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1.
Eur J Cancer ; 143: 101-112, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33296830

RESUMO

BACKGROUND: Pancreatic cancer (PC) ranks among the deadliest malignancies worldwide. In the MPACT study, first-line nab-paclitaxel plus gemcitabine (nab-P/G) demonstrated activity (median overall survival [OS], 8.7 months) and tolerability in patients with metastatic PC (mPC). However, the clinical evidence of nab-P/G in the elderly (>70 years), who account for the majority of patients with mPC, is limited. This is the first prospective, multicentre, non-interventional study evaluating the tolerability and effectiveness of nab-P/G in younger (≤70 years) versus elderly (>70 years) patients with mPC in the daily clinical routine. METHODS: Eligible patients with mPC were treated with nab-P/G and observed until disease progression or unacceptable toxicity. The primary objectives were safety and tolerability of nab-P/G, and the secondary objectives were efficacy and real-life dosing. RESULTS: A total of 317 patients with mPC (median age, 70 years) were recruited, of which 299, aged ≤70 (n = 162) and >70 (n = 137) years, were eligible for analysis. Baseline characteristics and the safety profile were comparable between the groups. However, fatigue (22.8% versus 13.0%) and decreased appetite (8.8% versus 1.2%) were more frequent in elderly patients. Younger versus elderly patients equally benefited in terms of objective response rate (36% versus 48%), median progression-free survival (5.6 versus 5.5 months; hazard ratio [HR] = 1.03; p = 0.81) and OS (10.6 versus 10.2 months; HR = 0.89; p = 0.4). In addition, the median treatment duration (5 versus 4 cycles), relative dose intensity (70% versus 74%) or reasons for treatment discontinuation were similar. Most patients (56.2% versus 47.4%) benefited from a second-line therapy. CONCLUSION: This prospective real-world analysis confirms the feasibility and tolerability of nab-P/G treatment and reveals OS data similar for younger patients and elderly patients aged >70 years. CLINICALTRIALS. GOV REGISTRATION: NCT02555813. AUSTRIAN NIS REGISTRY: NIS005071.


Assuntos
Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Albuminas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Paclitaxel/farmacologia , Neoplasias Pancreáticas/patologia
2.
Breast Cancer Res ; 21(1): 19, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704493

RESUMO

BACKGROUND: Patients with early breast cancer (EBC) achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) have a favorable prognosis. Breast surgery might be avoided in patients in whom the presence of residual tumor can be ruled out with high confidence. Here, we investigated the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) in predicting pCR and long-term outcome after NACT. METHODS: Patients with EBC, including patients with locally advanced disease, who had undergone CE-MRI after NACT, were retrospectively analyzed (n = 246). Three radiologists, blinded to clinicopathologic data, reevaluated all MRI scans regarding to the absence (radiologic complete remission; rCR) or presence (no-rCR) of residual contrast enhancement. Clinical and pathologic responses were compared categorically using Cohen's kappa statistic. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Overall rCR and pCR (no invasive tumor in the breast and axilla (ypT0/is N0)) rates were 45% (111/246) and 29% (71/246), respectively. Only 48% (53/111; 95% CI 38-57%) of rCR corresponded to a pCR (= positive predictive value - PPV). Conversely, in 87% (117/135; 95% CI 79-92%) of patients, residual tumor observed on MRI was pathologically confirmed (= negative predictive value - NPV). Sensitivity to detect a pCR was 75% (53/71; 95% CI 63-84%), while specificity to detect residual tumor and accuracy were 67% (117/175; 95% CI 59-74%) and 69% (170/246; 95% CI 63-75%), respectively. The PPV was significantly lower in hormone-receptor (HR)-positive compared to HR-negative tumors (17/52 = 33% vs. 36/59 = 61%; P = 0.004). The concordance between rCR and pCR was low (Cohen's kappa - 0.1), however in multivariate analysis both assessments were significantly associated with RFS (rCR P = 0.037; pCR P = 0.033) and OS (rCR P = 0.033; pCR P = 0.043). CONCLUSION: Preoperative CE-MRI did not accurately predict pCR after NACT for EBC, especially not in HR-positive tumors. However, rCR was strongly associated with favorable RFS and OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Meios de Contraste/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neoplasia Residual , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Adulto Jovem
3.
Lancet Oncol ; 20(3): 339-351, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30795951

