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1.
Cancer Treat Rev ; 96: 102177, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33798955

RESUMO

A few months ago, results from two randomised phase III trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were presented (RAPIDO and PRODIGE 23), consistently showing better short- and long-term outcomes with TNT as compared with standard neoadjuvant long-course chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). These results represent corroborating evidence in support of a practice that many centres had already implemented based on promising preliminary data. Also, they provide new, high-level evidence to endorse TNT as a new management option in the treatment algorithm of stage II-III rectal cancer in those centres where CRT and SCRT have long remained the only accepted standard neoadjuvant treatments. Having two consistently positive trials is certainly reassuring regarding the potential of TNT as a general treatment approach. Nevertheless, substantial differences between these trials pose important challenges in relation to the generalisability and applicability of their results, and translation of the same into practical clinical recommendations. In this article, we address a number of key questions that the RAPIDO and PRODIGE 23 trials have raised among the broad community of gastrointestinal oncologists, proposing an interpretation of the data that may help the decision making, and highlighting grey areas that warrant further investigation.


Assuntos
Neoplasias Retais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/administração & dosagem , Quimiorradioterapia/métodos , Ensaios Clínicos Fase III como Assunto , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Terapia Neoadjuvante , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/patologia
2.
BMC Surg ; 21(1): 35, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33435947

RESUMO

BACKGROUND: Guidelines do not recommend surgery for patients with oligometastatic disease from esophagogastric adenocarcinoma (EGAC), although some studies suggest a more favorable survival. We analyzed the outcome of oligometastatic EGAC receiving FLOT chemotherapy followed by surgery. METHODS: The data of patients with either pre-therapeutic, post-neoadjuvant or intraoperative clinical diagnosis of oligometastatic EGAC were extracted from a prospective database of the 2009-2018 treatment period. 48 consecutive patients were identified with oligometastatic disease, who underwent perioperative chemotherapy plus surgery. We retrospectively analyzed surgical outcome and overall survival. RESULTS: The overall 5-year survival was 18%. 12 patients (25%) with pre-therapeutic oligometastatic EGAC, who had no histologic vital tumor evidence of metastases after surgery had a survival rate of 48% compared to an 11% 5-year survival rate of 36 patients (75%), who had histologic vital tumor metastatic evidence after FLOT chemotherapy and surgical resection (p = 0.012). The survival rates after R0, R1 and R2 (non-resected metastases) resection were 21% (n = 33), 0% (n = 4) and 17% (n = 11), respectively (p = 0.273). CONCLUSION: Oligometastatic EGAC is associated with poor overall survival even after complete resection of all tumor manifestations. The subgroup of patients with a complete histologic response of metastatic lesions to neoadjuvant FLOT shows 5-year survival rates similar to non-metastatic EGAC. Trial registration Not applicable.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Junção Esofagogástrica , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
3.
Anticancer Res ; 40(9): 5263-5270, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878815

RESUMO

BACKGROUND: Treatment for platinum-resistant ovarian cancer is difficult and challenging because available chemotherapeutic agents only offer short survival improvements. The efficacy of re-treatment with platinum-based agents including nedaplatin for platinum-resistant patients has not been fully investigated. CASE REPORT: We describe herein three cases of heavily treated platinum-resistant ovarian cancer that were successfully treated with weekly nedaplatin followed by olaparib. After becoming platinum-resistant, the cases were treated with non-platinum chemotherapies. Following these regimens, weekly nedaplatin was introduced, followed by olaparib. At the time of writing, survival since the start of weekly nedaplatin was 30 months for case 1, 20 months for case 2, and 17 months for case 3, with all patients showing no evidence of disease. CONCLUSION: Weekly nedaplatin followed by olaparib might represent a good treatment option for platinum-resistant ovarian cancer and is a solid candidate for further evaluation.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Biópsia , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/diagnóstico , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Breast Cancer Res ; 22(1): 79, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711554

