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1.
Medicine (Baltimore) ; 99(6): e19029, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028414

RESUMO

When the 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy regimen is used to treat colorectal cancer (CRC), chemotherapy-induced peripheral neuropathy (CIPN) caused by oxaliplatin can substantially affect quality of life (QOL) in the CRC patients. This study compared emotional distress and QOL during FOLFOX in CRC patients with and without CIPN symptoms.This cross-sectional, descriptive, and comparative study recruited 68 CRC patients receiving FOLFOX at a local teaching hospital and at a medical center in southern Taiwan. Self-reported structured questionnaires (oxaliplatin-associated neuropathy questionnaire, profile of mood states short form, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30, version 3.0) were used for 1-time data collection. The Chi-square test, Fisher exact test, and Mann-Whitney U test were used to analyze data, and a P-value < .05 was considered statistically significant.The CIPN group had 45 (66.2%) patients, and the non-CIPN group had 23 (33.8%) patients. The 5 most common symptoms were coldness-related burning sensation or discomfort in the upper limbs, numbness in the upper limbs, tingling in the upper limbs, impairment of vision, and discomfort in the throat. The CIPN group had more females (P = .013), a more advanced stage of CRC (P = .04) and a higher chemotherapy dosage (P = .006). The 2 groups did not significantly differ in anxiety (P = .065) or depression (P = .135). Compared to the non-CIPN group, the CIPN group had significantly lower functioning (P = .001) and global health status (P < .001) and significantly more symptoms (P < .001).The CIPN group had significantly lower QOL compared to the non-CIPN group. However, the CIPN group did not have lower emotional distress compared to the non-CIPN group. The results of this study demonstrate the need for in-service courses specifically designed to train health professionals in assessing and managing CIPN symptoms to improve QOL in CRC patients receiving FOLFOX.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Qualidade de Vida , Estresse Psicológico/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/psicologia , Estudos Transversais , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Doenças do Sistema Nervoso Periférico/psicologia , Estresse Psicológico/etiologia , Inquéritos e Questionários
2.
Cancer Sci ; 111(1): 253-265, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785020

RESUMO

FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) is one of the main chemotherapy regimens for colorectal cancer (CRC), but only half of CRC patients respond to this regimen. Using gene expression profiles of 96 metastatic CRC patients treated with FOLFOX, we first selected gene pairs whose within-sample relative expression orderings (REO) were significantly associated with the response to FOLFOX using the exact binomial test. Then, from these gene pairs, we applied an optimization procedure to obtain a subset that achieved the largest F-score in predicting pathological response of CRC to FOLFOX. The REO-based qualitative transcriptional signature, consisting of five gene pairs, was developed in the training dataset consisting of 96 samples with an F-score of 0.90. In an independent test dataset consisting of 25 samples with the response information, an F-score of 0.82 was obtained. In three other independent survival datasets, the predicted responders showed significantly better progression-free survival than the predicted non-responders. In addition, the signature showed a better predictive performance than two published FOLFOX signatures across different datasets and is more suitable for CRC patients treated with FOLFOX than 5-fluorouracil-based signatures. In conclusion, the REO-based qualitative transcriptional signature can accurately identify metastatic CRC patients who may benefit from the FOLFOX regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/genética , Estudos de Avaliação como Assunto , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem , Intervalo Livre de Progressão , Transcrição Genética/efeitos dos fármacos , Transcrição Genética/genética , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
3.
J Cancer Res Clin Oncol ; 146(2): 493-501, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31691872

RESUMO

PURPOSE: In metastatic colorectal cancer (MCRC), mucinous histology has been associated with poor response rate and prognosis. We investigated whether bevacizumab combined with different chemotherapy regimens may have an impact on clinical outcomes of MCRC patients with mucinous histology. METHODS: 685 MCRC patients were classified in mucinous adenocarcinoma (MC) and non-mucinous adenocarcinoma (NMC) and were treated with first-line bevacizumab plus fluoropyrimidine (FP)-based, oxaliplatin (OXA)-based, irinotecan (IRI)-based, or FOLFOXIRI. RESULTS: Ninety-four (13.7%) patients had MC. With a median follow-up of 50 months, MC patients had a median overall survival (OS) of 28.2 months compared with 27.7 months for the NMC group [hazard ratio (HR) = 0.92; 95% confidence interval (CI) 0.70-1.19, P = 0.530]. The overall response rates for MC and NMC were 41.5% (95% CI 31.5-51.4) and 62.4% (95% CI 58.4-66.3), respectively (Chi-square test, P <0.003). After correcting for significant prognostic factors by multivariate Cox regression analysis, age, resection of the primary tumour, and number of metastatic sites were found to be associated with poorer OS, but not mucinous histology. CONCLUSION: Compared with NMC, MCRC patients with mucinous histology treated with bevacizumab plus chemotherapy had comparable OS despite lower overall response rate.


