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1.
BMC Gastroenterol ; 22(1): 341, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836104

RESUMO

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.


Assuntos
Neoplasias Colorretais , Síndrome Mão-Pé , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Neoplasias Colorretais/etiologia , Fluoruracila/efeitos adversos , Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/prevenção & controle , Humanos , Hidrocortisona/uso terapêutico , Oxaliplatina/efeitos adversos
2.
BMC Cancer ; 22(1): 789, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35850711

RESUMO

BACKGROUND: Distant metastasis has been the main failure pattern for locoregionally advanced rectal cancer (LARC) patients, and intensified neoadjuvant chemotherapy has become a popular research topic. The present study aimed to compare the survival outcomes, acute toxicities and surgical complications in LARC patients who received preoperative chemoradiotherapy with triweekly oxaliplatin and capecitabine (triweekly XELOX) or capecitabine. METHODS: Between 2007 and 2017, patients with clinically staged II-III rectal cancer who were treated with preoperative chemoradiotherapy using either triweekly XELOX (oxaliplatin 130 mg/m2 plus capecitabine 825 mg/m2) or capecitabine were included. Variables potentially influencing chemotherapy treatment selection were used to generate propensity scores (PS). The association between chemotherapy regimens and survival endpoints, including distant metastasis-free survival (DMFS), overall survival (OS) and disease-free survival (DFS), were evaluated and adjusted with PS. The acute toxicities and surgical complications were also compared. RESULTS: A total of 810 patients were included in the analysis; 277 (34.2%) patients received triweekly XELOX, and 533 (65.8%) received capecitabine. The pathological complete response (pCR) rates were 20.2 and 19.9% (P = 0.912) for the groups treated with triweekly XELOX and capecitabine, respectively. The 5-year DMFS, OS and DFS with triweekly XELOX versus capecitabine were 75.6% vs. 77.6% (P = 0.555), 79.2% vs. 83.3% (P = 0.101), and 69.9% vs. 73.7% (P = 0.283), respectively. Triweekly XELOX was not associated with an increased risk of severe toxicity during chemoradiotherapy, but it increased the risk of postoperative complications compared to capecitabine. After PS adjustment, the differences between the two groups remained insignificant in pCR rate, survival outcomes, and acute toxicities, and the difference in surgical complications disappeared. CONCLUSIONS: Triweekly XELOX or capecitabine concurrent with neoadjuvant radiotherapy leads to similar long-term survival outcomes, acute toxicities and surgical complications in LARC patients.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Quimiorradioterapia/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Oxaliplatina , Pontuação de Propensão , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia
3.
J Int Med Res ; 50(7): 3000605221110697, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35822291

RESUMO

OBJECTIVE: The UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the UGT1A1*28 polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy. METHODS: We analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for UGT1A1*28 and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m2. RESULTS: Six of the seven patients tolerated 120 mg/m2 irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed. CONCLUSIONS: mCRC patients homozygous for the UGT1A1*28 allele can tolerate irinotecan at an initial dose of 120 mg/m2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Glucuronosiltransferase , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/genética , Polimorfismo Genético
4.
JCO Precis Oncol ; 6: e2200180, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35862869

RESUMO

PURPOSE: Around 20%-30% of patients treated with fluoropyrimidines develop severe treatment-related adverse events (AEs). These are mainly caused by deficiency of dihydropyrimidine dehydrogenase, its main metabolizing enzyme. The DPYD*7 variant allele contains a frameshift mutation that leads to absence of dihydropyrimidine dehydrogenase. Clinical studies on this variant in patients treated with fluoropyrimidines are lacking because of its low minor allelic frequency. However, the DPYD*7 minor allelic frequency is 56-times higher in the Dutch compared with the global population. This allowed us to evaluate fluoropyrimidine tolerability in DPYD*7 variant allele carriers. MATERIALS AND METHODS: Patients treated with standard-of-care fluoropyrimidine who were pretreatment DPYD genotyped for DPYD*2A, *13, 2846A>T, and 1236G>A single-nucleotide polymorphisms were included for analyses. Patients were additionally screened for the DPYD*7 allele (rs72549309, 295-298delTCAT). AEs were graded if they worsened from baseline, according to Common Terminology Criteria for Adverse Events version 5.0. AEs ≥ grade 3 were considered severe. RESULTS: From 3,748 patients, we found 13 patients carrying heterozygous DPYD*7. Relevant clinical data were available for 11 patients. All patients developed fluoropyrimidine-related AEs, of which five patients developed severe AEs (46%). From these five patients, three patients were started with 65% or 50% of standard dose, but apparently still developed severe toxicity. Because of severe AEs, three patients discontinued treatment prematurely (one patient already started with 50% of standard dose) and one patient who started with 50% of standard dose was further reduced to 35% of standard dose. CONCLUSION: In this study, the clinical consequences of carrying the DPYD*7 variant allele were confirmed as 46% of the patients developed severe AEs, even in the presence of initial dose reductions. This underlines the need for prospective studies investigating the required fluoropyrimidine dose for DPYD*7 carriers.


