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1.
Int J Cancer ; 155(6): 1045-1052, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703351

RESUMO

A diagnosis of brain metastasis (BM) significantly affects quality of life in patients with metastatic renal cell cancer (mRCC). Although systemic treatments have shown efficacy in mRCC, active surveillance (AS) is still commonly used in clinical practice. In this single-center cohort study, we assessed the impact of different initial treatment strategies for metastatic RCC (mRCC) on the development of BM. All consecutive patients diagnosed with mRCC between 2011 and 2022 were included at the Erasmus MC Cancer Institute, the Netherlands, and a subgroup of patients with BM was selected. In total, 381 patients with mRCC (ECM, BM, or both) were identified. Forty-six patients had BM of whom 39 had metachronous BM (diagnosed ≥1 month after ECM). Twenty-five (64.1%) of these 39 patients with metachronous BM had received prior systemic treatment for ECM and 14 (35.9%) patients were treatment naive at BM diagnosis. The median BM-free survival since ECM diagnosis was significantly longer (p = .02) in previously treated patients (29.0 [IQR 12.6-57.0] months) compared to treatment naive patients (6.8 [IQR 1.0-7.0] months). In conclusion, patients with mRCC who received systemic treatment for ECM prior to BM diagnosis had a longer BM-free survival as compared to treatment naïve patients. These results emphasize the need for careful evaluation of treatment strategies, and especially AS, for patients with mRCC.


Assuntos
Neoplasias Encefálicas , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/terapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Masculino , Feminino , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Estudos Retrospectivos , Países Baixos/epidemiologia
2.
EBioMedicine ; 102: 105074, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38507877

RESUMO

BACKGROUND: Sotorasib given after immunotherapy could put patients at increased risk of hepatotoxicity. Therefore, there is a need to gain insight into the potential correlation between anti-PD-(L)1 treatment, anti-PD-(L)1 concentrations, sotorasib concentrations, and the incidence of hepatotoxicity during sotorasib. METHODS: Patients with KRASG12C-mutated NSCLC treated with sotorasib were prospectively enrolled in our biomarker cohort study (NCT05221372). Plasma samples were collected prior and during sotorasib treatment for anti-PD-1 and sotorasib concentrations. ALT/AST/ALP/GGT increases were collected prospectively and graded according to CTCAEv5.0. Severe hepatotoxicity was defined as grade ≥3 ALT/AST/ALP/GGT increase. FINDINGS: Of the 91 included patients, 80 (88%) received prior anti-PD-(L)1. Prior anti-PD-(L)1 and prior immune-related hepatotoxicity were associated with a higher incidence of severe hepatotoxicity (35% versus 0%, p = 0.016 and 75% versus 31%, p = 0.019, respectively). Patients with an interval of ≤6 weeks between anti-PD-(L)1 and sotorasib (n = 18) had a significantly higher incidence of severe hepatotoxicity than those with a 6-12 week (n = 24) and ≥12 week (n = 38) interval (83% versus 33% versus 13%, respectively, p < 0.0001). Sotorasib trough concentrations did not differ significantly between those with or without severe hepatotoxicity (106 versus 126 ng/mL, p = 0.16). Pembrolizumab concentrations were higher in those with severe hepatotoxicity versus those without (25.6 versus 6.1 µg/mL, p < 0.0001). INTERPRETATION: In this preliminary prospective study, sotorasib after PD-(L)1 blockade was associated with severe hepatotoxicity, especially in patients with a short interval between treatments, prior immune-related hepatitis and higher anti-PD-1 plasma concentrations. Our results suggest a minimum interval of 6 weeks between anti-PD-(L)1 and sotorasib to minimize the risk of hepatotoxicity. FUNDING: None.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doença Hepática Induzida por Substâncias e Drogas , Neoplasias Pulmonares , Piperazinas , Piridinas , Pirimidinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Coortes , Neoplasias Pulmonares/tratamento farmacológico , Estudos Prospectivos , Imunoterapia/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Proteínas Proto-Oncogênicas p21(ras) , Mutação
3.
NPJ Breast Cancer ; 9(1): 63, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37543688