RESUMO

BACKGROUND: In postmenopausal women with hormone receptor-positive, early-stage breast cancer, treatment with adjuvant aromatase inhibitors is the standard of care, but it increases risk for osteoporosis and fractures. Results from the ABCSG-18 trial showed that use of denosumab as an adjuvant to aromatase inhibitor therapy significantly reduced clinical fractures. Disease-free survival outcomes from ABCSG-18 have not yet been reported. METHODS: Postmenopausal patients with early, hormone receptor-positive, non-metastatic adenocarcinoma of the breast, who had completed their initial adjuvant treatment pathway (surgery, radiotherapy, or chemotherapy, or a combination) and were receiving adjuvant aromatase inhibitors, were enrolled at 58 trial centres in Austria and Sweden into this prospective, double-blind, placebo-controlled, phase 3 trial. With permuted block randomisation (block sizes 2 and 4, stratified by previous aromatase inhibitor use, total lumbar spine bone mineral density score at baseline, and type of centre), patients were assigned (1:1) to receive subcutaneous denosumab (60 mg) or matching placebo every 6 months during aromatase inhibitor therapy. The primary endpoint (previously reported) was the time to first clinical fracture after randomisation. The secondary endpoint reported here is disease-free survival (defined as time from randomisation to first evidence of local or distant metastasis, contralateral breast cancer, secondary carcinoma, or death from any cause) in the intention-to-treat population. This study is registered with EudraCT (number 2005-005275-15) and ClinicalTrials.gov (number NCT00556374), and is ongoing for long-term follow-up. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled and randomly assigned; 1711 to the denosumab group and 1709 to the placebo group (with five others withdrawing consent). After a median follow-up of 73 months (IQR 58-95), 240 (14·0%) patients in the denosumab and 287 (16·8%) in the placebo group had disease-free survival events. Disease-free survival was significantly improved in the denosumab group versus the placebo group (hazard ratio 0·82, 95% CI 0·69-0·98, Cox p=0·0260; descriptive analysis, without controlling for multiplicity). In the denosumab group, disease-free survival was 89·2% (95% CI 87·6-90·8) at 5 years and 80·6% (78·1-83·1) at 8 years of follow-up, compared with 87·3% (85·7-89·0) at 5 years and 77·5% (74·8-80·2) and 8 years in the placebo group. No independently adjudicated cases of osteonecrosis of the jaw or confirmed atypical femoral fractures were recorded. The total number of adverse events was similar in the denosumab group (1367 [including 521 serious] adverse events) and the placebo group (1339 [515 serious]). The most common serious adverse events were osteoarthritis (62 [3·6%] of 1709 in the denosumab group vs 58 [3·4%] of 1690 in the placebo group), meniscus injury (23 [1·3%] vs 24 [1·4%]), and cataract (16 [0·9%] vs 28 [1·7%]). One (<0·1%) treatment-related death (due to pneumonia, septic kidney failure, and cardiac decompensation) occurred in the denosumab group. INTERPRETATION: Denosumab constitutes an effective and safe adjuvant treatment for patients with postmenopausal hormone receptor-positive early breast cancer receiving aromatase inhibitor therapy. FUNDING: Amgen.


Assuntos
Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Denosumab/administração & dosagem , Idoso , Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Denosumab/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/efeitos dos fármacos , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética
4.
BMC Cancer ; 18(1): 1074, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400780