Assuntos
Antimetabólitos Antineoplásicos , Di-Hidrouracila Desidrogenase (NADP) , Fluoruracila , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Di-Hidrouracila Desidrogenase (NADP)/genética , Fluoruracila/efeitos adversos , Humanos , Estudos Prospectivos
5.
ESMO Open ; 7(3): 100427, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35798468

RESUMO

BACKGROUND: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. PATIENTS AND METHODS: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. RESULTS: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). CONCLUSION: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.


Assuntos
Fluoruracila , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/efeitos adversos , Cardiotoxicidade/etiologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Adulto Jovem
6.
Anticancer Res ; 42(8): 3889-3894, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35896232

RESUMO

BACKGROUND/AIM: The regimen of nanoliposomal irinotecan plus 5-fluorouracil and leucovorin (Nal-IRI/FL) was approved in Japan as second-line chemotherapy after gemcitabine-based treatment for pancreatic ductal adenocarcinoma (PDAC) in 2020. We examined the difference in outcome between patients treated with second-line folinic acid, fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX) and those treated with nal-IRI/FL after first-line gemcitabine and nab-paclitaxel (GnP). PATIENTS AND METHODS: The outcomes of 34 patients with PDAC who received second-line FOLFIRINOX (n=21) or nal-IRI/FL (n=13) after GnP at our Department from January 2016 to June 2021 were reviewed retrospectively. RESULTS: Patient backgrounds did not differ between the groups. Dose reduction was more frequently required for treatment with FOLFIRINOX than with nal-IRI/FL (86% vs. 46%, p=0.022). Pegfilgrastim and aprepitant were used more frequently in the FOLFIRINOX group (both p<0.01). Progression-free survival (5.9 vs. 8.3 months) and overall survival (9.1 vs. 11.2 months) did not differ significantly between the groups. The frequency of grade 3 (Common Terminology Criteria for Adverse Events) or higher adverse events was similar between the groups. All-grade peripheral neuropathy was more common in the FOLFIRINOX group (100% vs. 77%, p=0.048). CONCLUSION: FOLFIRINOX and nal-IRI/FL as second-line therapy after GnP provided similar prognoses, although supportive treatment and dose reduction were more frequently required for FOLFIRINOX.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/etiologia , Desoxicitidina/análogos & derivados , Fluoruracila/efeitos adversos , Humanos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Oxaliplatina/efeitos adversos , Paclitaxel , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos
7.
Clin Nutr ; 41(7): 1600-1604, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35671612

RESUMO

BACKGROUND & AIMS: Patients with colon cancer who prematurely discontinue postoperative chemotherapy may have an increased risk of disease recurrence and death. This study tested the hypothesis that the quantity and distribution of abdominal adipose tissue predict premature chemotherapy discontinuation. METHODS: This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 24-weeks of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposures were body mass index (BMI) and computed tomography-derived abdominal adiposity measures (e.g., visceral, subcutaneous, and intramuscular adipose tissue). The primary endpoint was premature chemotherapy discontinuation, defined as receiving <6 cycles of FOLFOX. Generalized linear models quantified the relative risk (RR) of premature chemotherapy discontinuation adjusted for age, sex, cancer stage, height, and muscle area, using two-sided statistical tests. RESULTS: Forty-two patients [7.9% (95% CI: 5.7, 10.5)] prematurely discontinued chemotherapy. Visceral adipose tissue [RR: 3.27 (95% CI: 1.26, 8.49)] and intramuscular adipose tissue [RR: 2.79 (95% CI: 1.09, 7.12)] were statistically significantly associated with an increased risk of premature chemotherapy discontinuation. BMI [RR: 2.07 (95% CI: 0.75, 5.73)] and subcutaneous adipose tissue [RR: 2.32 (95% CI: 0.91, 5.94)] were not statistically significantly associated with premature chemotherapy discontinuation. CONCLUSION: Among patients with stage II-III colon cancer who initiate postoperative chemotherapy, excess visceral and intramuscular adiposity may be risk factors for the premature discontinuation of chemotherapy.