RESUMO

Tamoxifen may lead to bothersome side effects contributing to non-compliance and decreased quality of life. Patients searching for relief are increasingly turning to cannabinoids such as CBD-oil. However, CBD-oil might affect tamoxifen pharmacokinetics (PK) through CYP2D6 inhibition. The aims of this open-label, single-arm study were (1) to determine the PK profile of tamoxifen when using CBD-oil, and (2) to subsequently investigate whether CBD-oil has a beneficial influence on side effects. Study patients had to have steady-state endoxifen concentrations ≥16 nM (conservative threshold). PK sampling and side effect assessment was done at initiation of CBD-oil and 28 days thereafter. Bio-equivalence could be concluded if the 90% confidence interval (CI) for the difference in endoxifen AUC fell within the [-20%; +25%] interval. The effect of CBD-oil on side effects was evaluated using the FACT-ES questionnaire. Endoxifen AUC decreased after CBD-oil by 12.6% (n = 15, 90% CI -18.7%, -6.1%) but remained within bio-equivalence boundaries. The endocrine sub-scale of the FACT-ES improved clinically relevant with 6.7 points (n = 26, p < 0.001) and health-related quality of life improved with 4.7 points after using CBD (95% CI + 1.8, +7.6). We conclude that CBD-oil, if of good quality and with a dosage below 50 mg, does not have to be discouraged in patients using it for tamoxifen-related side effects. Clinical trial registration: International Clinical Trial Registry Platform (NL8786; https://www.who.int/clinical-trials-registry-platform ).

4.
Support Care Cancer ; 30(11): 9299-9306, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36071303

RESUMO

PURPOSE: Adequate integration of palliative care in oncological care can improve the quality of life in patients with advanced cancer. Whether such integration affects the use of diagnostic procedures and medical interventions has not been studied extensively. We investigated the effect of the implementation of a standardized palliative care pathway in a hospital on the use of diagnostic procedures, anticancer treatment, and other medical interventions in patients with incurable cancer at the end of their life. METHODS: In a pre- and post-intervention study, data were collected concerning adult patients with cancer who died between February 2014 and February 2015 (pre-PCP period) or between November 2015 and November 2016 (post-PCP period). We collected information on diagnostic procedures, anticancer treatments, and other medical interventions during the last 3 months of life. RESULTS: We included 424 patients in the pre-PCP period and 426 in the post-PCP period. No differences in percentage of laboratory tests (85% vs 85%, p = 0.795) and radiological procedures (85% vs 82%, p = 0.246) were found between both groups. The percentage of patients who received anticancer treatment or other medical interventions was lower in the post-PCP period (40% vs 22%, p < 0.001; and 42% vs 29%, p < 0.001, respectively). CONCLUSIONS: Implementation of a PCP resulted in fewer medical interventions, including anticancer treatments, in the last 3 months of life. Implementation of the PCP may have created awareness among physicians of patients' impending death, thereby supporting caregivers and patients to make appropriate decisions about medical treatment at the end of life. TRIAL REGISTRATION NUMBER: Netherlands Trial Register; clinical trial number: NL 4400 (NTR4597); date registrated: 2014-04-27.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Assistência Terminal , Adulto , Humanos , Cuidados Paliativos/métodos , Qualidade de Vida , Morte , Neoplasias/terapia , Assistência Terminal/métodos
5.
Clin Pharmacokinet ; 61(4): 527-537, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34786650

RESUMO

BACKGROUND: Endoxifen is the most important active metabolite of tamoxifen. Several retrospective studies have suggested a minimal or threshold endoxifen systemic concentration of 14-16 nM is required for a lower recurrence rate. The aim of this study was to investigate the feasibility of reaching a predefined endoxifen level of ≥ 16 nM (5.97 ng/mL) over time using therapeutic drug monitoring (TDM). METHODS: This prospective open-label intervention study enrolled patients who started treatment with a standard dose of tamoxifen 20 mg once daily for early breast cancer. An outpatient visit was combined with a TDM sample at 3, 4.5, and 6 months after initiation of the tamoxifen treatment. The tamoxifen dose was escalated to a maximum of 40 mg if patients had an endoxifen concentration < 16 nM. The primary endpoint of the study was the percentage of patients with an endoxifen level ≥ 16 nM at 6 months after the start of therapy compared with historical data, in other words, 80% of patients with endoxifen levels ≥ 16 nM with standard therapy. RESULTS: In total, 145 patients were included. After 6 months, 89% of the patients had endoxifen levels ≥ 16 nM, compared with a literature-based 80% of patients with endoxifen levels ≥ 16 nM at baseline (95% confidence interval 82-94; P = 0.007). In patients with an affected CYP2D6 allele, it was not always feasible to reach the predefined endoxifen level of ≥ 16 nM. No increase in tamoxifen-related adverse events was reported after dose escalation. CONCLUSION: This study demonstrated that it is feasible to increase the percentage of patients with endoxifen levels ≥ 16 nM using TDM. TDM is a safe strategy that offers the possibility of nearly halving the number of patients with endoxifen levels < 16 nM.


