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1.
Medicine (Baltimore) ; 99(7): e19258, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049866

RESUMO

Primary tumor resection (PTR) for unresectable metastatic colorectal cancer (mCRC) patients has been documented to be associated with postoperative hyper-neovascularization and enhanced growth of metastases, which may be prevented by bevacizumab. This study aimed to investigate the survival outcome of PTR in patients who received palliative bevacizumab-containing chemotherapy (BCT).From January 2006 to December 2018, medical records of 240 mCRC patients who received palliative BCT at a single tertiary colorectal cancer center were retrospectively reviewed. Patients were classified into three groups: PTR-a (PTR before BCT, n = 60), PTR-b (PTR during BCT, n = 17), and BCT-only group (n = 163). Resectable mCRCs or recurrent diseases were excluded, and the end-point was overall survival (OS) rate.Three groups had similar age, cell differentiation, location of the primary tumor, and the number of metastatic organs. More than two-thirds of patients who received PTR experienced disease-progressions (PD) during their postoperative chemotherapy-free time (PTR-a vs PTR-b; 66.7% vs 76.5%, P = .170), but OS was not inferior to the BCT-only group (PTR-a vs BCT-only; HR 0.477 [95% CI 0.302-0.754], P = .002/PTR-b vs BCT-only; HR 0.77 [95% CI 0.406-1.462], P = .425). The postoperative chemotherapy-free time was similar between PTR-a and PTR-b (median 32.0 [14-98] days vs 41.0 [18-71] days, P = .142), but non-obstructive indications (perforation, bleeding, pain) were the more frequent in the PTR-b than PTR-a. Young age, the number of BCT, and PTR-a were the independent factors for OS.The efficacy of the PTR for unresectable mCRC has been controversial, but this study demonstrated that PTR should be considered for the unresectable mCRC patients regardless before and during BCT.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Cuidados Paliativos , República da Coreia/epidemiologia , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 99(5): e19077, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000459

RESUMO

Retinal arterial macroaneurysms (RAMs) develop as outpouchings of the arterial wall that is weakened by arteriosclerosis. The traditional treatment of RAMs comprises observation, focal laser photocoagulation, or surgery. Recently, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has been announced as an effective therapy for fovea-threatening RAMs and quickly improve visual acuity and central retinal thickness (CRT).In the retrospective series, medical charts and ocular images of 24 patients diagnosed as having RAM between May 2011 and November 2018 in our facility were reviewed to delineate clinical manifestations and visual prognosis in RAM patients receiving different treatment modalities. Twenty-four patients (25 eyes; 11 men and 13 women) were enrolled, and one eye with comorbidity of branch retinal vein occlusion was excluded. The mean age of the patients was 69.00 ±â€Š13.45 years. Fourteen patients (58.33%) had a history of hypertension, and 17 patients (70.83%) were aged > 60 years. Furthermore, patients with fovea-threatening RAMs presented with either hypertension or were aged > 60 years.Eyes with fovea involvement (n = 18) were analyzed and separated into two groups according to their treatment modalities: those receiving anti-VEGF intravitreal injections (n = 13) and observation only (n = 5). The baseline visual acuity revealed no significant difference in the two groups. In patients receiving anti-VEGF intravitreal injections, a significantly better visual acuity was detected after anti-VEGF intravitreal injections than the baseline visual acuity (logMAR, 0.78 ±â€Š0.51 vs 1.52 ±â€Š0.48, P < .001), and CRT significantly improved (505.50 ±â€Š159.26 µm vs 243.60 ±â€Š60.17 µm, P = .001). Patients receiving anti-VEGF intravitreal injections also revealed better final visual acuity than those in the observation group (logMAR, 0.78 ±â€Š0.51 vs 1.34 ±â€Š0.48, P = .04).A systematic work-up for hypertension and arteriosclerotic disease could be considered the recommended procedure once RAM has been diagnosed. With better final visual acuity, significant visual improvements, and fast reduction of CRT observed in patients with fovea-threatening RAMs receiving anti-VEGF intravitreal injections, intravitreal anti-VEGF was considered an effective therapy for complicated RAM. During the follow-up period, the majority of RAM eyes had good maintenance of visual function even with foveal complications.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Tomada de Decisões , /tratamento farmacológico , Idoso , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Acuidade Visual
3.
Medicine (Baltimore) ; 99(3): e18771, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011468