Assuntos
Adiposidade , Neoplasias do Colo , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Obesidade Abdominal , Oxaliplatina/uso terapêutico
8.
PLoS One ; 17(6): e0269399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35657983

RESUMO

BACKGROUND: The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice. MATERIALS AND METHODS: We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group. RESULTS: Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively). CONCLUSIONS: FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Oxaliplatina , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , Neoplasias Retais/tratamento farmacológico , Estudos Retrospectivos
9.
Med Sci Monit ; 28: e937136, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35718990

RESUMO

BACKGROUND Studies are ongoing to determine the optimal adjuvant chemotherapy (ACT) for resected pancreatic carcinoma (PC). FOLFIRINOX is a chemotherapy regimen including oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil (5-FU). S-1 is a fluoropyrimidine derivative widely used as ACT for gastrointestinal malignancy. This single-center retrospective study aimed to compare the efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) with S-1 as ACT for resected PC. MATERIAL AND METHODS A total of 71 patients with PC who accepted ACT after R0 resection between February 2016 and January 2019 were enrolled in this retrospective study. Among these patients, 34 received mFOLFIRINOX regimen chemotherapy (mFFX group), while 37 received S-1 monochemotherapy (S-1 group). The mFOLFIRINOX regimen included oxaliplatin 65 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m², 5-FU 400 mg/m², and continuous 5-FU 2400 mg/m² (for 46 h), in a 2-week schedule. The S-1 monochemotherapy (80-120 mg/day according to body surface area [BSA], in 2 divided doses for 2 week) was administrated every 3 weeks. We followed up these patients and analyzed the relapse-free survival (RFS), overall survival (OS), and chemotherapy-induced adverse events (AEs). RESULTS The mFFX group demonstrated a markedly higher 3-year RFS (P=0.0332) and OS (P=0.0346) than the S-1 group. Patients in the mFFX group experienced significantly more common and severe thrombocytopenia (P=0.0372), fatigue (P=0.0226), nausea/vomiting (P=0.0337), and diarrhea (P=0.0018). No chemotherapy-induced death was documented. CONCLUSIONS This retrospective study indicated that if dose adjustment and adverse events management are properly administrated, mFOLFIRINOX regimen chemotherapy could result in an improved survival compared with S-1 monochemotherapy for resected PC.


Assuntos
Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Fluoruracila/efeitos adversos , Humanos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos
10.
Integr Cancer Ther ; 21: 15347354221105498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35695002

RESUMO

BACKGROUND: Colorectal cancer is the third most common malignant disease and the second leading cause of death worldwide. Previous studies showed improved bioavailability and cytotoxicity of ginsenoside-modified nanostructured lipid carrier containing curcumin (G-NLC) in human colon cancer cell lines. This study aimed to evaluate the safety and tolerability with long-term survival rates in patients with colorectal cancer with unresectable metastases after treatment with first-line bevacizumab/FOLFIRI (folinic acid, bolus/continuous fluorouracil, and irinotecan) in combination with a dietary supplement of G-NLC. METHODS: This study was a prospective, observational, single-group analysis. The enrolled patients had colorectal cancer with unresectable metastases and were administered bevacizumab and FOLFIRI in combination with daily oral G-NLC as first-line treatment. Overall survival, progression-free survival, tumor response, and adverse events were evaluated. RESULTS: A total of 44 patients were enrolled between 2015 and 2019. The median age was 65 (range 45-81) years and the sex ratio was 31:13 (male:female). The primary tumor locations were the colon (31 patients) and rectum (13 patients). The metastatic sites included, liver only (n = 20), lung only (n = 6), both liver and lung (n = 12), and others (n = 6). The median duration of curcumin supply was 7.9 (range 0.9-16.6) months. The most common grade 3 or higher adverse events were neutropenia (n = 15, 34.1%), followed by nausea (n = 4, 9.1%) and vomiting (n = 4, 9.1%). Within the median follow-up period of 22.8 months, the median overall survival was 30.7 months, and the median progression-free survival was 12.8 months. None of the patients achieved complete response (CR); however, 9 patients showed partial response (PR), and 3 patients underwent conversion surgery. CONCLUSIONS: Bevacizumab/FOLFIRI with G-NLC as first-line chemotherapy in patients with colorectal cancer with unresectable metastases presented comparable long-term survival outcomes with acceptable toxicity outcomes. Additional randomized controlled studies are needed to establish definitive conclusions regarding this new regimen for metastatic colorectal cancer.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Curcumina , Ginsenosídeos , Neoplasias Retais , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/efeitos adversos , Camptotecina/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Curcumina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Ginsenosídeos/uso terapêutico , Humanos , Lipídeos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Recenti Prog Med ; 113(6): 19e-24e, 2022 06.
Artigo em Italiano | MEDLINE | ID: mdl-35758127