Assuntos
Neoplasias da Mama , Tamoxifeno , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Citocromo P-450 CYP2D6/metabolismo , Monitoramento de Medicamentos , Feminino , Hormônios , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos , Tamoxifeno/análogos & derivados
6.
Genes (Basel) ; 11(4)2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32230800

RESUMO

Cisplatin is a chemotherapeutic agent widely used for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin, dose-limiting acute kidney injury (AKI) occurs. Here, we assessed the association of 3 catechol-O-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) with increased cisplatin-induced nephrotoxicity. In total, 551 patients were genotyped for the 1947 G>A (Val158Met, rs4680), c.615 + 310 C>T (rs4646316), and c.616 - 367 C>T (rs9332377) polymorphisms. Associations between these variants and AKI grade ≥3 were studied. The presence of a homozygous variant of c.616-367C>T was associated with a decreased occurrence of AKI grade 3 toxicity (p = 0.014, odds ratio (OR) 0.201, 95% confidence interval (CI) (0.047-0.861)). However, we could not exclude the role of dehydration as a potential cause of AKI in 25 of the 27 patients with AKI grade 3, which potentially affected the results substantially. As a result of the low incidence of AKI grade 3 in this dataset, the lack of patients with a COMT variant, and the high number of patients with dehydration, the association between COMT variants and AKI does not seem clinically relevant.


Assuntos
Injúria Renal Aguda/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Catecol O-Metiltransferase/genética , Neoplasias/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Idoso , Cisplatino/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Pemetrexede/administração & dosagem , Prognóstico , Estudos Prospectivos
7.
Contemp Clin Trials ; 88: 105876, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676314

RESUMO

BACKGROUND: Surgery of GBM nowadays is usually performed under general anesthesia (GA) and resections are often not as aggressive as possible, due to the chance of seriously damaging the patient with a rather low life expectancy. A surgical technique optimizing resection of the tumor in eloquent areas but preventing neurological deficits is necessary to improve survival and quality of life in these patients. Awake craniotomy (AC) with the use of cortical and subcortical stimulation has been widely implemented for low-grade glioma resections (LGG), but not yet for GBM. AC has shown to increase resection percentage and preserve quality of life in LGG and could thus be of important value in GBM surgery. METHODS/DESIGN: This study is a prospective, multicenter, randomized controlled trial (RCT). Consecutive patients with a glioblastoma in or near eloquent areas (Sawaya grading II/III) will be 1:1 randomized to awake craniotomy or craniotomy under general anesthesia. 246 patients will be included in neurosurgical centers in the Netherlands and Belgium. Primary end-points are: 1) Postoperative neurological morbidity and 2) Proportion of patients with gross-total resections. Secondary end-points are: 1) Health-related quality of life; 2) Progression-free survival (PFS); 3) Overall survival (OS) and 4) Frequency and severity of Serious Adverse Effects in each group. Also, a cost-benefit analysis will be performed. All patients will receive standard adjuvant treatment with concomitant chemoradiotherapy. DISCUSSION: This RCT should demonstrate whether AC is superior to craniotomy under GA on neurological morbidity, extent of resection and survival for glioblastoma resections in or near eloquent areas. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03861299 Netherlands Trial Register (NTR): NL7589.


Assuntos
Anestesia Geral , Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Vigília , Neoplasias Encefálicas/diagnóstico por imagem , Craniotomia , Glioblastoma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Estudos Multicêntricos como Assunto , Intervalo Livre de Progressão , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida
8.
Pharmacogenomics ; 20(18): 1283-1290, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829834

