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1.
ESMO Open ; 5(5)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33097653

RESUMO

BACKGROUND: Life-threatening diseases have a negative impact on emotional well-being and psychosocial functioning. This study aimed to assess the relationship between the level of anxiety caused by a neoplasm and the threat of coronavirus infection among patients with cancer actively treated with systemic therapy during the COVID-19 pandemic. Additionally, we searched for clinical factors associated with a higher level of anxiety. METHODS: In this multicentre, prospective, non-interventional study conducted in Poland, we enrolled 306 actively treated patients with cancer and collected their clinical data, including age, gender, cancer type and treatment intention. The fear/anxiety of SARS-CoV-2 were rated in Fear of COVID-19 Scale (SRA-FCV-19S) and Numerical Anxiety Scale (SRA-NAS). The fear and anxiety associated with cancer (CRA) were rated with the NAS (CRA-NAS). RESULTS: The mean level of SRA-FCV-19S was 18.5±7.44, which was correlated with the SRA-NAS (r=0.741, p<0.001). SRA-FCV-19S was significantly higher in women versus men (20.18±7.56 vs 16.54±6.83; p<0.001) and was tumour type-dependent (p=0.037), with the highest anxiety observed in patients with breast cancer (17.63±8.75). In the multivariate analysis, only the female gender was significantly associated with higher SRA. CRA-NAS was higher in women versus men (7.07±2.99 vs 5.47±3.01; p<0.001), in patients treated with curative versus palliative intention (7.14±3.06 vs 5.99±3.06; p=0.01) and in individuals aged ≤65 years versus >65 years (6.73±2.96 vs 5.66±3.24; p=0.007). CONCLUSIONS: For an actively treated patient with cancer, cancer remains the main life-threatening disease during the COVID-19 pandemic. The need for more attentive psychological care should be provided especially to female patients, patients with breast cancer, those under 65 years of age and treated with curative intention, as these factors are associated with a higher level of anxiety.


Assuntos
Ansiedade/psicologia , Betacoronavirus , Neoplasias da Mama/psicologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Medo/psicologia , Neoplasias Gastrointestinais/psicologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/virologia , Polônia/epidemiologia , Estudos Prospectivos , Fatores Sexuais
2.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(9): 840-844, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32927506

RESUMO

In patients with recurrent or metastatic gastrointestinal stromal tumor (GIST), imatinib is the mainstay treatment, which has significantly improved outcome. However, approximately half of patients who have initial respose to imatinib will develop secondary resistance within 2 years, leading to progressive disease. Available data suggest that cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib and have relatively low tumor burden, particularly in whom a R0/R1 resection is anticipated. The evidence of benefit from surgery in patients with focal tumor progression on imatinib is limited, but after surgical resection of progressive lesions, shifting to second line therapy should be initiated. Patients with multifocal progression are not suitable for surgical intervention. In the meantime, surgery for patients treated with sunitinib is feasible, yet survival benefit remains controversial. Thus, surgery should be considered in patients with metastatic GIST whose disease responds to imatinib with a goal of performing R0/R1 resection. On a case-by-case basis, surgical intervention should be determined after careful multidisciplinary consultation to achieve safety, improvement of symptoms and long-term survival benefits.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/cirurgia , Procedimentos Cirúrgicos de Citorredução , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/secundário , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Equipe de Assistência ao Paciente , Sunitinibe/uso terapêutico , Resultado do Tratamento , Carga Tumoral
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(9): 917-921, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32927519

RESUMO

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the gastrointestinal tract. Surgical resection is the only curative treatment, while imatinib is the first-line therapy for recurrent, metastatic, and unresectable GIST. However, more than half of GIST patients suffer from secondary resistance to imatinib within 2 years after treatment initiation. Therefore, early diagnosis, drug resistance and recurrence surveillance are critical for GIST patients. Liquid biopsy is a new method which utilizes the detection of tumor biomarkers in peripheral blood for early diagnosis and therapeutic efficacy assessment. In recent years, liquid biopsy has achieved significant research progress in several kinds of malignancy. This review aims at presenting an overview on research advance of liquid biopsy in GIST and may provide a new method for early diagnosis and therapeutic efficacy assessment of GIST.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Biópsia Líquida , Recidiva Local de Neoplasia/diagnóstico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/sangue , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/etiologia
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 1011-1016, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32933636