RESUMO

BACKGROUND: We previously showed that BRCA-like profiles can be used to preselect individuals with the highest risk of carrying BRCA mutations but could also indicate which patients would benefit from double-strand break inducing chemotherapy. A simple, robust, and reliable assay for clinical use that utilizes limited amounts of formalin-fixed, paraffin-embedded tumor tissue to assess BRCAness status in both ER-positive and ER-negative breast cancer (BC) is currently lacking. METHODS: A digital multiplex ligation-dependent probe amplification (digitalMLPA) assay was designed to detect copy number alterations required for the classification of BRCA1-like and BRCA2-like BC. The BRCA1-like classifier was trained on 71 tumors, enriched for triple-negative BC; the BRCA2-like classifier was trained on 55 tumors, enriched for luminal-type BC. A shrunken centroid-based classifier was developed and applied on an independent validation cohort. A total of 114 cases of a randomized controlled trial were analyzed, and the association of the classifier result with intensified platinum-based chemotherapy response was assessed. RESULTS: The digitalMLPA BRCA1-like classifier correctly classified 91% of the BRCA1-like samples and 82% of the BRCA2-like samples. Patients with a BRCA-like tumor derived significant benefit of high-dose chemotherapy (adjusted hazard ratio (HR) 0.12, 95% CI 0.04-0.44) which was not observed in non-BRCA-like patients (HR 0.9, 95% CI 0.37-2.18) (p = 0.01). Analysis stratified for ER status showed borderline significance. CONCLUSIONS: The digitalMLPA is a reliable method to detect a BRCA1- and BRCA2-like pattern on clinical samples and predicts platinum-based chemotherapy benefit in both triple-negative and luminal-type BC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Biomarcadores Tumorais/genética , Variações do Número de Cópias de DNA , Feminino , Seguimentos , Humanos , Técnicas de Amplificação de Ácido Nucleico , Compostos Organoplatínicos/administração & dosagem , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
5.
Anticancer Res ; 40(8): 4263-4270, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727753

RESUMO

BACKGROUND/AIM: Enzymatic variants involved in fluoropyrimidine metabolism have been associated with adverse events (AEs). We assessed the association between C677T (rs1801133) and A1298 (rs1801131) methylenetetrahydrofolate reductase (MTHFR) polymorphisms and AEs in patients with first-line fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Fifty patients with metastatic colorectal cancer were prospectively followed-up during the first 4 cycles of fluoropyrimidine-based treatment to assess AEs. Germline DNA was analyzed to determine the C677T and A1298C MTHFR polymorphisms. The associations between MTHFR polymorphisms and toxicity were examined. RESULTS: Individuals carrying at least one mutant allele of the MTHFR C677T polymorphism had increased risk to experience anemia (OR=1.69, 95% CI=1.13-2.53, p=0.005), neutropenia (OR=2.27, 95% CI=1.47-3.42, p<0.001) thrombocytopenia (OR=1.91, 95% CI=1.30-2.70, p<0.001), neuropathy (OR=1.77, 95% CI=1.16-2.70, p=0.02), diarrhea (OR=1.69, 95% CI=1.13-2.53, p=0.005), and hand-foot syndrome (OR=1.56, 95% CI=1.08-2.27, p=0.013), compared to patients carrying the wild type alleles. The presence of the mutant allele C of the MTHFR A1298C polymorphism was associated with increased risk of anemia (OR=2.75, 95% CI=1.01-7.48, p=0.02) and thrombocytopenia (OR=3.14, 95% CI=1.01-9.78, p=0.03); however, the prevalence of this allele in the sample was quite low (20%). CONCLUSION: MTHFR C677T and A1298C polymorphisms predicted toxicity in a subset of Mestizo patients with colorectal adenocarcinoma.


Assuntos
Antimetabólitos Antineoplásicos/toxicidade , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Grupos Étnicos/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Idoso , Neoplasias Colorretais/patologia , Costa Rica , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Estudos Prospectivos
6.
J Cancer Res Ther ; 16(3): 686-689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719293

RESUMO

Central nervous damage related to intra-arterial infusion chemotherapy (IAC) for head and neck cancer reported to date are cerebral infarction, transient ischemic attack, and neuropathy. There have been no reports of cerebral hemorrhage as an IAC-related complication for head and neck cancer. Authors report a case that underwent intra-arterial infusion chemoradiotherapy for advanced sphenoid sinus cancer which extended to the left cavernous sinus and cranium, subsequently suffered cerebral hemorrhage thought to have been caused by IAC. Treatment should be performed with greater caution when the head and neck cancer involves the cavernous sinus or cranium, as in the present case.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hemorragia Cerebral/etiologia , Neoplasias dos Seios Paranasais/tratamento farmacológico , Seio Esfenoidal/patologia , Idoso , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/patologia , Quimiorradioterapia , Docetaxel/administração & dosagem , Feminino , Humanos , Infusões Intra-Arteriais , Compostos Organoplatínicos/administração & dosagem , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/radioterapia , Prognóstico
7.
Anticancer Res ; 40(7): 3925-3929, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620633

RESUMO

BACKGROUND/AIM: CHORUS and EORTC55971 trials demonstrated that neoadjuvant chemotherapy followed by interval debulking surgery (IDS) or primary debulking surgery (PDS) offered the same survival rates. These trials have since been criticised due to poor surgical complexity. We compared overall (OS), progression free (PFS), and platinum sensitivity in advanced ovarian cancer (AOC) patients undergoing IDS or PDS, who had received either intermediate or high complexity surgery to achieve complete cytoreduction. PATIENTS AND METHODS: All patients with AOC treated between February 2014 and May 2019 obtaining complete cytoreduction with intermediate/high surgical complexity were included. Recurrence was defined according to GCIG criteria on radiological findings and/or CA125 levels. RESULTS: Seventy-one patients (38 PDS and 33 IDS) with full recurrence data were identified. No statistical difference was seen between groups in OS, PFS or platinum sensitive interval. CONCLUSION: PDS or IDS were both acceptable treatment options for AOC, showing similar survival and platinum sensitivity outcomes in patients undergoing intermediate or high complexity surgery.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Idoso , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Ovarianas/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida
8.
J Cancer Res Clin Oncol ; 146(10): 2559-2574, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681294