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Prognóstico , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 98(50): e18423, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852167

RESUMO

RATIONALE: Vulvar metastasis of colorectal cancer (CRC) and acquired resistance to cetuximab is a very rare phenomenon. To our knowledge, few cases have been reported in the English literatures. PATIENT CONCERNS: A 55-year-old woman was diagnosed as adenocarcinoma of the rectum and the primary tumor was detected to be Kirsten-RAS (KRAS) wild type. DIAGNOSES: The patient was diagnosed with rectal adenocarcinoma by colonoscopy. Positron emission tomography/computed tomography (PET-CT) revealed multiple lymph node and bone metastases. INTERVENTIONS: The patient received a first-line course of palliative chemotherapy with FOLFOX combined with cetuximab. OUTCOMES: After an initial response, acquired resistance to cetuximab occurred and vulvar metastasis was established by a second biopsy. Further molecular analysis showed that the KRAS mutation was detected in plasma samples and tumor tissues. LESSONS: Vulvar metastasis from CRC is relatively rare and indicates a poor prognosis. Routine physical examinations of cutaneous and subcutaneous may facilitate early detection of metastases and timely intervention of medical technology. Moreover, combining serial tumor biopsy, liquid biopsy, and radiologic imaging could help to define mechanisms of drug resistance and to guide selection of therapeutic strategies.


Assuntos
Adenocarcinoma/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Retais/patologia , Neoplasias Vulvares/secundário , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/uso terapêutico , Evolução Fatal , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Pessoa de Meia-Idade , Mutação , Compostos Organoplatínicos/uso terapêutico , Neoplasias Vulvares/patologia
5.
Medicine (Baltimore) ; 98(52): e18513, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876741

RESUMO

BACKGROUND: This study evaluated the efficacy and safety of docetaxel combined with lobaplatin, relative to docetaxel combined with gemcitabine, for treating patients with recurrent metastatic breast cancer (rMBC). METHODS: Patients with rMBC received ≥2 cycles (21 days each) of either docetaxel and lobaplatin (DL; n = 21), or docetaxel and gemcitabine (DG; n = 22). On day 1 of each cycle, all patients were given 75 mg/m intravenous docetaxel. Patients in DL and DG were also given, respectively, 35 mg/m intravenous lobaplatin (day 2) or 1000 mg/m intravenous gemcitabine (days 1, 8). RESULTS: Five (11.6%) and 16 (37.2%) patients achieved complete remission and partial response, respectively; rates of response and disease control were 48.8%. The response rates of the groups were comparable (47.6%, 50.0%). The median survival times after relapse and metastasis of the DL group (18 months) were significantly less than that of the DG group (25 months). Median progression-free survivals after relapse and metastasis were similar (12 cf. 14 months). The main toxic side reaction was grade 2, with no treatment-related deaths. Rates of the following were comparable between DG and DL: grade 3 or 4 white blood cells (23.8%, 31.8%) and digestive tract toxicity (4.8%, 4.5%); neutropenia (28.6%, 22.7%); anemia (4.8%, nil); and thrombocytopenia (19.0%, 13.6%). Other toxicities included hepatic toxicity, myalgia, infection, and fatigue. CONCLUSIONS: Both the DL and DG regimens were associated with encouraging benefits, while treatment-related toxicity was manageable. Therefore, these regimens are effective options for treatment of rMBC. TRIAL REGISTRATION: This clinical trial study was approved by the Ethics Committee of Guizhou Cancer Hospital, and has been registered in the China Clinical Trial Center (December 8, 2014, No. ChiCTR-IPR-14005633).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclobutanos/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ciclobutanos/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Docetaxel/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Projetos Piloto , Análise de Sobrevida
6.
Medicine (Baltimore) ; 98(44): e17462, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689749