RESUMO

To study the clinical effect of oral sirolimus in the treatment of children with blue rubber bleb nevus syndrome (BRBNS) in the gastrointestinal tract, a retrospective analysis was performed on the clinical data and follow-up results of two children with BRBNS treated by sirolimus. The two children with BRBNS had gastrointestinal bleeding and anemia and were treated with sirolimus at a dose of 1 mg/day as part of treatment. The plasma concentration of the drug was maintained between 2.5-12.0 ng/mL. The children showed disappearance of gastrointestinal bleeding and improvements in anemia and coagulation function, and blood transfusion could be stopped during treatment, with no obvious adverse drug reactions. PubMed, Wanfang Data, and CNKI were searched for related articles on sirolimus in the treatment of BRBNS. A total of 26 cases of children with BRBNS, aged 0-18 years, were obtained. With the addition of the 2 cases in this study, sirolimus treatment achieved a satisfactory clinical effect in all 28 cases. Sirolimus may be effective and safe in the treatment of children with BRBNS, and further prospective studies are needed to evaluate the long-term efficacy of this drug.


Assuntos
Neoplasias Gastrointestinais , Nevo Azul , Sirolimo/uso terapêutico , Neoplasias Cutâneas , Adolescente , Criança , Pré-Escolar , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Nevo Azul/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico
5.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815695

RESUMO

Pemphigus is an autoimmune bullous disease with a number of described associations, including medications, which have been grouped into three structural categories - thiol drugs, phenol drugs, and drugs with neither functional group [1]. Discontinuation of the offending medication is considered a mainstay of therapy. We report a patient in whom the onset of pemphigus foliaceus was associated with initiation of imatinib mesylate adjuvant therapy in a patient with resected gastrointestinal stromal tumor (GIST). Imatinib was continued because of the survival benefit to the patient with a resected, high risk GIST. Treatment with rituximab resulted in near resolution of his blistering rash and follow up enzyme-linked immunosorbent assay (ELISA) demonstrated reference range immunoreactivity for both desmoglein 1 and desmoglein 3. After dose increase of imatinib therapy owing to tumor growth, the patient subsequently again developed a similar eruption. Re-biopsy and ELISA were consistent with recurrence of pemphigus. In conclusion, although the patient's pemphigus was cleared with a single cycle of rituximab infusions while continuing imatinib therapy, the disease returned after imatinib dose was increased a year later, suggesting a dose-response relationship.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/efeitos adversos , Fatores Imunológicos/uso terapêutico , Pênfigo/induzido quimicamente , Rituximab/uso terapêutico , Pele/patologia , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Biópsia , Relação Dose-Resposta a Droga , Neoplasias Gastrointestinais/complicações , Tumores do Estroma Gastrointestinal/complicações , Humanos , Mesilato de Imatinib/administração & dosagem , Masculino , Pênfigo/tratamento farmacológico , Pênfigo/patologia
6.
Lancet Oncol ; 21(7): 935-946, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32615108