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis despite conventional treatments of surgery, radiotherapy, and chemotherapy. Small-molecule tyrosine kinase inhibitors acting on epidermal growth factor receptor (EGFR) have shown high efficacy and low toxicity for NSCLC. In particular, combining erlotinib with the VEGF antibody bevacizumab has therapeutic value in NSCLC, but the drugs' separate effects as monotherapy and any adverse outcomes of combination therapy remain unclear. OBJECTIVES: To determine the efficacy and safety of erlotinib and bevacizumab for NSCLC, we conducted a meta-analysis and systematic review of randomized controlled trials. DATA SOURCES: PubMed, Embase, Web of Science, and Cochrane databases were searched using keywords and manual review. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We reviewed randomized controlled trials on the use of erlotinib combined with bevacizumab in adult patients with NSCLC, including data on outcome measures of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events. STUDY APPRAISAL AND SYNTHESIS METHODS: After quality assessment, datasets were evaluated for heterogeneity. In the event of significant heterogeneity, a random-effects model was used to assess the overall outcome measures as a result of treatments. Subgroup analysis was conducted to evaluate the source of heterogeneity on PFS. RESULTS: Compared with erlotinib or bevacizumab alone, the combined treatment did not significantly prolong OS (95% confidence interval [CI] = 0.84-1.11; P = .62) or increase the ORR (95% CI = 0.91-1.20; P = .52), but significantly improved PFS (95% CI = 0.58-0.73; P < .001). This improvement was especially notable in patients with the following characteristics: Eastern Cooperative Oncology Group Performance Status score of 0 or 1, female, no smoking history, adenocarcinoma, and EGFR Exon19 deletion or Exon21 Leu858Arg mutation. Combination therapy significantly increased incidence of grade 1-2 hypertension (20.3% vs 6.3%, 95% CI 1.73-5.88; P < .01) and severe diarrhea (10% vs 3.2%, 95% CI 1.36-6.60; P = .01). LIMITATIONS: The low number of available randomized controlled trials could influence interpretation. CONCLUSIONS: Compared with erlotinib or bevacizumab monotherapy, their combination effectively prolongs PFS but increases incidence of adverse events in NSCLC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Medicine (Baltimore) ; 99(8): e19226, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080119

RESUMO

Treatment options for recurrent glioblastoma are rare, with their response uncertain. This study aimed to determine the response of chemotherapy including bevacizumab in combination with vincristine and carboplatin for glioblastoma at first recurrence in a single-institution cohort.Clinical data of patients who received chemotherapy including bevacizumab, vincristine, and low-dose carboplatin for recurrent glioblastoma between 2008 and 2014 were analyzed. Differences between those who received combination chemotherapy (chemotherapy-positive) and those who did not (chemotherapy-negative) were estimated by Fisher exact test or Wilcoxon rank-sum test, as appropriate. Survival curves were estimated using the Kaplan-Meier method, and differences between survival curves were estimated by the log-rank test. Univariate analysis of treatment response for all recurrent glioblastoma patients and secondary recurrence patients under different conditions were evaluated using Wilcoxon rank-sum test or the Kruskal-Wallis test.Although mortality rates were similar between the chemotherapy-negative and chemotherapy-positive groups (26.7% vs 28.6%), median overall survival was significantly longer in the chemotherapy-positive group than the chemotherapy-negative group (P = .006). There were no chemotherapy-related serious complications such as gastrointestinal perforation, serious bleeding, or new-onset seizure during chemotherapy, whereas others side effects including proteinuria and hypertension were more common albeit well controlled by medication.This study revealed combination regimen of bevacizumab, vincristine, and low-dose carboplatin as a potentially effective therapeutic approach in recurrent glioblastoma. More in-depth understanding of the mechanism underlying this combination treatment and potential contribution of alternative genetic therapeutic in recurrent glioblastoma is necessary.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/mortalidade , Carboplatina/uso terapêutico , Feminino , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taiwan , Vincristina/uso terapêutico
8.
BMC Med Genet ; 21(1): 3, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900123

RESUMO

BACKGROUND: Liquid biopsies of blood plasma cell free DNA can be used to monitor treatment response and potentially detect mutations that are present in resistant clones in metastatic cancer patients. CASE PRESENTATION: In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle, CT imaging, CEA and CA19-9 markers validated the cfDNA findings of treatment response. However, 5 weeks later, the tumour had rapidly progressed. CONCLUSION: As FOLFIRI+Bevacizumab has recently also been associated with sustained complete remission in a APC/TP53/KRAS triple-mutated patient, these driver genes should be tested and monitored in a more in-depth manner in future patients. Patients with metastatic disease should be monitored more closely during and after chemotherapy, ideally using cfDNA.