RESUMO

PURPOSE: Canonical Wnt/ ß-catenin pathway is one mechanism being activated in platinum-resistant epithelial ovarian cancer (EOC). Detecting potential targets for Wnt pathway modulation as a putative future therapeutic approach was the aim of this study. METHODS: Biological effects of different Wnt modulators (SB216763, XAV939 and triptolide) on the EOC cell lines A2780 and its platinum-resistant clone A2780cis were investigated via multiple functional tests. Immunohistochemistry (IHC) was carried out to compare the expression levels of Wnt marker proteins (ß-catenin, snail/ slug, E-cadherin) in patient specimens and to correlate them with lifetime data. RESULTS: We could show that activated Wnt signaling of the platinum-resistant EOC cell line A2780cis can be reversed by Wnt manipulators through SB216763 or XAV939. All Wnt manipulators tested consecutively decreased cell proliferation and cell viability. Apoptosis of A2780 and A2780cis was enhanced by triptolide in a dose-dependent manner, whereas cell migration was inhibited by SB216763 and triptolide. IHC analyses elucidated significantly different expression patterns for Wnt markers in the serous subtype. Herein, higher plasmatic snail/ slug expression is associated with improved progression-free (PFS) and overall survival (OS). CONCLUSION: According to the described effects on EOC biology, all three Wnt manipulators seem to have the potential to augment the impact of a platinum-based chemotherapy in EOC. This is promising as a dominance of this pathway was confirmed in serous histology.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/metabolismo , Compostos Organoplatínicos/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Antígenos CD/biossíntese , Antígenos CD/metabolismo , Caderinas/biossíntese , Caderinas/metabolismo , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Diterpenos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Compostos de Epóxi/farmacologia , Feminino , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Indóis/farmacologia , Maleimidas/farmacologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/patologia , Fenantrenos/farmacologia , beta Catenina/biossíntese , beta Catenina/metabolismo
9.
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
10.
J Cancer Res Clin Oncol ; 146(10): 2681-2691, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449003

RESUMO

PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Panitumumabe/administração & dosagem , Resultado do Tratamento , Proteínas ras/genética
11.
Oncology ; 98(9): 630-636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428899

RESUMO

OBJECTIVE: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. METHODS: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. RESULTS: Twenty-two and nine patients received nivolumab as third-line and fourth- to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. CONCLUSION: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Nivolumabe/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Feminino , Humanos , Irinotecano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Pirrolidinas/administração & dosagem , Estudos Retrospectivos , Terapia de Salvação/métodos , Neoplasias Gástricas/diagnóstico por imagem , Timina/administração & dosagem
12.
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
15.
J Cardiothorac Surg ; 15(1): 52, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32228632

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma with tumor thrombus in the arch of the azygos vein has not been reported to date. Neoadjuvant chemotherapy can decrease the stage in patients with advanced preoperative tumor staging, regaining surgical opportunities and significantly prolonging progression-free survival and overall survival. Herein, we present a case of esophageal squamous cell carcinoma accompanied by tumor thrombus in the arch of the azygos vein, and the patient underwent radical surgery after neoadjuvant chemotherapy. CASE PRESENTATION: A 63-year-old male with esophageal squamous cell carcinoma was found to have tumor thrombus formation in the arch of the azygos vein. Four courses of neoadjuvant chemotherapy with the TP regimen (paclitaxel plus nedaplatin) were given. Reexamination revealed a significant reduction in tumor and tumor thrombus volume. Therefore, McKeown radical resection for esophageal cancer and removal of the tumor thrombus in the arch of the azygos vein were performed. Postoperative pathology suggested complete remission of the esophageal tumor and the presence of small focal cancer tissues in the arch of the azygos vein. CONCLUSION: We report a case of esophageal squamous cell carcinoma with tumor thrombus formation in the azygos vein. We conducted radical resection after 4 rounds of neoadjuvant chemotherapy, and the pathological results revealed complete remission of the tumor. We report our experience addressing this rare case, and we hope to find the underlying mechanism of tumor thrombus formation and whether it has any effects on prognosis in our future study.


