles of FOLFIRINOX before IRE and who had tumors > 6 cm in the FOLFIRINOX-only group were excluded. RESULTS: Of 103 patients with a diagnosis of LAPC, 52 were deemed eligible (n = 30 IRE-FOLFIRINOX and n = 22 FOLFIRINOX-only). Patients in the FOLFIRINOX-only arm had larger tumors (53 mm ± 19 vs 38 mm ± 7, P = .340), had more locoregional lymph node metastases (23% vs 7%, P = .622), and more often received radiotherapy (7 patients vs 2 patients, P = .027); all other baseline characteristics were comparable. Median OS was 17.0 months (range, 5-35 mo; SD = 6) for IRE-FOLFIRINOX versus 12.4 months (range, 3-22 mo; SD = 6) for FOLFIRINOX-only (P = .038). After sensitivity analyses, median OS was 17.2 months (range, 6-27 mo; SD = 6) versus 12.4 months (range, 7-32 mo; SD = 10) (P = .05). Median TTP was longer in the IRE-FOLFIRINOX group: 14.2 months (range, 5-25 mo; SD = 4) versus 5.2 months (range, 2-22; SD = 6) (P = .0001). CONCLUSIONS: In patients with LAPC after FOLFIRINOX chemotherapy, CT-guided percutaneous IRE may improve OS and TTP. This study may facilitate the design of randomized controlled trials to compare survival after IRE-FOLRINOX versus FOLFIRINOX-only.


Assuntos
Técnicas de Ablação , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Eletroporação , Neoplasias Pancreáticas/terapia , Radiografia Intervencionista , Tomografia Computadorizada por Raios X , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Radiografia Intervencionista/efeitos adversos , Radiografia Intervencionista/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/mortalidade , Resultado do Tratamento
12.
Anticancer Res ; 40(8): 4655-4661, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727789

RESUMO

In recent years, therapeutic drug monitoring (TDM) of intravenous administration of 5-fluorouracil (5-FU) has resulted in reduced toxicity and improved efficacy. Prodrugs of 5-FU were developed to reduce toxicity, extend the duration of action, and increase tumour selectivity of 5-FU. These drugs are important in daily practice because of their ease of administration. Dose adjustment of 5-FU prodrugs by TDM is expected to reduce its toxicity and improve its efficacy. This review focuses on data from a recent study of personalized treatment using TDM of 5-FU and its prodrugs.


Assuntos
Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Pró-Fármacos/administração & dosagem , Pró-Fármacos/efeitos adversos , Monitoramento de Medicamentos/métodos , Humanos , Neoplasias/tratamento farmacológico
13.
Acta Cir Bras ; 35(5): e202000504, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32638844

RESUMO

PURPOSE: 5-flourourasil (5-FU) is commonly used for early intraperitoneal chemotherapy in colorectal or appendiceal cancer patients with peritoneal carcinomatosis. Due to its effect, anastomosis healing can be impaired and leads to anastomotic leakage. In this study, we aimed to investigate the potential healing effect of platelet-rich plasma (PRP) on colonic anastomosis impaired by intraperitoneal 5-flourouracil application. METHODS: After ten rats were sacrificed for preparing PRP, forty Wistar-albino rats were subjected to colonic anastomosis, and randomly allocated into four groups including 10 rats each. According to receiving PRP and/or 5-FU application, the groups were formed as control (C), 5-FU without PRP (CT), anastomosis with PRP (C-PRP), and 5-FU with PRP (CT-PRP). CT and CT-PRP groups also received 5-FU intraperitoneally on postoperative day 1 (POD 1). All animals were euthanized on pod 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxiprolin (TH) and histopathological examination of each group were analyzed. RESULTS: 5-FU application significantly reduced ABP levels when compared with group C, C-PRP and CT-PRP (for each comparison, p<0,01). PRP application in CT-PRP group raised the measure of ABP up to the levels of C group. Although tissue hydroxyproline levels (THL) levels of CT-PRP group were found higher than CT group, it was not significant (p=0.112). Microscopically, comparing with CT group, PRP application significantly promoted the healing of colonic anastomosis subjected to 5-FU application by improving tissue edema, necrosis, submucosal bridging and collagen formation (p<0.05). Tissue healing in CT-PRP group was observed as good as the control groups. (C, C-PRP, p=0.181, p=0.134; respectively). CONCLUSION: PRP administration on colonic anastomosis significantly promotes the healing process of anastomosis in rats receiving 5-FU. This result encourages further clinical use of PRP to reduce the frequency of AL in patients receiving EPIC.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Colo , Fluoruracila , Plasma Rico em Plaquetas , Cicatrização , Anastomose Cirúrgica , Animais , Fluoruracila/efeitos adversos , Hidroxiprolina , Ratos , Ratos Wistar
14.
Tumour Biol ; 42(6): 1010428320925237, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32484056