RESUMO

BACKGROUND: Targeting of KIT and PDGFRA with imatinib revolutionised treatment in gastrointestinal stromal tumour; however, PDGFRA Asp842Val (D842V)-mutated gastrointestinal stromal tumour is highly resistant to tyrosine kinase inhibitors. We aimed to assess the safety, tolerability, and antitumour activity of avapritinib, a novel KIT and PDGFRA inhibitor that potently inhibits PDGFRA D842V, in patients with advanced gastrointestinal stromal tumours, including patients with KIT and PDGFRA D842V-mutant gastrointestinal stromal tumours (NAVIGATOR). METHODS: NAVIGATOR is a two-part, open-label, dose-escalation and dose-expansion, phase 1 study done at 17 sites across nine countries (Belgium, France, Germany, Poland, Netherlands, South Korea, Spain, the UK, and the USA). Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 2 or less, and with adequate end-organ function were eligible to participate. The dose-escalation part of the study included patients with unresectable gastrointestinal stromal tumours. The dose-expansion part of the study included patients with an unresectable PDGFRA D842V-mutant gastrointestinal stromal tumour regardless of previous therapy or gastrointestinal stromal tumour with other mutations that either progressed on imatinib and one or more tyrosine kinase inhibitor, or only received imatinib previously. On the basis of enrolment trends, ongoing review of study data, and evolving knowledge regarding the gastrointestinal stromal tumour treatment paradigm, it was decided by the sponsor's medical director together with the investigators that patients with PDGFRA D842V mutations would be analysed separately; the results from this group of patients is reported in this Article. Oral avapritinib was administered once daily in the dose-escalation part (starting dose of 30 mg, with increasing dose levels once daily in continuous 28-day cycles until the maximum tolerated dose or recommended phase 2 dose was determined; in the dose-expansion part, the starting dose was the maximum tolerated dose from the dose-escalation part). Primary endpoints were maximum tolerated dose, recommended phase 2 dose, and safety in the dose-escalation part, and overall response and safety in the dose-expansion part. Safety was assessed in all patients from the dose-escalation part and all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour in the dose-expansion part, and activity was assessed in all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour who received avapritinib and who had at least one target lesion and at least one post-baseline disease assessment by central radiology. This study is registered with ClinicalTrials.gov, NCT02508532. FINDINGS: Between Oct 26, 2015, and Nov 16, 2018 (data cutoff), 46 patients were enrolled in the dose-escalation part, including 20 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour, and 36 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour were enrolled in the dose-expansion part. At data cutoff (Nov 16, 2018), 38 (46%) of 82 patients in the safety population (median follow-up of 19·1 months [IQR 9·2-25·5]) and 37 (66%) of the 56 patients in the PDGFRA D842V population (median follow-up of 15·9 months [IQR 9·2-24·9]) remained on treatment. The maximum tolerated dose was 400 mg, and the recommended phase 2 dose was 300 mg. In the safety population (patients with PDGFRA D842V-mutant gastrointestinal stromal tumour from the dose-escalation and dose-expansion parts, all doses), treatment-related grade 3-4 events occurred in 47 (57%) of 82 patients, the most common being anaemia (14 [17%]); there were no treatment-related deaths. In the PDGFRA D842V-mutant population, 49 (88%; 95% CI 76-95) of 56 patients had an overall response, with five (9%) complete responses and 44 (79%) partial responses. No dose-limiting toxicities were observed at doses of 30-400 mg per day. At 600 mg, two patients had dose-limiting toxicities (grade 2 hypertension, dermatitis acneiform, and memory impairment in patient 1, and grade 2 hyperbilirubinaemia in patient 2). INTERPRETATION: Avapritinib has a manageable safety profile and has preliminary antitumour activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumours. FUNDING: Blueprint Medicines.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mutação , Pirazóis/uso terapêutico , Pirróis/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Triazinas/uso terapêutico , Idoso , Feminino , Seguimentos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Lancet Oncol ; 21(7): 923-934, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32511981