RESUMO

Aim: The pharmacokinetics and pharmacodynamics of vemurafenib are characterized by a wide interpatient variability. Since multiple polymorphic enzymes and drug transporters are involved in vemurafenib pharmacokinetics, we studied associations of polymorphisms on vemurafenib-associated toxicities. Patients & methods: Prospectively collected samples of 97 melanoma patients treated with vemurafenib alone (n = 62) or in combination with cobimetinib (n = 35) were genotyped for ABCB1 (3435C>T), ABCG2 (421C>A, 34G>A) and CYP3A4 (*22, 15389C>T) polymorphisms. Associations between these variants and the incidence of toxicities were studied. Results:CYP3A4*22 was significantly associated with increased risk for grade ≥3 nausea, grade 1-4 hyperbilirubinemia, and cutaneous squamous cell carcinoma. ABCB1 3435C>T was a predictor for grade ≥3 toxicity. Conclusion: Genetic variants in CYP3A4 and ABCB1 are associated with vemurafenib-associated toxicities.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Citocromo P-450 CYP3A/genética , Melanoma/tratamento farmacológico , Proteínas de Neoplasias/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Melanoma/genética , Melanoma/patologia , Pessoa de Meia-Idade , Variantes Farmacogenômicos/genética , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Vemurafenib/administração & dosagem , Vemurafenib/efeitos adversos
9.
Eur J Cancer ; 121: 48-54, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542641

RESUMO

BACKGROUND: The interpretation of the presence of AR-V7 in circulating tumour cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) remains to be elucidated. AR-V7 may hold promise as a predictive biomarker, but there may be prognostic impact of AR-V7 positivity as well. To investigate the clinical value of AR-V7, we determined whether AR-V7 detection in CTCs in patients with mCRPC is associated with CTC counts and survival. METHODS: Between December 2011 and January 2019, three prospective clinical trials collected clinical data of patients with mCRPC, who progressed after docetaxel and/or enzalutamide or abiraterone. Baseline (and follow-up) blood samples were withdrawn determining CTC count and AR-V7 expression. The majority of patients started cabazitaxel as the next line of treatment after AR-V7 characterisation. RESULTS: A total of 127 samples were evaluable for the analysis of CTC count versus AR-V7 status. Although an association was observed between AR-V7 and CTC count in all patients with mCRPC (p = 0.017), no such association was found in the prognostic unfavourable subgroup of patients with ≥5 CTCs. After adjusting for clinical prognostic factors, AR-V7 expression in CTCs was not associated with overall survival (hazard ratio = 1.33, 95% confidence interval = 0.81-2.15, p = 0.25). CONCLUSION: We found that AR-V7 expression in CTCs had no additional prognostic value in patients with mCRPC, mostly treated with cabazitaxel. In patients with mCRPC with a predefined worse prognosis of a higher CTC count (≥5), a predictive biomarker is an important unmet medical need. Prospective trials should investigate whether AR-V7 detection in CTCs may guide treatment selection for these adverse prognosis patients.


Assuntos
Biomarcadores Tumorais/sangue , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Receptores Androgênicos/sangue , Idoso , Biomarcadores Tumorais/metabolismo , Contagem de Células Sanguíneas , Ensaios Clínicos como Assunto/estatística & dados numéricos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/uso terapêutico
10.
J Clin Epidemiol ; 116: 146-149, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31449856

RESUMO

In 2012, Weijer et al published "The Ottawa Statement on the ethical design and conduct of cluster randomized trials". In 2015, we reflected on this statement and argued that three recommendations in this statement need to be further refined. Weijer and Taljaard have responded to our comments in this issue of the journal. They agree with one of the proposed revisions but not with two others. In this commentary, we argue that the main reason why there is disagreement about two of our refinements is that we have different views on the moral and legal status of the health care workers as "research participants" in cluster randomized trials (CRTs). In this commentary, we clarify misunderstandings about our view expressed in 2015 and elaborate on the positions of health care workers in CRTs. We argue that there is sufficient reason to doubt whether the rights and interests of health care workers (HCWs) should be protected by means of ethics guidance documents and laws on human subjects research. Their interests are protected in the first place by professional codes of conduct which ensure that they cannot provide substandard care. Furthermore, protection of HCWs by ethics guidance on human subjects research will create an enormous burden for principle investigators and research ethics committees. Further debate is essential to determine how the interests of HCWs in CRTs can be protected best.