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy has been approved for TNBC and cytotoxic agents remain the mainstay of treatment. Ixazomib is a selective and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrated. Clinical data are available for carboplatin plus bortezomib in metastatic ovarian and lung cancers showing remarkable antitumor activity and good tolerability (Mol Cancer 11:26 2012, J Thorac Oncol 4:87-92 2009, J Thorac Oncol 7:1032-1040, 2012). Based on this evidence, the phase I/II MBC-10 trial will evaluate the toxicity profile and efficacy of the second-generation proteasome inhibitor ixazomib in combination with carboplatin in patients with advanced TNBC. METHODS: Patients with metastatic TNBC pretreated with at least one prior line of chemotherapy for advanced disease with a confirmed disease progression and measurable disease according to RECIST criteria 1.1 are eligible for this study. Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle. The phase I part of this study utilizes an alternate dose escalation accelerated titration design. After establishing the maximum tolerated dose (MTD), the efficacy and safety of the combination will be further evaluated (phase II, including 41 evaluable patients). All patients will continue on study drugs until disease progression, unacceptable toxicity or discontinuation for any other reason. Primary endpoint of the phase II is overall response rate, secondary endpoints include progression-free survival, safety, and quality of life. This trial is open for patient enrollment since November 2016 in six Austrian cancer centers. Accrual is planned to be completed within 2 years. DISCUSSION: Based on preclinical and clinical findings an ixazomib and carboplatin combination is thought to be effective in metastatic TNBC patients. The MBC-10 trial is accompanied by a broad biomarker program investigating predictive biomarkers for treatment response and potential resistance mechanisms to the investigational drug combination. TRIAL REGISTRATION: EudraCT Number: 2016-001421-13 received on March 31, 2016, ClinicalTrials.gov Identifier: NCT02993094 first posted on December 15, 2016. This trial was registered prospectively.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos de Boro/administração & dosagem , Carboplatina/administração & dosagem , Glicina/análogos & derivados , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Áustria , Compostos de Boro/efeitos adversos , Bortezomib/administração & dosagem , Carboplatina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Qualidade de Vida , Neoplasias de Mama Triplo Negativas/patologia
5.
Cancer Med ; 7(12): 5962-5972, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30415507

RESUMO

BACKGROUND: There is a well-known correlation between obesity, sedentary lifestyle, and breast cancer incidence and outcome. The Arbeitsgemeinschaft Medikamentöse Tumortherapie (AGMT) exercise study was a multicenter, randomized clinical trial and assessed the feasibility and efficacy of physical training in 50 breast cancer patients undergoing aromatase inhibitor treatment. METHODS: Postmenopausal, estrogen receptor-positive breast cancer patients under aromatase inhibitor treatment were randomized 1:1 to counseling and unsupervised training for 48 weeks (unsupervised arm) or counseling and a sequential training (supervised arm) with a supervised phase (24 weeks) followed by unsupervised physical training (further 24 weeks). Primary endpoint was the individual maximum power output on a cycle ergometer after 24 weeks of exercise. A key secondary endpoint was the feasibility of achieving 12 METh/week (metabolic equivalent of task hours per week). RESULTS: Twenty-three patients (92%) in the unsupervised arm and 19 patients (76%) in the supervised arm with early-stage breast cancer completed the study. After 24 weeks, the supervised arm achieved a significantly higher maximum output in watt (mean 132 ±  standard deviation [SD] 34; 95% confidence interval [CI] 117-147) compared to baseline (107 ± 25; 95%CI 97-117; P = 0.012) with a numerically higher output than the unsupervised arm (week 24 115 ± 25; 95%CI 105-125; P = 0.059). Significantly higher METh/week was reported in the supervised arm compared to the unsupervised arm during the whole study period (week 1-24 unsupervised: 18.3 (7.6-58.3); supervised: 28.5 (6.7-40.1); P = 0.043; week 25-48; P = 0.041)). CONCLUSION: This trial indicates that patients in an exercise program achieve higher fitness levels during supervised than unsupervised training.


Assuntos
Neoplasias da Mama/terapia , Terapia por Exercício/métodos , Cooperação do Paciente , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade
6.
Memo ; 10(4): 237-239, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29250203

RESUMO

At this year's ASCO annual meeting several important studies in the field of gynecological cancer were presented. Here we report a personal selection of the most interesting and clinically relevant data.

7.
JAMA ; 316(18): 1888-1896, 2016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27825007

RESUMO

Importance: Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. Objective: To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. Design, Setting, and Participants: A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. Interventions: Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. Main Outcomes and Measures: The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. Results: Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0.63-0.99; P = .04; 5-year EFS, 86.7% vs 82.1%). The groups did not differ in OS (HR, 0.77; 95% CI, 0.57-1.05; P = .09; 5-year OS, 92.1% vs 90.2%) or DDFS (HR, 0.83; 95% CI, 0.64-1.08; P = .17; 5-year DDFS, 89.4% vs 86.7%). Grade 3 or 4 nonhematologic toxic effects occurred in 527 (52.6%) in the tailored dose-dense group and 366 (36.6%) in the control group. Conclusions and Relevance: Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence-free survival. Nonhematologic toxic effects were more frequent in the tailored dose-dense group. Trial Registration: clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Áustria , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Alemanha , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Qualidade de Vida , Suécia , Taxoides/administração & dosagem
8.
Memo ; 9: 82-84, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27429660

RESUMO

Increased numbers of tumour infiltrating T­cells have long been associated with a better prognosis in ovarian cancer, which has led to the general assumption of a relevant impact of T­cellular anti-tumour immunity in this disease. As a consequence of this knowledge, a multitude of immunologic therapies has emerged over the past years. Although some reports could evidence a successful induction of anti-tumour T­cells, in general, these attempts did not translate into clinically significant activity. As has already been shown in other tumour entities, immune checkpoint blockade - mainly antibodies directed against PD-1 and PD-L1 - could possibly become a real "game changer" in ovarian cancer in the future.