RESUMO

The KCNB1 gene variants were differentially associated with cancers. However, their association with colorectal cancer has not yet been explored. We investigated the contribution of the KCNB1 gene variants rs3331, rs1051295, and indel (insertion/deletion) rs11468831 Polymorphism as predictors of the treatment response in colorectal cancer patients. A retrospective study, which involved 291 Tunisian colorectal cancer patients (aged 60.0 ± 13.1 years), who were stratified into responder and non-responder groups, according to TNM stages and their responsiveness to chemotherapy based on fluorouracil. KCNB1 genotyping was performed with amplification-refractory mutation system-polymerase chain reaction, and was confirmed by Sanger sequencing. Sex-specific response was found and colorectal cancer females are less likely to achieve a positive response during the chemotherapy strategy, compared to males. Weight and body mass index, tumor size, and tumor localization are considered as predictive factors to treatment responsiveness. Carriage of rs11468831 Ins allele was significantly associated with successful therapy achievement (p adjusted < 0.001). Stratification of colorectal cancer patients' response according to tumor localization and TNM stages reveals negative association of rs3331 Major allele to treatment response among the patients with advanced cancer stages (subgroup G2). The presence of rs3331 (homozygous minor) C/C genotype was positively associated with decline in carcino-embryonic antigen (p = 0.043) and CA19-9 (p = 0.014) serum levels. On the other hand, the presence of rs1051295 (homozygous minor) A/A genotype was correlated with marked decline in CA19-9 serum levels. KCNB1 haplotype did not reveal any association between haplotypes and treatment response. The results obtained suggest that gender-specific strategies for screening treatment and prevention protocols as well as KCNB1 variants may constitute an effective model for ongoing personalization medicine.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Estudos de Associação Genética , Canais de Potássio Shab/genética , Antígenos Glicosídicos Associados a Tumores/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Genótipo , Humanos , Mutação INDEL/genética , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Medicina de Precisão , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Caracteres Sexuais , Resultado do Tratamento
15.
Int J Clin Oncol ; 25(10): 1814-1821, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32594273

RESUMO

BACKGROUND: Oxaliplatin, one of the key cytotoxic drugs for colorectal cancer, frequently causes peripheral neuropathy which leads to dose modification and decreased patients' quality of life. However, prophylactic or therapeutic measures have not yet been established. Orally administered amino acids, cystine and theanine, promoted the synthesis of glutathione which was one of the potential candidates for preventing the neuropathy. The aim of this study was to determine whether daily oral administration of cystine and theanine attenuated oxaliplatin-induced peripheral neuropathy (OXLIPN). METHODS: Twenty-eight colorectal cancer patients who received infusional 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) therapy were randomly and evenly assigned to the cystine and theanine group and the control group. OXLIPN was assessed up to the sixth course using original 7-item questionnaire as well as Common Terminology Criteria for Adverse Events (CTCAE) grading scale. RESULTS: Neuropathy scores according to our original questionnaire were significantly smaller in the cystine and theanine group at the fourth (p = 0.026), fifth (p = 0.029), and sixth course (p = 0.038). Furthermore, significant differences were also observed in CTCAE neuropathy grades at the fourth (p = 0.037) and the sixth course (p = 0.017). There was one patient in each group who required dose reduction due to OXLIPN. Except for neurotoxicity, no significant differences were noted in the incidence of adverse events, and the total amount of administered oxaliplatin. CONCLUSION: The results demonstrated the daily oral administration of cystine and theanine attenuated OXLIPN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Glutamatos/administração & dosagem , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Administração Oral , Idoso , Cistina/administração & dosagem , Feminino , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/administração & dosagem , Projetos Piloto , Qualidade de Vida
16.
Anticancer Res ; 40(5): 2701-2706, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366415