RESUMO

RATIONALE: Oxaliplatin is a key part of the standard treatment for colorectal cancer which is formally contraindicated in patients with severe renal dysfunction. Here, we investigated a safe and efficient dosing schedule of oxaliplatin in folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen by monitoring total and free platinum concentrations in plasma. PATIENT CONCERNS: A 47-year-old female with chronic hemodialysis was diagnosed with left-sided colon cancer and underwent colectomy. One year later, she was presented with omentum metastasis and needed further treatment. DIAGNOSES: The computed tomography (CT) scanning revealed multiple omental nodules. Positron emission tomography-CT (PET-CT) showed increased uptake of the nodules. INTERVENTIONS: The patient was treated with FOLFOX therapy every 3 weeks. The oxaliplatin began with 50 mg/m and gradually increased 85 mg/m as in the standard regimen. A 4-hour dialysis was started 1 hour after the end of oxaliplatin infusion. OUTCOMES: The free platinum concentration time curve showed a biomodel pattern. The Cmax of the 1st peak we observed in our patients at the standard dose is comparable to patients with normal renal function. This patient was treated with FOLFOX for 12 courses. No apparent adverse effect was observed during the treatment. LESSONS: The FOLFOX can be safely administered in hemodialysis patients on a long-term basis. Dose reduction of oxaliplatin is not necessarily needed if hemodialysis is performed soon after the infusion. Further studies are needed to distinguish between active and inactive oxaliplatin products during the 2nd peak of the free platinum concentration curve in this population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Glomerulonefrite/terapia , Oxaliplatina/uso terapêutico , Diálise Renal/métodos , Doença Crônica , Neoplasias do Colo/patologia , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/administração & dosagem
7.
BMC Cancer ; 19(1): 988, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647032

RESUMO

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Laparoscopia , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Custos e Análise de Custo , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Tempo de Internação , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
8.
Genes (Basel) ; 10(9)2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491988

RESUMO

High grade serous ovarian cancer (HGSOC) retains high molecular heterogeneity and genomic instability, which currently limit the treatment opportunities. HGSOC patients receiving complete cytoreduction (R0) at primary surgery and platinum-based therapy may unevenly experience early disease relapse, in spite of their clinically favorable prognosis. To identify distinctive traits of the genomic landscape guiding tumor progression, we focused on the R0 patients of The Cancer Genome Atlas (TCGA) ovarian serous cystadenocarcinoma (TCGA-OV) dataset and classified them according to their time to relapse (TTR) from surgery. We included in the study two groups of R0-TCGA patients experiencing substantially different outcome: Resistant (R; TTR ≤ 12 months; n = 11) and frankly Sensitive (fS; TTR ≥ 24 months; n = 16). We performed an integrated clinical, RNA-Sequencing, exome and somatic copy number alteration (sCNA) data analysis. No significant differences in mutational landscape were detected, although the lack of BRCA-related mutational signature characterized the R group. Focal sCNA analysis showed a higher frequency of amplification in R group and deletions in fS group respectively, involving cytobands not commonly detected by recurrent sCNA analysis. Functional analysis of focal sCNA with a concordantly altered gene expression identified in R group a gain in Notch, and interferon signaling and fatty acid metabolism. We are aware of the constraints related to the low number of OC cases analyzed. It is worth noting, however, that the sCNA identified in this exploratory analysis and characterizing Pt-resistance are novel, deserving validation in a wider cohort of patients achieving complete surgical debulking.


Assuntos
Biomarcadores Tumorais/genética , Cistadenocarcinoma Seroso/genética , Variações do Número de Cópias de DNA , Neoplasias Ovarianas/genética , Antineoplásicos/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Acúmulo de Mutações , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Receptores Notch/genética , Recidiva
9.
Anticancer Res ; 39(9): 5089-5096, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519620