9.
Memo ; 9: 17-19, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27069512

RESUMO

The probability of developing breast cancer increases with age. Therefore, more than 50 % of women with breast cancer are older than 65 years at the time of diagnosis. However, elderly patients are often undertreated and clinical trials for elderly patients in the adjuvant setting are lacking. Elderly patients who are otherwise fit should receive the standard treatment regimen independent of age. Endocrine therapy should not be withheld from patients by age alone. Thus, there are more adverse events in the elderly population. The decision on adjuvant chemotherapy should be made taking into consideration the patient's comorbidities and frailty. A less toxic single-agent regimen may influence overall survival, but are associated with much less toxicity. Trastuzumab has a similar effect in elderly patients to that in younger patients. The risk of cardiotoxicity should be carefully considered in each patient.

10.
Int J Mol Sci ; 17(2)2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26821018

RESUMO

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan(®) Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)(®) microarrays from Agilent(®) was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort.


Assuntos
Neoplasias da Mama/genética , Expressão Gênica , Genes Essenciais , MicroRNAs/genética , Neoplasias da Mama/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/normas , Humanos , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Sequência com Séries de Oligonucleotídeos/normas
11.
Lancet ; 386(9992): 433-43, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26040499

RESUMO

BACKGROUND: Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. METHODS: In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. INTERPRETATION: Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. FUNDING: Amgen.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/complicações , Fraturas Ósseas , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Áustria , Densidade Óssea/fisiologia , Neoplasias da Mama/tratamento farmacológico , Denosumab , Método Duplo-Cego , Feminino , Fraturas Ósseas/complicações , Fraturas Ósseas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Suécia , Resultado do Tratamento
12.
Anticancer Res ; 35(1): 517-21, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25550597

RESUMO

BACKGROUND: Trastuzumab, one important treatment option for HER2-positive metastatic breast cancer (MBC) is limited by its cardiotoxic potential. Lapatinib and pegylated liposomal doxorubicin (PLD) represent a cardiosparing alternative that can cross the blood brain barrier. This is important, because one third of breast cancer patients develop brain metastases. PATIENTS AND METHODS: We included 24 patients with HER2-positive MBC progressing under trastuzumab. They received 1,250 mg lapatinib daily until progression plus PLD (40 mg/m(2)) every 4 weeks for maximal 6 cycles. The primary end-point was the overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), 1-year PFS and 1-year OS rates. RESULTS: ORR was 54%. Median PFS was 5.8 and median OS 23.3 months. The one-year PFS rate was 27% and 1-year OS rate 76%. CONCLUSION: Lapatinib-plus-PLD is active and safe in HER2-positive MBC, especially suitable for patients with cardiological risk or brain metastases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Lapatinib , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Quinazolinas/administração & dosagem , Trastuzumab , Resultado do Tratamento
13.
Anticancer Drugs ; 25(7): 848-53, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24667659

RESUMO

Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile.


Assuntos
Antineoplásicos/uso terapêutico , Leiomiossarcoma/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Feminino , Humanos , Leiomiossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Estudos Retrospectivos , Neoplasias de Tecidos Moles/patologia , Sorafenibe , Adulto Jovem
14.
Clin Cancer Res ; 20(5): 1298-305, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24520097

RESUMO

PURPOSE: To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrine-responsive breast cancer patients. EXPERIMENTAL DESIGN: The PAM50 assay was performed on formalin-fixed paraffin-embedded whole-tumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters. RESULTS: PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: ΔLRχ(2) 15.32, P < 0.001; ROR-based risk groups: ΔLRχ(2) 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease. CONCLUSION: PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pós-Menopausa , Prognóstico , Resultado do Tratamento
15.
Anticancer Res ; 34(1): 227-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24403467