Assuntos
Proteína da Polipose Adenomatosa do Colo/sangue , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/sangue , Proteína Supressora de Tumor p53/sangue , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , 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 , Ácidos Nucleicos Livres/sangue , DNA Tumoral Circulante/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas p21(ras)/genética , Indução de Remissão , Proteína Supressora de Tumor p53/genética
9.
Arch Esp Urol ; 73(1): 68-70, 2020 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31950926

RESUMO

INTRODUCTION: Bevacizumab is a monoclonalantibody used as a targeted therapy in blocking vascularendothelial growth factor in different types of oncologicaland non-oncological diseases. It has demonstratedsurvival benefits in the treatment of many types of malignanttumors, including lung cancer. As all drugs have adverseeffects, one of the most uncommon being gastrointestinalperforation and few cases of ureteral stenosis. However,they do not mention or describe the perforation of segmentsof the urinary tract. OBJECTIVE: To describe renal pelvic perforation as an adverseeffect to the use of Bevacizumab. CASE DESCRIPTION: 67-year-old male patient with metastaticlung cancer being treated with Bevacizumab whohas perforation of the renal pelvis is presented. A pyelogramwas performed showing contrast extravasation at theleft renal pelvis and a double J catheter was placed, witha satisfactory clinical course, and tomographic control at 1month without evidence of extravasation of contrast, withdrawingdouble catheter J. CONCLUSION: Renal pelvic perforation secondary toBevacizumab is infrequent, but it must be taken into accountin patients treated with this drug.


Assuntos
Antineoplásicos Imunológicos , Bevacizumab , Extravasamento de Materiais Terapêuticos e Diagnósticos , Pelve Renal , Neoplasias Pulmonares , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Humanos , Pelve Renal/patologia , Neoplasias Pulmonares/tratamento farmacológico , Masculino
10.
Gynecol Oncol ; 156(1): 13-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708167

RESUMO

BACKGROUND: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. METHODS: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. FINDINGS: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. INTERPRETATION: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). FUNDING: National Cancer Institute.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Epitelial do Ovário/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Peritoneais/patologia , Intervalo Livre de Progressão
11.
Gynecol Oncol ; 156(1): 32-37, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739991

RESUMO

BACKGROUND: Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. METHODS: In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. RESULTS: Fifty patients were enrolled. Median age was 60.5 years (range 28-82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67-42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. CONCLUSIONS: Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão
13.
Int J Cancer ; 146(6): 1643-1651, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31318983

RESUMO

The treatment landscape in metastatic renal cell carcinoma has changed fundamentally over the last decade by the development of antiangiogenic agents, mammalian target of rapamycin inhibitors and immunotherapy. Outside of the context of a clinical trial, the treatments are used sequentially. We describe results under real-life conditions of a sequential treatment strategy, before the era of immunotherapy. All patients were treated according to their prognostic score (either Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium) for advanced renal cell carcinoma. A treatment strategy involving 1 to 4 lines was determined including a rechallenge criterion for the repeat use of a treatment class. Three hundred forty-four patients were included over 3 years. Overall survival was 57 months in patients with good or intermediate prognosis and 19 months in patients with poor prognosis. In the former group, the proportions of patients treated with 2 to 4 treatment lines were 70%, 38% and 16%, respectively. The best objective response rates for lines 1 to 4 were 46%, 36%, 16% and 17%, respectively. Grade III/IV toxicity did not appear to be cumulative. The recommended strategy was followed in 68% of patients. A large proportion of patients with good or intermediate prognosis who progress after two lines of treatment still have a performance status good enough to receive a systemic treatment, which justifies such a strategy. Overall survival of patients with good and intermediate prognosis was long, suggesting a benefit from the applied approach. These results might be used as selection criterion for the treatment of patients in the era of immune checkpoint inhibitors.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/uso terapêutico , Carcinoma de Células Renais/mortalidade , Everolimo/uso terapêutico , Feminino , França/epidemiologia , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Seleção de Pacientes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo
15.
World Neurosurg ; 133: e252-e258, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31505283