RESUMO

BACKGROUND/AIM: We evaluated the clinical impact of FOLFOXIRI regimen aiming for conversion surgery in patients with unresectable multiple colorectal liver metastasis (CRLM). PATIENTS AND METHODS: A total of 42 patients with unresectable multiple CRLM who received chemotherapy with molecular agents were included in the analysis. The clinical results of FOLFOXIRI with other regimens were compared. RESULTS: The total conversion rate of 42 unresectable CRLM was 48.1%, and conversion cases had a better prognosis. Clinicopathological characteristics of conversion cases were more frequent in FOLFOXIRI induction, liver limited disease and maximum diameter × number (MDN) over 70. FOLFOXIRI achieved a higher conversion rate compared to other regimens (72.2% vs. 37.5%, p=0.0334), and significantly reduced the medication period until conversion surgery (median 5.8 courses) with a higher tumour necrotic rate. Consequently, the overall survival of conversion cases with FOLFOXIRI was better than that with other regimens (p=0.0055). CONCLUSION: FOLFOXIRI plus molecular agents might provide a higher probability of conversion surgery with a prognostic benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Neoplasias Colorretais/diagnóstico , Terapia Combinada , Conversão para Cirurgia Aberta , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Resultado do Tratamento , Carga Tumoral
10.
Surgery ; 166(6): 959-966, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31395397

RESUMO

BACKGROUND: The safety and feasibility of laparoscopic, two-stage hepatectomy for bilobar colorectal liver metastases is poorly evaluated. METHODS: We reviewed retrospectively 86 consecutive patients who underwent complete two-stage hepatectomy (left lobe clearance as the first stage and standard/extended right hepatectomy as the second stage) for bilobar colorectal liver metastases between 2007 and 2017 in 2 tertiary centers. Short- and long-term outcomes were compared between laparoscopic and open two-stage hepatectomy before and after propensity score matching. RESULTS: Laparoscopic two-stage hepatectomy was performed in 38 patients and open two-stage hepatectomy in 48. After propensity score matching, 25 laparoscopic and 25 open patients showed similar preoperative characteristics. For the first stage, a laparoscopic approach was associated with lesser hospital stays (4 vs 7.5 days; P < .001). For the second stage, a laparoscopic approach was associated with less blood loss (250 vs 500 mL; P = .040), less postoperative complications (32% vs 60%; P = .047), lesser hospital stays (9 vs 16 days; P = .013), and earlier administration of chemotherapy (1.6 vs 2 months; P = .039). Overall survival, recurrence-free survival, and liver-recurrence-free survival were comparable between the groups (3-year overall survival: 80% vs 54%; P = .154; 2-year recurrence-free survival: 20% vs 18%; P = .200; 2-year liver-recurrence-free survival: 39% vs 33%; P = .269). Although both groups had comparable recurrence patterns, repeat hepatectomies for recurrence were performed more frequently in the laparoscopic two-stage hepatectomy group (56% vs 0%; P = .006). CONCLUSION: Laparoscopic two-stage hepatectomy for bilobar colorectal liver metastases is safe and feasible with favorable surgical and oncologic outcomes compared to open two-stage hepatectomy.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Laparoscopia/efeitos adversos , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Fluoruracila/uso terapêutico , Hepatectomia/métodos , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/métodos , Tempo de Internação/estatística & dados numéricos , Leucovorina/uso terapêutico , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Compostos Organoplatínicos/uso terapêutico , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos
11.
Nihon Shokakibyo Gakkai Zasshi ; 116(8): 676-684, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406073

RESUMO

A 42-year-old woman was referred to our hospital for the treatment of pyloric stenosis. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) revealed the presence of type 4 advanced gastric cancer with bladder metastasis and peritoneal dissemination. Biopsy specimen examination revealed poorly differentiated adenocarcinoma with signet ring cell carcinoma. Thus, two cycles of chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin were administered. Subsequently, the gastric lesion and bladder metastasis reduced as detected using EGD and CT. Consequently, she achieved adequate oral intake. After changing the regimen to tegafur/gimeracil/oteracil and oxaliplatin, she was discharged. Currently, she continues to receive chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/diagnóstico , Neoplasias da Bexiga Urinária/secundário , Adulto , Feminino , Humanos , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Neoplasias Gástricas/terapia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
12.
Int J Mol Sci ; 20(14)2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295913