RESUMO

BACKGROUND: Several phase-III studies have shown improvements in terms of progression-free survival (PFS) with bevacizumab when added to chemotherapy in advanced breast cancer. However, the extent of improvement varied and none of the trials showed benefit in terms of overall survival (OS). PATIENTS AND METHODS: All patients with metastatic breast cancer treated with bevacizumab at our Institution between 2005 and 2011 were retrospectively analyzed. A control group was matched according to the following variables: receptor status, treatment line, type of chemotherapy, presence of visceral disease and age. RESULTS: All 212 patients were evaluable for toxicity, and 198 for response; 430 controls allowed a complete matching for 85 bevacizumab-treated patients. The addition of bevacizumab to chemotherapy significantly prolonged PFS (9.3 vs. 7.6 months, hazard ratio [HR]=0.70, 95% confidence interval [CI]=0.51-0.97, p=0.031) and OS (28.9 vs. 22.6 months, HR=0.67, 95% CI=0.45-0.99, p=0.043). Clinical benefit rate (overall response rate + stable disease for at least six months) was significantly better in the bevacizumab group (75% vs. 59%, p=0.002), while ORR did not differ significantly (48% vs. 35%, p=0.21). Patients developing hypertension during treatment had a more favourable outcome (PFS 13.7 vs. 6.6 months, HR=0.34, 95% CI=0.23-0.49 p<0.001; 2-year OS 78% vs. 30%, HR=0.20, 95% CI=0.12-0.35, p<0.001). CONCLUSION: Bevacizumab in addition to chemotherapy prolonged PFS and OS in a non-selected, partly intensively pre-treated breast cancer population. Hypertension induced by bevacizumab predicted therapy efficacy.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Hipertensão/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Hipertensão/induzido quimicamente , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
16.
J Clin Oncol ; 30(7): 722-8, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22271481

RESUMO

PURPOSE: Anastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor-positive breast cancer. The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients. PATIENTS AND METHODS: Endocrine receptor-positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated. RESULTS: Information from 3,714 patients, including 17,563 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment. CONCLUSION: Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Áustria , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Estudos Prospectivos , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Triazóis/administração & dosagem , Triazóis/efeitos adversos
17.
BMC Cancer ; 11: 373, 2011 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-21864402

RESUMO

BACKGROUND: In advanced breast cancer, multiple sequential lines of treatments are frequently applied. Pegylated liposomal doxorubicin (PLD) has a favourable toxicity profile and can be used in first or higher lines of therapy. PLD has demonstrated response activity even after prior anthracycline exposure. METHODS: 129 consecutive patients with advanced breast cancer, of whom the majority had been massively pretreated, received PLD as monotherapy within licensed approval, for which efficacy and toxicities were documented. RESULTS: In a routine therapy setting, PLD was administered in a slightly reduced dose (median, 40 mg/m2 per cycle). Response rate (complete and partial remission) was 26%, and stable disease was observed in 19% of patients. Progression-free (PFS) and overall survival (OS) were 5.8 months and 14.2 months, respectively. There was no difference in terms of response and PFS, no matter if patients had already received anthracycline treatment. Interestingly, PFS proved similar regardless whether PLD was administered as palliative therapy in first, second or third line. Furthermore, PFS and OS were similar in patients with response or stable disease, underscoring the view that disease stabilization is associated with a profound clinical benefit. The most common side effects reported were palmar-plantar erythrodysesthesia (17%), exanthema (14%) and mucositis (12%). CONCLUSIONS: Efficacy and toxicity data in these "real life" patients permit the conclusion that PLD is a valuable option in the treatment of advanced breast cancer even in heavily pretreated patients.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/análogos & derivados , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Áustria , Neoplasias da Mama/patologia , Estudos de Coortes , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Cuidados Paliativos , Polietilenoglicóis/efeitos adversos
18.
Lancet Oncol ; 12(7): 631-41, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21641868