RESUMO

BACKGROUND/AIM: Oral mucositis, which occurs frequently in the treatment of cancer, is a major problem. In this study, we aimed to develop a rat model of oral mucositis induced by cancer chemotherapy for quantitative measurement. MATERIALS AND METHODS: A model animal of oral mucositis was prepared by injecting an acetic acid aqueous solution into the buccal mucosa of rats to which a 5-FU solution had been previously administered. The doses of 5-FU and acetic acid were examined, and a treatment experiment using Kenalog® was performed. RESULTS: The optimal dose of the 5-FU solution and the optimal concentration of the acetic acid aqueous solution were 40 mg/kg and 25%, respectively. Treatment with Kenalog® confirmed that this model mimics immunocompromised oral mucositis. CONCLUSION: Compared with a mouse model, oral mucositis can be easily observed in this model and provides a large amount of oral mucosal tissue.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Estomatite/induzido quimicamente , Animais , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Contagem de Leucócitos , Masculino , Ratos Wistar , Estomatite/sangue , Úlcera/induzido quimicamente
17.
J Food Sci ; 85(6): 1872-1890, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32460371

RESUMO

Cancer represents a major disease burden worldwide. Despite continuous advances obtained in medical therapies recently, resistance to standard drugs and adverse effects still represent important causes of therapeutic failure. There is growing evidence that the gut microbiota can affect the response to chemo- and immunotherapeutic drugs by modulating efficacy and/or toxicity, and diet is the most important factor affecting the gut microbiota. In this study, we assessed the auxiliary antitumor effects of immunomodulatory fungal proteins from Hericium erinaceus (HEP) administered with the chemotherapy drug 5-Fluorouracil (5-Fu), and we attempted to identify new potential prebiotic bacteria for auxiliary antitumor treatment. There were 1,455 proteins identified from H. erinaceus. In a xenografted mouse model of cancer, HEP with 5-Fu significantly suppressed tumor growth, inhibited inflammatory markers such as interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS), and regulated the expression of Akt, CCDN1, CKD4, FOXM1, MMP7, MYC, PPAR-α, and PPAR-γ. 16S rRNA sequencing showed that HEP ameliorated the dysbacteriosis induced by 5-Fu, as it inhibited certain aerobic and microaerobic bacteria including Parabacteroides, Flavobacteriaceae, Christensenellaceae, Anoxybacillus, Aggregatibacter, Comamonadaceae, Planococcaceae, Desulfovibrionaceae, Sporosarcina, Staphylococcus, Aerococcaceae, and Bilophila in the xenografted mice, and increase some probiotic bacteria such as Bifidobacterium, Gemellales, Blautia, Sutterella, Anaerostipes, Roseburia, Lachnobacterium, Lactobacillus, and Desulfovibrio. This demonstrates that HEP could promote the antitumor efficacy of 5-Fu by improving the microbiota composition, the immune inflammatory response, and homeostasis.