RESUMO

Breast cancer (BC) is the most frequent oncologic cause of death among women and the improvement of its treatments is compelling. Platinum salts (e.g., carboplatin, cisplatin, and oxaliplatin) are old drugs still used to treat BC, especially the triple-negative subgroup. However, only a subset of patients see a concrete benefit from these drugs, raising the question of how to select them properly. Therefore, predictive biomarkers for platinum salts in BC still represent an unmet clinical need. Here, we review clinical and preclinical works in order to summarize the current evidence about predictive or putative platinum salt biomarkers in BC. The association between BRCA1/2 gene mutations and platinum sensitivity has been largely described. However, beyond the mutations of these two genes, several other proteins belonging to the homologous recombination pathways have been linked to platinum response, defining the concept of BRCAness. Several works, here reviewed, have tried to capture BRCAness through different strategies, such as homologous recombination deficiency (HRD) score and genetic signatures. Moreover, p53 and its family members (p63 and p73) might also be used as predictors of platinum response. Finally, we describe the mounting preclinical evidence regarding base excision repair deficiency as a possible new platinum biomarker.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Animais , Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Reparo do DNA , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Recombinação Homóloga , Humanos , Mutação , Farmacogenética
13.
Cancer Control ; 26(1): 1073274819864111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317770

RESUMO

Colorectal cancer is the third most common cancer and the second leading cause of death from cancer worldwide. In Vietnam, the disease is the fifth leading cancer (8.9%), with 14 733 new cases in 2018. In recent years, the mFolfox6 regimen has been indicated commonly as the adjuvant chemotherapy after curative resection for patients with colorectal cancer. However, the efficacy of the regimen in Vietnamese patients has not been assessed and reported. In this retrospective study, we reviewed medical records of 83 patients with stage II or stage III colorectal cancer who received mFOLFOX6 regimen in order to investigate simultaneously survival and safety of this chemotherapy regimen. Three-year overall and disease-free survival were 84.3% and 79.5%, respectively. Our data revealed that postoperative Carcinoma Embryonic Antigen (CEA) level was a significant prognostic factor for survival, with hazard ratio of 3.83 and 3.67, respectively (P < .05), for overall survival and disease-free survival in the elevated CEA level group when compared to the normal CEA level group. The regimen also demonstrated to be well tolerated and can be used in routine practice as an adjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/terapia , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante/métodos , Colectomia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Protectomia , Prognóstico , Estudos Retrospectivos , Vietnã/epidemiologia , Adulto Jovem
14.
Rom J Ophthalmol ; 63(2): 174-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334397

RESUMO

A 53-year-old male developed acute diminution of vision in his right eye while on FOLFOX chemotherapy for stage C colon cancer. Examination revealed bilateral optic nerve head swelling with flame shaped hemorrhages over the right optic disc and anomalous left retinal vasculature. Computed tomography scan of the brain and orbit revealed no cerebral pathology, however bilateral optic disc drusen (ODD) was suspected. B scan ultrasonography confirmed the presence of bilateral ODD. Fluorescein angiography showed early hypofluorescence of the right optic disc with bilateral late disc staining and a diagnosis of right anterior ischemic optic neuropathy (AION) with bilateral ODD was made. A literature review was performed and possible mechanisms for the development of AION in this case were discussed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Drusas do Disco Óptico/complicações , Disco Óptico/patologia , Neuropatia Óptica Isquêmica/etiologia , Acuidade Visual , Campos Visuais , Neoplasias do Colo/complicações , Neoplasias do Colo/diagnóstico , Angiofluoresceinografia , Fluoruracila/uso terapêutico , Fundo de Olho , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Drusas do Disco Óptico/diagnóstico , Neuropatia Óptica Isquêmica/diagnóstico , Compostos Organoplatínicos/uso terapêutico , Vasos Retinianos/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia
15.
Korean J Gastroenterol ; 73(6): 355-359, 2019 Jun 25.
Artigo em Coreano | MEDLINE | ID: mdl-31234626