Assuntos
Veia Ázigos/cirurgia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Trombose/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/complicações , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Esofagectomia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Paclitaxel/administração & dosagem , Trombose/etiologia
16.
Lancet Oncol ; 21(4): 497-507, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32164906

RESUMO

BACKGROUND: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. METHODS: TRIBE2 was an open-label, phase 3, randomised study of patients aged 18-75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov, NCT02339116. FINDINGS: Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1-41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3-21·4) in the experimental group and 16·4 months (15·1-17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63-0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3-4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). INTERPRETATION: Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. FUNDING: The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann-La Roche.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Adolescente , Adulto , Idoso , Camptotecina/administração & dosagem , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Adulto Jovem
17.
PLoS One ; 15(3): e0229900, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142532

RESUMO

BACKGROUND: In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed. METHODS: An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS. RESULTS: Phase-A enrolled 128 patients; median age was 64 years (range: 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI: 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI: 7.9-10.8) for Phase-A and 6.7 months (95% CI: 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI: 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group. CONCLUSIONS: Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01588990; posted May 1, 2012.


Assuntos
Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Inflamação/tratamento farmacológico , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/efeitos adversos , Biomarcadores Tumorais/genética , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Inflamação/genética , Inflamação/patologia , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Oxaloacetatos/administração & dosagem , Pesquisa Médica Translacional
18.
Yakugaku Zasshi ; 140(3): 449-453, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32115568

RESUMO

Herein, we investigated the pharmacokinetic (PK) profile of nedaplatin (cis-diamine-glycolateplatinum; CDGP) in a hemodialysis (HD) patient with advanced esophageal squamous cell carcinoma (ESCC) by administering the CDGP immediately prior to HD. Our patient was treated with CDGP (45 mg/m2 for a total dose of 60.2 mg) and 5-fluorouracil (560 mg/m2 for a total dose of 750 mg) before initiating HD. The total platinum (Pt) concentration (Pt_total) and free Pt concentration (Pt_free) 2 h after completion of HD were 0.4 µg/mL and 0.3 µg/mL, respectively. The removal rates of Pt_total and Pt_free by the dialyzer were 76.5% and 84.6%, respectively. Twenty-four hours after CDGP administration, the Pt_free was below the detection limit of the method of analysis. Pt_free within the range of the recommended CDGP target AUC0-24 was 8-10 µg/mL•h, the AUC0-24 of Pt_total and Pt_free were 16.5 µg/mL•h and 8.8 µg/mL•h, respectively. We conclude that HD should be performed after the end of CDGP infusion as part of the CDGP chemotherapy regimen for HD patients with ESCC, and suggest that HD is effective for obtaining a PK profile of CDGP similar to patients with normal renal function.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Compostos Organoplatínicos/farmacocinética , Diálise Renal , Idoso , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Feminino , Fluoruracila/administração & dosagem , Humanos , Compostos Organoplatínicos/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
19.
Cancer Radiother ; 24(2): 88-92, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32156457

RESUMO

PURPOSE: The optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60Gy delivered with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: All consecutive patients that received a definitive CRT>50Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis. RESULTS: A total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60Gy (54-66) and 48Gy (44.8-56) delivered in 30 (27-35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4Gy (IC 95%: 4.8-19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0-46.0) and 4.6% (0.7-19.8) respectively. The mean dose delivered to the heart was 13.9Gy (IC 95%:0.3-31.3) with a median V40 of 3.3% (0.0-25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9-4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%). CONCLUSION: We demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Tolerância a Radiação , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Estenose Esofágica/etiologia , Feminino , Fluoruracila/administração & dosagem , Coração/efeitos da radiação , Humanos , Leucovorina/administração & dosagem , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Órgãos em Risco/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
20.
BMJ Case Rep ; 13(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32139448

RESUMO

A 49-year-old male carcinoma rectum patient was treated with neoadjuvant FOLFOX (folinic acid, fluorouracil (5-FU) and oxaliplatin) chemotherapy, chemoradiotherapy with capecitabine, surgery and adjuvant FOLFOX. On follow-up, the patient developed a metabolically active liver lesion mimicking metastasis. Liver biopsy and histopathology showed sinusoidal dilatation with non-caseating granulomas. Follow-up fluorodeoxyglucose positron-emission tomography CT scan demonstrated increase in size of the lesion with metabolic activity suspicious of metastasis. The patient underwent segmental liver resection and histopathology showed non-necrotising granuloma with no evidence of malignancy. It is crucial to consider potential side effects of chemotherapeutic agents and have an unbiased approach when evaluating new liver lesions during post treatment follow-up of colorectal cancer. A multidisciplinary tumour board approach comprising of gastroenterologists, medical oncologists, pathologists, radiologists and surgeons is suggested in the management of such patients. The patient is currently doing well and on regular follow-up.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Granuloma/induzido quimicamente , Neoplasias Retais/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Capecitabina/administração & dosagem , Diagnóstico Diferencial , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos
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