RESUMO

BACKGROUND: Selection of appropriate treatment for patients with recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate and acceptable toxicity using fractionated stereotactic radiosurgery (FSRS) in patients with locally recurrent large BM. The aim of this study was to evaluate efficacy and toxicity of FSRS with bevacizumab as a new salvage treatment for locally recurrent BM with previous high-dose irradiation. METHODS: Patients with recurrent BM previously irradiated were enrolled. Salvage FSRS dose was 9.5-29 Gy (2-5 fractions) with 62%-75% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. Bevacizumab was prescribed for 4 cycles (5 mg/kg, every 3 weeks). The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (Karnofsky performance scale), imaging response (magnetic resonance imaging) and treatment-related adverse events. RESULTS: From December 2009 to October 2016, 24 patients were enrolled. The 1-year overall survival after salvage stereotactic radiosurgery was 87.5%. Twenty-three (96%) patients had a positive imaging response with a T2 volume reduction range of 6-22 cm3 (median 14 cm3, P = 0.032, paired t test). Significant clinical improvement was achieved (best Karnofsky performance scale score, P < 0.05, paired t test). Grade 1/2 fatigue was observed in 8 (33%) patients. Grade 3 fatigue and headache occurred in 1 patient. CONCLUSIONS: FSRS with adjuvant bevacizumab treatment showed favorable clinical and radiologic control as a salvage treatment regimen. The diagnoses of radiation necrosis and local recurrence after salvage FSRS warrant further study.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma/secundário , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Carcinoma/cirurgia , Terapia Combinada , Irradiação Craniana , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos
16.
J Cancer Res Clin Oncol ; 146(3): 659-670, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31754832

RESUMO

BACKGROUND: The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status. METHODS: We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified for O6-methylguanine DNA methyltransferase (MGMT) status and crossover to bevacizumab or alkylators at further progression. RESULTS: Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agents at first recurrence was longer than with bevacizumab (11.1 versus 7.4 months, p < 0.001). The use of alkylators was associated with longer PRS-1 for patients with a methylated versus unmethylated MGMT promoter (p = 0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in patients receiving alkylating chemotherapy compared to bevacizumab for patients with methylated (p < 0.001) or unmethylated MGMT promoter (p = 0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p = 0.002). CONCLUSIONS: This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of MGMT promoter methylation.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Glioblastoma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Intervalo Livre de Progressão , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética , Adulto Jovem
17.
Crit Rev Oncol Hematol ; 145: 102823, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31783291

RESUMO

We conducted a systemic search of several databases for randomized controlled trials (RCTs) that reported efficacy and safety outcomes of drugs for left-sided and right-sided metastatic colorectal cancer (mCRC), to identify the best available treatment. A network meta-analysis with mixed comparisons was created to interpret the best treatment option using the surface under the cumulative ranking curve. In the left-sided rat sarcoma (RAS) wild-type (WT) mCRC patients, bevacizumab, panitumumab, or cetuximab with chemotherapy groups showed a significantly better objective response rate than the chemotherapy alone group. The progression-free survival (PFS) and overall survival were better with panitumumab or cetuximab with chemotherapy than with chemotherapy alone. In the right-sided RAS WT mCRC patients, PFS for bevacizumab with chemotherapy was significantly better than that for cetuximab with chemotherapy. Cetuximab, closely followed by panitumumab, is the most effective treatment in left-sided RAS WT mCRC. Bevacizumab is more effective in right-sided mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Anticorpos Monoclonais , Bevacizumab , Cetuximab , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Lateralidade Funcional , Humanos , Meta-Análise em Rede
18.
J Cancer Res Clin Oncol ; 146(2): 493-501, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31691872

RESUMO

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


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Prognóstico , Estudos Retrospectivos
19.
Klin Monbl Augenheilkd ; 237(1): 62-70, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-30736077