RESUMO

BACKGROUND: Resistance to approved inhibitors of KIT proto-oncogene, receptor tyrosine kinase (KIT), and platelet-derived growth factor receptor α (PDGFRA) is a clinical challenge for patients with advanced gastrointestinal stromal tumours. We compared the efficacy and safety of ripretinib, a switch-control tyrosine kinase inhibitor active against a broad spectrum of KIT and PDGFRA mutations, with placebo in patients with previously treated, advanced gastrointestinal stromal tumours. METHODS: In this double-blind, randomised, placebo-controlled, phase 3 study, we enrolled adult patients in 29 specialised hospitals in 12 countries. We included patients aged 18 years or older who had advanced gastrointestinal stromal tumours with progression on at least imatinib, sunitinib, and regorafenib or documented intolerance to any of these treatments despite dose modifications, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Eligible patients were randomly assigned (2:1) to receive either oral ripretinib 150 mg once daily (ripretenib group) or placebo once daily (placebo group). Randomisation was done via an interactive response system using randomly permuted block sizes of six and stratified according to number of previous therapies and ECOG performance status. Patients, investigators, research staff, and the sponsor study team were masked to a patient's treatment allocation until the blinded independent central review (BICR) showed progressive disease for the patient. The primary endpoint was progression-free survival, assessed by BICR. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who received at least one dose of study drug. Patients randomly assigned to placebo were permitted to cross over to ripretinib 150 mg at the time of disease progression. The INVICTUS study is registered with ClinicalTrials.gov, number NCT03353753, and with WHO International Clinical Trials Registry Platform, number EUCTR2017-002446-76-ES; follow-up is ongoing. FINDINGS: Between Feb 27, 2018, and Nov 16, 2018, 129 of 154 assessed patients were randomly assigned to receive either ripretinib (n=85) or placebo (n=44). At data cutoff (May 31, 2019), at a median follow-up of 6·3 months (IQR 3·2-8·2) in the ripretinib group and 1·6 months (1·1-2·7) in the placebo group, 51 patients in the ripretinib group and 37 in the placebo group had had progression-free survival events. In the double-blind period, median progression-free survival was 6·3 months (95% CI 4·6-6·9) with ripretinib compared with 1·0 months (0·9-1·7) with placebo (hazard ratio 0·15, 95% CI 0·09-0·25; p<0·0001). The most common (>2%) grade 3 or 4 treatment-related treatment-emergent adverse events in the ripretinib group (n=85) included lipase increase (four [5%]), hypertension (three [4%]), fatigue (two [2%]), and hypophosphataemia (two (2%]); in the placebo group (n=43), the most common (>2%) grade 3 or 4 treatment-related treatment-emergent adverse events were anaemia (three [7%]), fatigue (one [2%]), diarrhoea (one [2%]), decreased appetite (one [2%]), dehydration (one [2%]), hyperkalaemia (one [2%]), acute kidney injury (one [2%]), and pulmonary oedema (one [2%]). Treatment-related serious adverse events were reported in eight (9%) of 85 patients who received ripretinib and three (7%) of 43 patients who received placebo. Treatment-related deaths occurred in one patient in the placebo group (septic shock and pulmonary oedema) and one patient in the ripretinib group (cause of death unknown; the patient died during sleep). INTERPRETATION: Ripretinib significantly improved median progression-free survival compared with placebo and had an acceptable safety profile in patients with advanced gastrointestinal stromal tumours who were resistant to approved treatments. FUNDING: Deciphera Pharmaceuticals.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Seguimentos , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
9.
Eur J Cancer ; 134: 62-74, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32470848