RESUMO

BACKGROUND: Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid. METHODS: ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I-II) breast cancer receiving goserelin (3.6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing. FINDINGS: At a median follow-up of 62 months (range 0-114.4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid reduced risk of disease-free survival events overall (HR 0.68, 95% CI 0.51-0.91; p=0.009), although the difference was not significant in the tamoxifen (HR 0.67, 95% CI 0.44-1.03; p=0.067) and anastrozole arms (HR 0.68, 95% CI 0.45-1.02; p=0.061) assessed separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without; HR 0.67, 95% CI 0.41-1.07; p=0.09). There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone (HR 1.08, 95% CI 0.81-1.44; p=0.591), but overall survival was worse with anastrozole than with tamoxifen (46 vs 27 deaths; HR 1.75, 95% CI 1.08-2.83; p=0.02). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was reported in 601 patients (33%; 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%; 192 vs 169), headache in 280 (16%; 147 vs 133), and arthralgia in 266 (15%; 145 vs 121). INTERPRETATION: Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen. There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer. FUNDING: AstraZeneca; Novartis.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Adulto , Anastrozol , Antineoplásicos Hormonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitrilas/uso terapêutico , Pré-Menopausa , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Triazóis/uso terapêutico , Ácido Zoledrônico
19.
J Clin Oncol ; 29(19): 2653-9, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21555684

RESUMO

PURPOSE: Aromatase inhibitors are effective as endocrine treatment for patients with hormone receptor-positive breast cancer. According to the hypothesis that overweight patients have higher levels of aromatase enzyme availability, we investigated the influence of body mass index (BMI) on the efficacy of adjuvant endocrine therapy in premenopausal patients in a retrospective analysis of the Austrian Breast and Colorectal Cancer Study Group (ABCSG) 12 trial. PATIENTS AND METHODS: ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg subcutaneously every 28 days) in combination with anastrozole or tamoxifen with or without zoledronic acid (4 mg intravenously every 6 months) in premenopausal women with endocrine-responsive breast cancer. BMI was calculated using the prospectively collected data on patients' height and weight at study entry. BMI categories have been differentiated according to the WHO definition. RESULTS: Overweight patients treated with anastrozole had a 60% increase in the risk of disease recurrence (hazard ratio [HR], 1.60; 95% CI, 1.06 to 2.41; P = .02) and more than a doubling in the risk of death (HR, 2.14; 95% CI, 1.17 to 3.92; P = .01) compared with normal weight patients treated with anastrozole. In the overweight group, patients treated with anastrozole had a nearly 50% increase in the risk of disease recurrence (HR, 1.49; 95% CI, 0.93 to 2.38; P = .08) and a three-fold increase in the risk of death (HR, 3.03; 95% CI, 1.35 to 6.82; P = .004) compared with patients treated with tamoxifen. CONCLUSION: BMI significantly impacts on the efficacy of anastrozole plus goserelin in premenopausal patients with breast cancer, probably through influencing aromatase availability and/or ovarian suppression by goserelin.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Gosserrelina/administração & dosagem , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Adulto , Anastrozol , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Risco , Tamoxifeno/farmacologia , Resultado do Tratamento
20.
Oncology ; 80(1-2): 34-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21606662

RESUMO

OBJECTIVE: Temsirolimus inhibits the mammalian target of rapamycin with demonstrated efficacy in patients with advanced renal cell cancer. PATIENTS AND METHODS: We present a retrospective analysis of our single-center experience with temsirolimus in patients pretreated with sunitinib, sorafenib or everolimus. Sixteen patients were treated within our center starting in December 2006 until September 2009. The majority of patients (14 of 16) had received a prior antiangiogenic pretreatment. We further analyzed the efficacy of subsequent treatment with temsirolimus in these patients. RESULTS: Stable disease could be achieved in 8 of 14 pretreated patients (57%). The duration of median progression-free survival was 10 weeks (range 1-43). Especially patients with a good response to previous antiangiogenic treatment, a good overall condition and a low Memorial Sloan Kettering Cancer Center (MSKCC) score benefited from subsequent treatment with temsirolimus. We did not see any complete or partial response meeting the World Health Organization criteria. Temsirolimus was well tolerated. CONCLUSION: Temsirolimus appears to be an effective and well-tolerated substance in the treatment of patients with a good performance status, low MSKCC score and stable disease under previous antiangiogenic treatment in advanced renal cell cancer. However, its use is highly questionable in pretreated patients with a poor performance score and a high MSKCC score.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Sirolimo/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Inibidores da Angiogênese/uso terapêutico , Benzenossulfonatos/administração & dosagem , Carcinoma de Células Renais/cirurgia , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Everolimo , Feminino , Humanos , Indóis/administração & dosagem , Avaliação de Estado de Karnofsky , Neoplasias Renais/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Metástase Neoplásica , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/administração & dosagem , Pirróis/administração & dosagem , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sorafenibe , Sunitinibe , Trombocitopenia/induzido quimicamente
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