RESUMO

Cetuximab in combination with chemotherapy is a standard first-line treatment regimen for patients with metastatic colorectal cancer (mCRC) RAS wild-type (wt); however, the efficacy of cetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX) had never been demonstrated in a prospective, randomized, controlled phase III study. The TAILOR study is the first randomized, multicenter, prospective Phase III study evaluating the addition of cetuximab to FOLFOX in a RAS wt Chinese population and thus providing confirmatory data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Metástase Neoplásica/tratamento farmacológico , Compostos Organoplatínicos/efeitos adversos , Estudos Prospectivos , Neoplasias Retais/induzido quimicamente , Neoplasias Retais/tratamento farmacológico
12.
Integr Cancer Ther ; 21: 15347354221105485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686441

RESUMO

BACKGROUND: Chemotherapy-induced adverse effects (CIAEs) remain a challenging problem due to their high incidences and negative impacts on treatment in Chinese colorectal cancer (CRC) patients. We aimed to identify risk factors and predictive markers for CIAEs using food/nutrition data in CRC patients receiving post-operative capecitabine-based chemotherapy. METHODS: Food/nutrition data from 130 Chinese CRC patients were analyzed. Univariate and multivariate analyses were used to identify CIAE-related food/nutrition factors. Prediction models were constructed based on the combination of these factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability of models. RESULTS: A total of 20 food/nutrition factors associated with CIAEs were identified in the univariate analysis after adjustments for total energy and potential confounding factors. Based on multivariate analysis, we found that, among these factors, dessert, eggs, poultry, and milk were associated with several CIAEs. Most importantly, poultry was an overall protective factor; milk and egg were risk factors for hand-foot syndrome (HFS) and bone marrow suppression (BMS), respectively. Developed multivariate models in predicting grade 1 to 3 CIAEs and grade 2/3 CIAEs both had good discrimination (AUROC values from 0.671 to 0.778, 0.750 to 0.946 respectively), which had potential clinical application value in the early prediction of CIAEs, especially for more severe CIAEs. CONCLUSIONS: Our findings suggest that patients with high milk and egg intakes should be clinically instructed to control their corresponding dietary intake to reduce the likelihood of developing HFS and BMS during capecitabine-based chemotherapy, respectively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03030508.


Assuntos
Antimetabólitos Antineoplásicos , Capecitabina , Neoplasias Colorretais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , China/epidemiologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Ovos , Fluoruracila/efeitos adversos , Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Humanos , Leite , Fatores de Risco
13.
Exp Oncol ; 44(1): 60-66, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35548958

RESUMO

BACKGROUND: Side effects of chemotherapy in cancer patients need to be investigated in more detail. AIM: To determine the incidence of cardiotoxicity in patients treated with different chemotherapy regimens containing 5-fluorouracil (5-FU) in Zanjan, Iran. PATIENTS AND METHODS: In a prospective cohort study, patients with different types of solid gastrointestinal tumors who were candidates for 5-FU based chemotherapy regimens were enrolled. The study population consisted of 100 patients (48 females and 52 males) with a mean age of 63.99 ± 12.40 years. We measured serum cardiac troponin I (cTnI) levels before and during each chemotherapy cycle and determined the occurrence of cardiotoxicity in patients based on the levels of cTnI, clinical signs and symptoms as well as electrocardiogram findings. In addition, we assessed a history of diabetes, hypertension, smoking, dyslipidemia and previous chest radiation as potential risk factors for cardiotoxicity. RESULTS: The incidence of cardiotoxicity was 8%, of which 5 patients were diagnosed with acute coronary syndrome, 2 patients with arrhythmias and one with hypotension. In addition, there was no significant association between studied risk factors and 5-FU induced cardiotoxicity. CONCLUSION: The incidence of cardiotoxicity in patients receiving 5-FU infusion regimens was notable. Thus, paying more attention to the 5-FU-induced cardiotoxicity is necessary in order to improve the prognosis of patients with cancer.