RESUMO

BACKGROUND: Gastrointestinal stromal tumour (GIST) is commonly treated with tyrosine kinase inhibitors (TKIs), but most patients ultimately develop secondary resistance. Cabozantinib, a multi-targeted TKI inhibitor, has activity in patient-derived GIST mouse xenograft models and can overcome compensatory MET signalling occurring on TKI treatment. European Organisation for Treatment of Cancer (EORTC) 1317 'CaboGIST' assessed the safety and activity of cabozantinib in patients with GIST who had progressed on imatinib and sunitinib. METHODS: In this multi-center, open label, single arm phase II study, eligible GIST patients received oral cabozantinib (60 mg) once daily. Primary end-point was the progression-free survival rate at 12 weeks assessed by the local investigator per Response Evaluation Criteria in Solid Tumours 1·1. If at least 21 of the first 41 eligible and evaluable patients were progression-free at week 12, the activity of cabozantinib was sufficient to warrant further exploration according to the A'Hern one-stage study design. FINDINGS: A total of 50 eligible patients started treatment between 02/2017 and 08/2018, including four (8%) still continuing cabozantinib at clinical cut-off (09/2019). The number of 3-weekly treatment cycles ranged from 1 to 30. Among the first 41 eligible and evaluable patients, 24 were progression-free at week 12 (58·5%, 95% confidence interval [CI] 42·0-74·0%). Among all 50 patients, 30 were progression-free at week 12 (60%, 95% CI 45-74%). Seven patients achieved a partial response (14%, 95% CI 6-27%), and 34 had stable disease (68%, 95% CI 53-80%) as best response. Progression was seen in eight patients (16%, 95% CI 7-29%), and one was not evaluable. Disease control was achieved in 41 patients (82%, 95% CI 69-91%). Median progression-free survival was 5·5 months (95% CI 3·6-6·9). The most common adverse events were diarrhoea (76%), palmar-plantar erythrodysesthesia syndrome (60%), fatigue (50%), hypertension (42%), weight loss (40%) and oral mucositis (30%), with 32 (64%) patients requiring dose reductions, 27 (54%) having treatment interruptions and no cabozantinib-related deaths observed. INTERPRETATION: EORTC 1317 met its primary end-point, with 24/41 patients being progression-free at week 12 of treatment. The objective response was 14% with an encouraging disease control rate of 82%. Results of this trial confirm preclinical findings and warrant further exploration of cabozantinib in GIST. CLINICAL TRIAL NUMBERS: EORTC 1317, NCT02216578, EudraCT 2014-000501-13.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/administração & dosagem , Feminino , Seguimentos , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/secundário , Humanos , Mesilato de Imatinib/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Piridinas/administração & dosagem , Sunitinibe/administração & dosagem , Taxa de Sobrevida
10.
Am Surg ; 86(4): 284-292, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32391751

RESUMO

Progress in the arena of cancer immunotherapy has been immense in recent years. The fact remains that most of the cancer resections in the United States are performed by general surgeons and not oncologic specialists. A busy practice in general surgery will invariably make it difficult to keep pace with such rapid advancement. This review offers a concise summary of the major concepts and trials that have driven the immunotherapy revolution and their implications for surgeons who deliver cancer care.


Assuntos
Imunoterapia , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Imunoterapia/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Receptor de Morte Celular Programada 1/imunologia
12.
Am J Clin Oncol ; 43(5): 305-310, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32343515

RESUMO

OBJECTIVES: Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC. METHODS: This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m, oxaliplatin 80 mg/m on day 1, CP 1000 mg/m twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate. RESULTS: Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed. CONCLUSIONS: First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Adulto , Idoso , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Carcinoma Neuroendócrino/mortalidade , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
13.
Oncology ; 98(7): 445-451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348984

RESUMO

BACKGROUND: Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. METHODS: A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with latest-generation TKI (nilotinib, dasatinib, and ponatinib), while group B included patients treated with first-generation TKI (imatinib). Cardiological evaluation included electrocardiogram, echocardiogram with global longitudinal strain of left ventricle (GLS), and carotid ultrasound scan with arterial stiffness measurement (pulse wave velocity, PWV). Adverse cardiovascular events were recorded in both groups. RESULTS: Statistical analysis showed that cardiovascular adverse events (myocardial ischemia, peripheral artery disease, deep vein thrombosis, and pleural effusion) were significantly more frequent in group A than group B (p value = 0.044). Moreover, there was a significant reduction in GLS and PWV in group A when compared to group B (respectively, p = 0.03 and p = 0.004). CONCLUSIONS: Our study confirms that imatinib is a relatively safe drug, while it reveals that the latest-generation TKIs may cause a burden of cardiovascular complications. GLS and PWV allow detection of early signs of cardiac and vascular toxicity in oncohematologic patients treated with TKI, and their use is advisable.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Doença da Artéria Coronariana/induzido quimicamente , Dasatinibe/efeitos adversos , Dasatinibe/uso terapêutico , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Piridazinas/efeitos adversos , Piridazinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
14.
J Cancer Res Clin Oncol ; 146(8): 2089-2097, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32227265