Assuntos
Basidiomycota/química , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Proteínas Fúngicas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Neoplasias/microbiologia , Prebióticos/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Disbiose/induzido quimicamente , Disbiose/imunologia , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Proteínas Fúngicas/química , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
18.
Int J Clin Oncol ; 25(8): 1515-1522, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32409917

RESUMO

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


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
Future Oncol ; 16(20): 1417-1424, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32466683

RESUMO

Gastric cancer patients with severe peritoneal metastases, defined as massive ascites and/or inadequate oral intake, have been excluded from clinical trials of new treatments due to poor prognosis and tumor-related complications, such as ileus. Based on the results of the JCOG1108/WJOG7312G study, their prognosis when treated with 5-fluorouracil/l-leucovorin or 5-fluorouracil/l-leucovorin plus paclitaxel remained extremely poor in this setting. Retrospective studies have shown the promising efficacy of the modified FOLFOX6 (mFOLFOX6) regimen, with improved ascites and oral intake. Therefore, we planned a Phase II study of mFOLFOX6 in gastric cancer patients with severe peritoneal metastases (jRCTs041180007). The primary end point is overall survival, with an exploratory analysis comparing the findings with those of the JCOG1108/WJOG7312G study using Bayes' theorem. Trial registration Identifier: jRCTs041180007 (jRCTs: the Japan Registry of Clinical Trials).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Ascite/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Esquema de Medicação , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Japão , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Estudos Multicêntricos como Assunto , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Prognóstico , Segurança
20.
Medicine (Baltimore) ; 99(17): e19480, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332600

RESUMO

BACKGROUND: The digestive tract malignancies are a series of malignant tumor with high morbidity and mortality. Traditional Chinese medicine (TCM) combined with chemotherapy drugs interventions have been applied for the treatment of malignant tumors in Asian countries for dacades. This study aimed to assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for treating digestive tract malignancies. PURPOSE: To assess the effectiveness and safety on the combination of Kanglaite injection and fluorouracil-based chemotherapy for digestive tract malignancies. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when conducting the meta-analysis. Randomized controlled trials (RCTs) of Kanglaite injection combined with fluorouracil-based chemotherapy in the treatment of digestive tract malignant tumors were selected and assessed for inclusion. RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) was used for meta-analysis. The objective response rate (ORR) was defined as the primary endpoint, and the disease control rate (DCR), quality of life (QoL), and toxicities were the secondary outcomes. RESULTS: 20 RCTs enrolling 1339 patients with advanced digestive tract malignancies were included. The methodological quality of most included trials was low to moderate. Compared with fluorouracil-based chemotherapy alone, Kanglaite injection plus fluorouracil-based chemotherapy can improve DCR (risk ratio (RR) = 1.18, 95% confidence interval (CI) 1.11-1.25, P < .00001), ORR (RR = 1.35, 95% CI 1.18-1.54, P < .00001), QoL (RR = 1.58, 95% CI 1.35-1.85, P < .00001), and can reduce adverse drug reactions (ADRs) such as myelosuppression (RR = 0.33, 95% CI 0.25-0.43, P < .00001), leukopenia (RR = 0.31, 95% CI 0.22-0.43, P < .00001), thrombocytopenia (RR = 0.6, 95% CI 0.38-0.49, P = .03), neutropenia (RR = 0.26, 95% CI 0.12-0.55, P = .0005), anemia (RR = 0.41, 95% CI 0.23-0.75, P = .004), gastrointestinal reaction (RR = 0.35, 95% CI 0.27-0.46, P < .00001), nausea/vomiting (RR = 0.41, 95% CI 0.28-0.61, P < .00001), diarrhea (RR = 0.34, 95% CI 0.18-0.62, P = .0004), hepatotoxicity (RR = 0.28, 95% CI 0.17-0.47, P < .00001), neurotoxicity (RR = 0.58, 95% CI 0.41-0.82, P = .002), mucositis (RR = 0.59, 95% CI 0.29-1.21, P = .15). CONCLUSION: Kanglaite injection combined with fluorouracil-based chemotherapy could remarkably improve the clinical effectiveness and reduce the adverse effects in patients with advanced malignant tumors of the digestive tract which may provide evidence to judge whether TCM is an effective and safe intervention for the digestive tract malignancies.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Digestório/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fluoruracila/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Estadiamento de Neoplasias , Razão de Chances
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