Assuntos
Fluoruracila , Neoplasias , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Estudos Prospectivos
14.
J Egypt Natl Canc Inst ; 34(1): 22, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35599280

RESUMO

BACKGROUND: The administration of 5-fluorouracil (5FU) in the treatment of gastrointestinal (GI) malignancies is associated with common side effects such as mucositis, diarrhoea, and myelosuppression, which are easily managed with supportive measures and dose adjustments. Cardiotoxicity and neurotoxicity are rare but reversible side effects of 5-FU and are treated with withdrawal of the drug and conservative measures. The presenting symptoms of 5-FU-induced leukoencephalopathy are often confusing and pose a diagnostic dilemma in routine clinical practice. METHODS: We report a series of five patients with GI malignancies who developed 5-FU-induced leukoencephalopathy. RESULTS: All (n = 5) had Naranjo scores of 6-7, predictive of 5-FU-related adverse effects, with clinical and radiological findings suggestive of 5-FU-induced encephalopathy as described in prior literature. The median time to onset of symptoms from initiation of 5FU was 3 days (range: 2-4 days). All patients improved after conservative management with complete neurological recovery. CONCLUSION: Prompt recognition of this rare yet severe adverse effect of 5-FU-based chemotherapy aids early withdrawal of the offending agent (5-FU) and timely initiation of supportive measures and helps plan alternative oncological interventions.


Assuntos
Leucoencefalopatias , Neoplasias , Antimetabólitos Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/tratamento farmacológico , Neoplasias/tratamento farmacológico
15.
Acta Cir Bras ; 37(2): e370204, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507968

RESUMO

PURPOSE: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. METHODS: PCCL was orally administered at a dose of 20 mg·kg-1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg-1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. RESULTS: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. CONCLUSIONS: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.


Assuntos
Cuscuta , Mucosite , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Peso Corporal , Caspase 3/metabolismo , Cuscuta/metabolismo , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/patologia , Fluoruracila/efeitos adversos , Mucosa Intestinal/patologia , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Sementes , Proteína X Associada a bcl-2/metabolismo
16.
Oxid Med Cell Longev ; 2022: 7255497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35585883

RESUMO

Chemotherapy-induced intestinal mucositis (CIM) is a significant dose-limiting adverse reaction brought on by the cancer treatment. Multiple studies reported that reactive oxygen species (ROS) is rapidly produced during the initial stages of chemotherapy, when the drugs elicit direct damage to intestinal mucosal cells, which, in turn, results in necrosis, mitochondrial dysfunction, and ROS production. However, the mechanism behind the intestinal redox system-based induction of intestinal mucosal injury and necrosis of CIM is still undetermined. In this article, we summarized relevant information regarding the intestinal redox system, including the composition and regulation of redox enzymes, ROS generation, and its regulation in the intestine. We innovatively proposed the intestinal redox "Tai Chi" theory and revealed its significance in the pathogenesis of CIM. We also conducted an extensive review of the English language-based literatures involving oxidative stress (OS) and its involvement in the pathological mechanisms of CIM. From the date of inception till July 31, 2021, 51 related articles were selected. Based on our analysis of these articles, only five chemotherapeutic drugs, namely, MTX, 5-FU, cisplatin, CPT-11, and oxaliplatin were shown to trigger the ROS-based pathological mechanisms of CIM. We also discussed the redox system-mediated modulation of CIM pathogenesis via elaboration of the relationship between chemotherapeutic drugs and the redox system. It is our belief that this overview of the intestinal redox system and its role in CIM pathogenesis will greatly enhance research direction and improve CIM management in the future.


Assuntos
Antineoplásicos , Mucosite , Antineoplásicos/uso terapêutico , Fluoruracila/efeitos adversos , Humanos , Mucosa Intestinal/metabolismo , Intestinos/patologia , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/patologia , Necrose/tratamento farmacológico , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
17.
Future Oncol ; 18(21): 2643-2653, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35608115