RESUMO

OBJECTIVE: To evaluate the patterns of vitamin and herbal supplement use among patients with advanced gastrointestinal (GI) cancers and the association of such behavior with the efficacy and toxicity of systemic anticancer treatment. METHODS: Project data sphere (PDS) was used to access de-identified datasets of eight clinical trials of advanced GI cancers. Multivariable logistic regression analysis was used to identify factors predicting the use of supplements. Kaplan-Meier survival estimates were used to evaluate the association of supplement use with overall and progression-free survival. Results were stratified according to the site of the primary tumor [pancreatic, gastric, colorectal or hepatocellular carcinoma (HCC)] The association between supplement use and selected chemotherapy side effects was evaluated through Chi-squared testing and subsequent logistic regression. RESULTS: A total of 3441 patients were included in the analysis. Of these, 775 patients reported use of supplements and 2666 patients reported no use of supplements. Higher ECOG performance score (Odds ratio: OR for ECOG 1 versus 0: 1.629; 95% CI 1.363-1.947; P < 0.001) and pancreatic primary site (OR for gastric cancer versus pancreatic cancer: 0.538; 95% CI 0.408-0.709; P < 0.001) was associated with greater use of these supplements. Supplement use was associated with a better overall survival among patients with pancreatic cancer (P = 0.002) but not other GI malignancies. Supplement use was associated with a higher probability of anemia and diarrhea among patients with pancreatic cancer (P < 0.001 for both), gastric cancer (P = 0.016; P = 0.036, respectively) and colorectal cancer (P < 0.001 for both). CONCLUSIONS: There is an association between the use of vitamin and herbal supplements and a higher probability of hematologic and gastrointestinal toxicities. There is a need for more studies to confirm the association between such behavior and better overall survival among patients with pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Gastrointestinais/dietoterapia , Neoplasias Gastrointestinais/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Vitaminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Vitaminas/efeitos adversos
15.
Cancer Chemother Pharmacol ; 85(4): 711-722, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32152679

RESUMO

PURPOSE: To describe 5-fluorouracil (5FU) pharmacokinetics, myelotoxicity and respective covariates using a simultaneous nonlinear mixed effect modelling approach. METHODS: Thirty patients with gastrointestinal cancer received 5FU 650 or 1000 mg/m2/day as 5-day continuous venous infusion (14 of whom also received cisplatin 20 mg/m2/day). 5FU and 5-fluoro-5,6-dihydrouracil (5FUH2) plasma concentrations were described by a pharmacokinetic model using NONMEM. Absolute leukocyte counts were described by a semi-mechanistic myelosuppression model. Covariate relationships were evaluated to explain the possible sources of variability in 5FU pharmacokinetics and pharmacodynamics. RESULTS: Total clearance of 5FU correlated with body surface area (BSA). Population estimate for total clearance was 249 L/h. Clearances of 5FU and 5FUH2 fractionally changed by 77%/m2 difference from the median BSA. 5FU central and peripheral volumes of distribution were 5.56 L and 28.5 L, respectively. Estimated 5FUH2 clearance and volume of distribution were 121 L/h and 96.7 L, respectively. Baseline leukocyte count of 6.86 × 109/L, as well as mean leukocyte transit time of 281 h accounting for time delay between proliferating and circulating cells, was estimated. The relationship between 5FU plasma concentrations and absolute leukocyte count was found to be linear. A higher degree of myelosuppression was attributed to combination therapy (slope = 2.82 L/mg) with cisplatin as compared to 5FU monotherapy (slope = 1.17 L/mg). CONCLUSIONS: BSA should be taken into account for predicting 5FU exposure. Myelosuppression was influenced by 5FU exposure and concomitant administration of cisplatin.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Neoplasias Gastrointestinais/tratamento farmacológico , Modelos Biológicos , Células Mieloides/patologia , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Seguimentos , Neoplasias Gastrointestinais/patologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Células Mieloides/efeitos dos fármacos , Dinâmica não Linear , Prognóstico , Distribuição Tecidual
16.
BMC Complement Med Ther ; 20(1): 15, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32020863