RESUMO

Intussusception is a common in pediatric age group. But it is rare in adults. And intussusception caused by tumor account for 1% of bowel obstructions in adult. Intussusception is an extremely rare cause of abdominal pain in pregnancy. In particular, cases of Intussusception due to colorectal cancer during pregnancy have never been reported in Korea. Our patient is a 34 years old woman who presented at 14 weeks of her second pregnancy. She presented with right lower abdominal discomfort and intermittent palpable mass which was usually spontaneously resolved. In the MRI study, pathologic asymmetric wall thickening was still noted and ileocolic intussusception was noted, and in colonoscopy, there was ulcerofungating mass around ileocecal valve which may be a leading point of intussusception. Biopsy was done. Pathologic finding was poorly differentiated adenocarcinoma. Under the patient agreement, we performed dilatation and curettage and laparoscopic right hemicolectomy and lymph node dissection. Now she is receiving a FOLFOX chemotherapy.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Colo/diagnóstico , Intussuscepção/diagnóstico , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/complicações , Neoplasias do Colo/tratamento farmacológico , Colonoscopia , Feminino , Fluoruracila/uso terapêutico , Humanos , Intussuscepção/complicações , Intussuscepção/cirurgia , Laparoscopia , Leucovorina/uso terapêutico , Linfonodos/cirurgia , Imagem por Ressonância Magnética , Compostos Organoplatínicos/uso terapêutico , Gravidez , Ultrassonografia
16.
BMC Cancer ; 19(1): 567, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185985

RESUMO

BACKGROUND: Non-V600E BRAF mutated colorectal cancer (CRC) is a rare disease entity with specific clinical features. These tumors are less likely to have microsatellite instability than CRC with a V600E BRAF mutation and often harbor a KRAS or NRAS mutation. Notably, median overall survival is longer than in wild-type BRAF CRC. Little is known about treatment possibilities in these patients. CASE PRESENTATION: We present the case of a 59 year old patient with a rare mutation in BRAF codon 594, who progressed rapidly on all classical therapies but experienced a clear and long lasting response on treatment with Regorafenib. CONCLUSION: Little is known about therapies that can be effective in the rare non-V600E BRAF mutated CRCs. We present a patient who had a definite response to treatment with Regorafenib. There are no predictive markers that define a subset of CRC patients who benefit most from Regorafenib. The specific features of this non-V600E BRAF mutated CRC may be relevant in the exploration of predictive biomarkers for the efficacy of Regorafenib.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Compostos de Fenilureia/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridinas/uso terapêutico , Adenocarcinoma de Pulmão/secundário , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/sangue , Cetuximab/uso terapêutico , Neoplasias do Colo/patologia , Neoplasias do Colo/radioterapia , Neoplasias do Colo/cirurgia , Éxons/genética , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Leucovorina/uso terapêutico , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
JAMA Netw Open ; 2(5): e194154, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31099875

RESUMO

Importance: The results from the recent International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration have led some clinicians to adopt shorter durations of adjuvant chemotherapy for patients with stage III colon cancer. The extent to which these findings are supported by other data is unknown. Objective: To conduct a systematic review and meta-analysis of randomized and observational studies investigating the association between the duration of adjuvant chemotherapy and survival among individuals diagnosed as having stage II and III colon cancer (PROSPERO protocol CRD42018108711]). Data Sources: Abstracts published in English between 2003 and 2018 within the MEDLINE, Embase, CENTRAL, and CINAHL databases were reviewed by 2 authors. Also searched were conference proceedings and the indexes of high-impact oncology journals. Study Selection: Studies were excluded if they did not present original data; focused on animal populations, on cancers in sites other than the colon, or on patients with stage 0, I, or IV disease; did not examine a 5-flourouracil-based monotherapy or combination therapy; or did not evaluate the association between treatment duration and survival. The search identified 2341 articles, from which 2 randomized trials and 20 observational studies were included in the meta-analysis. Data Extraction and Synthesis: This study followed the PRISMA and MOOSE reporting guidelines. The risk of bias was assessed by 2 authors using the Cochrane and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tools. The results were synthesized using a random-effects model. Main Outcomes and Measures: The primary and secondary outcomes were overall survival and disease-free survival, respectively. It was hypothesized a priori that 3 months of chemotherapy would be as effective as 6 months of chemotherapy. Results: Twenty-two studies were included in the meta-analysis, representing 43 671 patients. The inclusion of patients with stage II disease or with rectal cancer was identified as a source of heterogeneity. After restricting the analysis to patients with stage III colon cancer, there was no association between the duration of chemotherapy and overall survival among studies involving FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) regimens (hazard ratio [HR], 0.80; 95% CI, 0.58-1.09). Among studies focused exclusively on monotherapy, the standard 6-month regimen relative to a 3-month regimen was associated with improved survival (HR, 0.59; 95% CI, 0.52-0.68). Conclusions and Relevance: Shortened durations of chemotherapy may reduce survival among patients with stage III colon cancer prescribed monotherapy but not a combination regimen.