RESUMO

Aim: Comparison of first-line FOLFIRINOX (FFN) and nab-paclitaxel plus gemcitabine (NabGem) in patients with metastatic pancreatic ductal adenocarcinoma. Patients & methods: The authors analyzed data from 160 patients with metastatic pancreatic adenocarcinoma receiving first-line FFN (n = 43) or NabGem (n = 117). Results: FFN and NabGem were similar in median progression-free survival (24.43 vs 26.28 weeks; hazard ratio [HR]: 0.88) and medial overall survival (47.43 vs 42.86 weeks; HR: 0.90). Of the 43 patients receiving FFN, 26 (60.4%) were treated with second-line NabGem; 14/117 (12.0%) patients receiving NabGem received second-line FFN (p < 0.0001). In the FFN → NabGem and NabGem → FFN groups, median overall survival was 51.2 and 71.6 weeks (HR: 0.69; p = 0.15). In patients receiving NabGem, second-line FFN, compared with FOLFOX/CAPOX or FOLFIRI, improved median progression-free survival 2 (25.6 vs 12.1 weeks; HR: 0.47; p = 0.0067) and median overall survival 2 (39.0 vs 19.14 weeks; HR: 0.49; p = 0.032). Conclusion: First-line FFN and NabGem promote similar clinical outcomes. Second-line FFN should be considered after NabGem.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/etiologia , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina/efeitos adversos , Oxaliplatina , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/patologia
18.
Biochem Biophys Res Commun ; 614: 34-40, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35567942

RESUMO

5-Fluorouracil (5-FU) is a chemotherapy drug used to treat tumors. Previous studies have shown that Akkermansia muciniphila (A. muciniphila) and its outer membrane protein, Amuc_1100, alleviate dextran sodium sulfate (DSS)-induced colitis in mice. We investigated the effects of both A. muciniphila and Amuc_1100 on 5-FU-induced intestinal mucosal damage in mice. C57BL/6 mice were gavaged with A. muciniphila or Amuc_1100 daily before, during, and after 5-FU injection for a total of 14 days. By evaluating diarrheal toxicity scores, body weight changes, colonic anatomy images, and histopathology of intestinal injury in these mice, we found that A. muciniphila and Amuc_1100 alleviated 5-FU-induced intestinal mucositis. Quantitative polymerase chain reaction assays of intestinal cytokine mRNA levels demonstrated that both A. muciniphila and Amuc_1100 attenuated the upregulation of intestinal Tumor Necrosis Factor-α (TNF-α) and interleukin-6 (IL-6) induced by 5-FU treatment. In addition, they both reduced 5-FU-induced the NLR family pyrin domain containing 3 (NLRP3) inflammatory vesicle activation. Furthermore, by monitoring the mRNA expression of tight junction proteins in the intestine, we found that A. muciniphila and Amuc_1100 were capable of restoring the damaged intestinal barrier. Notably, A. muciniphila and Amuc_1100 also played a role in altering the structure of the intestinal microbial community. The present study revealed the protective role of both A. muciniphila and Amuc_1100 in the intestinal mucositis caused by 5-FU, providing new insights into treatment options.


Assuntos
Mucosite , Akkermansia , Animais , Fluoruracila/efeitos adversos , Mucosa Intestinal , Intestinos , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , RNA Mensageiro , Verrucomicrobia
19.
Future Oncol ; 18(20): 2465-2473, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35535555

RESUMO

Standard-of-care for resectable gastric/gastroesophageal junction cancer includes surgery and neoadjuvant-adjuvant 5-fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) chemotherapy. Early-phase clinical studies support further clinical development of the immune checkpoint inhibitor (ICI); durvalumab, an anti-PD-L1 antibody, in patients with gastric/gastroesophageal junction cancer. Accumulating evidence indicates that ICIs combined with FLOT chemotherapy improve clinical outcomes in patients with advanced or metastatic cancer. We describe the rationale for and the design of MATTERHORN, a randomized, double-blind, placebo-controlled, phase III study investigating the efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy followed by adjuvant durvalumab monotherapy in patients with resectable gastric/gastroesophageal junction cancer. The planned sample size is 900 patients, the primary end point is event-free survival and safety and tolerability will be evaluated. Clinical trial registration: NCT04592913 (ClinicalTrials.gov).


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Junção Esofagogástrica/patologia , Fluoruracila/efeitos adversos , Humanos , Terapia Neoadjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/patologia
20.
J Cancer Res Clin Oncol ; 148(8): 2153-2162, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35622166

RESUMO

PURPOSE: The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. METHOD: Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 µL of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. RESULTS: The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. CONCLUSION: The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.


Assuntos
Mucosite , Estomatite , Syzygium , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/farmacologia , Fluoruracila/efeitos adversos , Géis/efeitos adversos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Extratos Vegetais/efeitos adversos , Ratos , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Estomatite/prevenção & controle
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