RESUMO

BACKGROUND: Gastrointestinal cancer is one of the most common malignancies and imposes heavy burdens on both individual health and social economy. We sought to survey the effect of a self-care education program on quality of life and fatigue in gastrointestinal cancer patients who received chemotherapy. METHODS: Ninety-one eligible gastrointestinal cancer patients were enrolled in this study and 86 valid samples were analyzed. Data were acquired with a demographics questionnaire, endpoint multidimensional questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30. The collected data were analyzed using SPSS software. RESULTS: The self-care education intervention significantly improved the quality of life with respect to emotional function (p = 0.018), role function (p = 0.041), cognitive function (p = 0.038) and alleviated side effects such as nausea/vomiting (p = 0.028) and fatigue (p = 0.029). Further analysis demonstrated that the self-care education benefited total fatigue, affective fatigue and cognitive fatigue in gastrointestinal cancer patients regardless of baseline depression. CONCLUSION: Our results suggested the beneficial effects of the self-care education in both quality of life and anti-fatigue in gastrointestinal cancer patients under chemotherapy. The self-care education could be considered as a complementary approach during combination chemotherapy in gastrointestinal cancer patients.


Assuntos
Fadiga/terapia , Neoplasias Gastrointestinais/tratamento farmacológico , Educação de Pacientes como Assunto/métodos , Qualidade de Vida , Autocuidado , Adulto , Idoso , Fadiga/etiologia , Feminino , Neoplasias Gastrointestinais/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
17.
J Oncol Pharm Pract ; 26(6): 1511-1515, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32067560

RESUMO

CASE REPORT: Imatinib mesylate is a well-known tyrosine kinase inhibitor used to treat chronic myeloid leukemia, gastrointestinal stromal tumor, as well as a variety of other malignancies.Management and outcome: As use of this medication continues to grow, providers must be aware of potential side effects and management thereof. The toxicity profile of imatinib has been well characterized with most patients experiencing a grade 1 or 2 adverse event. These side effects are usually mild, and most patients can continue treatment without interruption. Around 30% of patients on imatinib experience skin toxicity, with 5% being high grade. This rash is typically hypopigmented, which is explained by imatinib's effect on melanocytes. DISCUSSION: Although there have been several case reports describing hyperpigmentation of the oral mucosa or nails, very few have described skin hyperpigmentation. We previously reported the first two cases of imatinib-related squamous cell carcinoma in patients undergoing treatment for gastrointestinal stromal tumors. In this paper, we present a case of a patient on imatinib for management of gastrointestinal stromal tumor who experienced extensive skin hyperpigmentation and review the literature.


Assuntos
Antineoplásicos/efeitos adversos , Hiperpigmentação/induzido quimicamente , Mesilato de Imatinib/efeitos adversos , Idoso , Antineoplásicos/administração & dosagem , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico
18.
Cancer Immunol Immunother ; 69(6): 969-982, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32078695