Assuntos
Consentimento Livre e Esclarecido , Projetos de Pesquisa , Comitês de Ética em Pesquisa , Pessoal de Saúde , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Cancers (Basel) ; 11(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434336

RESUMO

(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles of circulating tumor cells (CTCs). (2) Methods: From 120 mCRPC patients, CellSearch enriched CTCs were obtained at baseline and after 6 weeks of cabazitaxel therapy. Furthermore, 91 genes associated with prostate cancer were measured in mRNA of these CTCs. (3) Results: In 114 mCRPC patients with an evaluable CTC count, the CTC count was independently associated with poor progression-free survival (PFS) and overall survival (OS) in multivariable analysis with other commonly used variables associated with outcome in mCRPC (age, prostate specific antigen (PSA), alkaline phosphatase, lactate dehydrogenase (LDH), albumin, hemoglobin), together with alkaline phosphatase and hemoglobin. A five-gene expression profile was generated to predict for outcome to cabazitaxel therapy. However, even though this signature was associated with OS in univariate analysis, this was not the case in the multivariate analysis for OS nor for PFS. (4) Conclusion: The established five-gene expression profile in CTCs was not independently associated with PFS nor OS. However, along with alkaline phosphatase and hemoglobin, CTC-count is independently associated with PFS and OS in mCRPC patients who are treated with cabazitaxel.

12.
J Immunother Cancer ; 7(1): 192, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324223

RESUMO

BACKGROUND: Nivolumab is administered in a weight-based or fixed-flat dosing regimen. For patients with non-small cell lung cancer (NSCLC), a potential exposure-response relationship has recently been reported and may argue against the current dosing strategies. The primary objectives were to determine nivolumab pharmacokinetics (PK) and to assess the relationship between drug clearance and clinical outcome in NSCLC, melanoma, and renal cell cancer (RCC). METHODS: In this prospective observational cohort study, individual estimates of nivolumab clearance and the impact of baseline covariates were determined using a population-PK model. Clearance was related to best overall response (RECISTv1.1), and stratified by tumor type. RESULTS: Two-hundred-twenty-one patients with metastatic cancer receiving nivolumab-monotherapy were included of whom 1,715 plasma samples were analyzed. Three baseline parameters had a significant effect on drug clearance and were internally validated in the population-PK model: gender, BSA, and serum albumin. Women had 22% lower clearance compared to men, while the threshold of BSA and albumin that led to > 20% increase of clearance was > 2.2m2 and < 37.5 g/L, respectively. For NSCLC, drug clearance was 42% higher in patients with progressive disease (mean: 0.24; 95% CI: 0.22-0.27 L/day) compared to patients with partial/complete response (mean: 0.17; 95% CI: 0.15-0.19 L/day). A similar trend was observed in RCC, however, no clearance-response relationship was observed in melanoma. CONCLUSIONS: Based on the first real-world population-PK model of nivolumab, covariate analysis revealed a significant effect of gender, BSA, and albumin on nivolumab clearance. A clearance-response relationship was observed in NSCLC, with a non-significant trend in RCC, but not in melanoma. Individual pharmacology of nivolumab in NSCLC appears important and should be prospectively studied.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Idoso , Superfície Corporal , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Renais/metabolismo , Feminino , Humanos , Neoplasias Renais/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Melanoma/metabolismo , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/farmacocinética , Estudos Prospectivos , Albumina Sérica Humana/metabolismo , Fatores Sexuais , Resultado do Tratamento
13.
Oncotarget ; 8(63): 106468-106474, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29290963

RESUMO

BACKGROUND: Treatment selection for men with metastatic castration-resistant prostate cancer (mCRPC) has become increasingly challenging with the introduction of novel therapies at earlier disease stages. The purpose of this study was to identify prognostic factors for overall survival (OS) and PSA response in patients with mCRPC treated with cabazitaxel. RESULTS: 224 mCRPC patients were included in the current analysis. In multivariable analysis, WHO performance status, baseline hemoglobin, alkaline phosphatase and albumin were all significantly associated with OS. Hemoglobin and alkaline phosphatase were significantly associated with PSA response. CONCLUSIONS: This study identified prognostic factors for OS and PSA response of men with mCRPC treated with cabazitaxel. In an increasingly complicated treatment landscape with several treatment options available our findings might serve to estimate the chance of survival of men qualifying for treatment with second-line chemotherapy in daily practice. Furthermore, these data can be used to risk-stratify patients in clinical trials. METHODS: We performed a post-hoc analysis of a randomized phase II trial of mCRPC patients treated with cabazitaxel. Cox and logistic regression models were used to investigate the influence of clinical and biochemical variables on OS and PSA response. Nomograms were developed to estimate the chance of PSA response and OS.

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