Assuntos
Quimioterapia Adjuvante/mortalidade , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Estadiamento de Neoplasias , Estudos Observacionais como Assunto , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
18.
Future Oncol ; 15(18): 2073-2082, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31094225

RESUMO

Bemarituzumab is an afucosylated monoclonal antibody against FGFR2b (a FGF receptor) with demonstrated monotherapy clinical activity in patients with late-line gastric cancer whose tumors overexpress FGFR2b (NCT02318329). We describe the rationale and design of the FIGHT trial (NCT03343301), a global, randomized, double-blind, placebo-controlled Phase III study evaluating the role of bemarituzumab in patients with previously untreated, FGFR2b-overexpressing advanced gastroesophageal cancer. Patients are randomized in a blinded fashion to the combination of mFOLFOX6 and bemarituzumab or mFOLFOX6 and placebo. Eligible patients are selected based on the presence of either FGFR2b protein overexpression determined by immunohistochemistry or FGFR2 gene amplification determined by circulating tumor DNA. The primary end point is overall survival, and secondary end points include progression-free survival, objective response rate and safety.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos Clínicos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Junção Esofagogástrica/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Biomarcadores Tumorais , Neoplasias Esofágicas/diagnóstico , Junção Esofagogástrica/patologia , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Amplificação de Genes , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Projetos de Pesquisa , Neoplasias Gástricas/diagnóstico
19.
BMC Cancer ; 19(1): 421, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060539

RESUMO

BACKGROUND: Although the prognostic biomarkers associated with colorectal cancer (CRC) survival are well known, there are limited data on the association between the molecular characteristics and survival after recurrence (SAR). The purpose of this study was to assess the association between pathway mutations and SAR. METHODS: Of the 516 patients with stage III or high risk stage II CRC patients treated with surgery and adjuvant chemotherapy, 87 who had distant recurrence were included in the present study. We analyzed the association between SAR and mutations of 40 genes included in the five critical pathways of CRC (WNT, P53, RTK-RAS, TGF-ß, and PI3K). RESULTS: Mutation of genes within the WNT, P53, RTK-RAS, TGF-ß, and PI3K pathways were shown in 69(79.3%), 60(69.0%), 57(65.5%), 21(24.1%), and 19(21.8%) patients, respectively. Patients with TGF-ß pathway mutation were younger and had higher incidence of mucinous adenocarcinoma (MAC) histology and microsatellite instability-high. TGF-ß pathway mutation (median SAR of 21.6 vs. 44.4 months, p = 0.021) and MAC (20.0 vs. 44.4 months, p = 0.003) were associated with poor SAR, and receiving curative resection after recurrence was associated with favorable SAR (Not reached vs. 23.6 months, p <  0.001). Mutations in genes within other critical pathways were not associated with SAR. When MAC was excluded as a covariate, multivariate analysis revealed TGF-ß pathway mutation and curative resection after distant recurrence as an independent prognostic factor for SAR. The impact of TGF-ß pathway mutations were predicted using the PROVEAN, SIFT, and PolyPhen-2. Among 25 mutations, 23(92.0%)-24(96.0%) mutations were predicted to be damaging mutation. CONCLUSIONS: Mutation in genes within TGF-ß pathway may have negative prognostic role for SAR in CRC. Other pathway mutations were not associated with SAR.


Assuntos
Adenocarcinoma Mucinoso/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/genética , Transdução de Sinais/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Leucovorina/uso terapêutico , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Compostos Organoplatínicos/uso terapêutico , Cuidados Paliativos/métodos , Prognóstico , Reto/patologia , Reto/cirurgia , Análise de Sobrevida , Fator de Crescimento Transformador beta/metabolismo
20.
JAMA Oncol ; 5(7): 953-960, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31070690

RESUMO

Importance: Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study. Objective: To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion. Design, Setting, and Participants: This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months. Interventions: Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). Main Outcomes and Measures: The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. Results: For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]). Conclusions and Relevance: Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion. Trial Registration: ClinicalTrials.gov identifier: NCT02774187.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Veia Porta/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe/uso terapêutico , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intra-Arteriais , Leucovorina/uso terapêutico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Resultado do Tratamento , Adulto Jovem
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