RESUMO

Esophageal and gastric cancers collectively cause over 1.1 million deaths annually and only 20-30% of patients respond favorably to current therapies. Cellular therapies using invariant natural killer T (iNKT) cells are showing promise for patients with other cancers; therefore, we investigated if these cells are altered in esophageal and gastric cancer patients. Flow cytometric analysis of peripheral blood from 139 patients revealed that iNKT cells are depleted from patients with esophageal and gastric adenocarcinoma and esophageal squamous cell carcinoma, both before and after treatment. Interrogation of the KMPlot database of transcriptomic data from 876 gastric cancer patients revealed that low CD1d expression is associated with poor prognosis. These observations suggest that therapies that boost CD1d expression and iNKT cell responses may benefit these patients. However, we found that chemotherapies used for esophageal and gastric cancers have adverse effects on iNKT cells in vitro. Cisplatin caused a significant reduction of CD1d expression by esophageal tumor cell lines. Cisplatin, 5-fluorouracil and carboplatin induced dose-dependent apoptosis in primary lines of iNKT cells and inhibited CD1d-dependent interferon-γ production and cytolytic degranulation by viable iNKT cells. Interestingly, cisplatin increased granzyme B and perforin production and decreased the production of the granzyme B inhibitor PI9, which protects cytotoxic cells from self-damage by granzyme B. Thus, cisplatin-induced apoptosis of iNKT cells may be mediated in part by altering granzyme B and PI9 expression. Our data suggest that iNKT cell-based immunotherapies may benefit patients with gastrointestinal cancers, but may be negatively affected by chemotherapies used for these cancers.


Assuntos
Antígenos CD1d/metabolismo , Neoplasias Gastrointestinais/genética , Células T Matadoras Naturais/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/imunologia , Humanos , Pessoa de Meia-Idade
19.
Anticancer Res ; 40(2): 865-871, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32014930

RESUMO

BACKGROUND/AIM: Oxaliplatin-induced neurotoxicity (OIN) can be severe and dose-limiting with clinically significant symptoms that persist for years. Few published reports have described postoperative exacerbation of OIN and more longitudinal data are needed to better characterize the phenomenon. PATIENTS AND METHODS: We identified 13 patients diagnosed with colon (n=7), rectal (n=4) or pancreatic (n=2) cancer who experienced postoperative OIN exacerbation at our medical center. Charts were reviewed for demographic and clinical data regarding OIN. RESULTS: OIN exacerbation was documented 0.5-7.0 months after the first surgery following oxaliplatin exposure, with a median duration of 10.6 months (range=1.4-86.1 months). OIN exacerbation persisted in 3/13 patients at last follow-up, and improved to pre-operative levels in 6/13 patients (with complete resolution in 4/13) within a median of 3.6 months from initial exacerbation. CONCLUSION: Given the widespread use of oxaliplatin in neoadjuvant and first-line treatment for gastrointestinal cancers, further study is warranted to prospectively and systematically define risks for postoperative OIN exacerbation.


Assuntos
Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Oxaliplatina/uso terapêutico , Adulto , Feminino , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/farmacologia , Período Pós-Operatório
20.
Bull Cancer ; 107(4): 447-457, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32067719

RESUMO

The advent of molecular biology resulted in the discovery of new oncogenes that have led to the development of targeted therapies for the management of cancer patients. The development of these therapies has improved the prognosis of patients in various tumour localizations. The TRK receptor (tropomyosin receptor kinase) is a transmembrane receptor with a tyrosine kinase activity that plays a role in both cell proliferation and the physiology of the nervous system. Fusions involving the NTRK gene, which codes for this receptor, have been found in different types of solid tumours and lead to its constitutional activation. These fusions, however uncommon, are mainly found in rare pediatric tumours but can also be encountered in digestive cancers with high prevalence (such as colorectal cancer, especially in case of microsatellite instability, with a frequency of 2.5 to 38.5 %) or in aggressive cancers (such as pancreatic cancer). Therapies targeting TRK, such as larotrectinib or entrectinib, have shown significant response rates, usually greater than 6 months, for tumours from various primary sites presenting NTRK fusions and refractory to standard therapies. These fusions can be detected by different methods: immunohistochemistry, FISH (fluorescence in situ hybridization) as well as NGS (next generation sequencing). The intent of this review is to report on current knowledge on NTRK fusions in oncology and to discuss the role of these fusions in digestive cancers and potential therapeutic implications.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Fusão Gênica , Fatores de Crescimento Neural/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Oncogênicas/genética , Benzamidas/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização In Situ , Indazóis/uso terapêutico , Glicoproteínas de Membrana/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Receptor trkA/genética , Receptor trkB/genética , Receptor trkC/genética
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