RESUMO

BACKGROUND: Trabeculectomy for the surgical reduction of internal eye pressure is an established procedure, but the principle limitations are in postoperative wound healing. Various antimetabolites are regularly used to avoid postoperative subconjunctival scarring. The present study investigates whether the combination of an Ologen implant with bevacizumab can modify the rates of success and/or complications during trabeculectomy. METHODS: Three different groups of patients were evaluated in which trabeculectomy was performed with mitomycin C, either alone (group 1) or in combination with an Ologen implant (group 2) or with an Ologen implant with bevacizumab (group 3). The success and failure rates, changes in tension, postoperative complications and postoperative revision for pressure regulation were evaluated. The follow-up was 12 months for all eyes. RESULTS: A total of 130 eyes in 130 patients (mean age 67.74 ± 12.16 years). The number of substances applied preoperatively to reduce intraocular pressure was 2.89 ± 0.98 and the internal ocular pressure was 21.74 ± 5.49 mmHg. Twelve months postoperatively; the mean pressure was 13.14 ± 3.71 mmHg. The greatest absolute success rate (= IOD ≤ 15 mmHg without antiglaucoma medication) was in the group with exclusive goniotrepanation + mitomycin C (MMC; 72.5%), followed by the groups with Ologen (67.5%) and Ologen + bevacizumab (63.6%). The greatest failure rate (= IOD > 15 mmHg) was in the Ologen bevacizumab group (17.3%), followed by the pure Ologen group with 22.5% and the pure trabeculectomy group (12.3%). There were no significant differences in the success and failure rates. There were no serious intra- or postoperative complications in any group. The number of patients for whom it was necessary to loosen the traction thread was significantly lower in the sole Ologen group (p = 0.02). There were also no significant differences between the groups with respect to revisions. CONCLUSION: Using Ologen as drug depot for bevacizumab in a trabeculectomy (TE) with MMC is a safe and active surgical method without an increased risk of complications in comparison to pure TE with MMC or TE with MMC and Ologen implant. After 12 months, this treatment exhibited no significant advantages.


Assuntos
Bevacizumab , Glaucoma , Trabeculectomia , Idoso , Bevacizumab/administração & dosagem , Colágeno/uso terapêutico , Glaucoma/terapia , Humanos , Pressão Intraocular , Pessoa de Meia-Idade , Mitomicina , Resultado do Tratamento
20.
Eur J Ophthalmol ; 30(1): 66-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30618282

RESUMO

BACKGROUND: Systemic complications of intravitreal anti-vascular endothelial growth factor agents are relatively uncommon but highly significant. OBJECTIVES: Primary objective: To assess the risk for thromboembolic events following intravitreal bevacizumab injection in neovascular age-related macular degeneration patients by a large population-based study. Secondary objective: To analyze the association between injection frequency and the risk for thromboembolic events, the time interval between the injection and the thromboembolic events, and the influence of chronic diseases on complications rate. DESIGN: A retrospective cohort study. METHODS: Consecutive neovascular age-related macular degeneration patients receiving intravitreal bevacizumab at Soroka University Medical Center from December 2005 to December 2013 were included. Thromboembolic events analyzed included acute coronary syndrome, acute myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. The thromboembolic event rate was compared 2 years prior and 2 years after the initial intravitreal bevacizumab injection. RESULTS: A total of 2102 patients were included. Acute coronary syndrome and stroke rate were higher 2 years after intravitreal bevacizumab (p = 0.03 and p = 0.01, respectively). No statistical significant difference was found for the rest of thromboembolic events. Patients older than 80 years and patients receiving less than six intravitreal bevacizumab injections were more likely to experience stroke. Patients with known cardiovascular risk factors before starting injections did not develop significant more thromboembolic events. CONCLUSION: In our study population, patients treated with intravitreal bevacizumab were significantly more likely to experience stroke during 2 years after first injection.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Neovascularização de Coroide/tratamento farmacológico , Tromboembolia/induzido quimicamente , Degeneração Macular Exsudativa/tratamento farmacológico , Síndrome Coronariana Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neovascularização de Coroide/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Embolia Pulmonar/induzido quimicamente , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Tromboembolia/diagnóstico , Tromboembolia/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Trombose Venosa/induzido quimicamente , Degeneração Macular Exsudativa/fisiopatologia
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