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BACKGROUND: Platinum-based chemotherapy (ChT) has been the standard first-line treatment for metastatic urothelial carcinoma (mUC). The purpose of this study was to evaluate the use of induction avelumab followed by avelumab in combination with carboplatin-gemcitabine (carbo/gem) followed by avelumab maintenance. We tested the hypothesis that induction immunotherapy (IO) could enhance the response to ChT and prevent its detrimental effect on immune cells. MATERIALS AND METHODS: INDUCOMAIN is a multicenter, randomized, investigator-initiated, open-label phase II study evaluating the safety and efficacy of induction avelumab before carboplatin-gemcitabine-avelumab, followed by avelumab maintenance (arm A), compared to carbo/gem (arm B). Eligibility criteria included patients with mUC, no prior systemic therapy, and ineligibility for cisplatin by Galsky criteria. Patients were stratified by the presence/absence of visceral metastasis and Eastern Cooperative Oncology Group performance status 0-1 versus 2. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Eighty-five patients were included and randomized to arm A (n = 42) and arm B (n = 43), respectively. ORR was similar between treatment arms: 59.5% in arm A and 53.5% in arm B (P = 0.57). Fourteen patients (33%) in arm A early progressed/died before or at first response assessment, compared to three patients (7%) in arm B. Median OS was 11.1 months in arm A and 13.2 months in arm B [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.57-1.46, P = 0.69]. Median PFS was 6.9 months in arm A versus 7.4 months in arm B (HR 0.99, 95% CI 0.61-1.60, P = 0.95). Treatment-related adverse events of grade 3-4 occurred in 70.7% of patients in arm A and in 72.1% in arm B. No predictive role of programmed death-ligand 1 expression was found. CONCLUSIONS: The hypothesis that induction avelumab could enhance the efficacy of subsequent ChT was not proven. Administering IO alone as induction before ChT is not an adequate strategy.
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Although rejected by the World Health Organization, the human and even veterinary formulation of ivermectin has widely been used for prevention and treatment of COVID-19. In this work we leverage Twitter to understand the reasons for the drug use from ivermectin supporters, their source of information, their emotions, their gender demographics, and location information, in Nigeria and South Africa. Topic modelling is performed on a Twitter dataset gathered using keywords 'ivermectin' and 'ivm'. A model is fine-tuned on RoBERTa to find the stance of the tweets. Statistical analysis is performed to compare the stance and emotions. Most ivermectin supporters either redistribute conspiracy theories posted by influencers, or refer to flawed studies confirming ivermectin efficacy in vitro. Three emotions have the highest intensity, optimism, joy and disgust. The number of anti-ivermectin tweets has a significant positive correlation with vaccination rate. All the provinces in South Africa and most of the provinces of Nigeria are pro-ivermectin and have higher disgust polarity. This work makes the effort to understand public discussions regarding ivermectin during the COVID-19 pandemic to help policy-makers understand the rationale behind its popularity, and inform more targeted policies to discourage self-administration of ivermectin. Moreover, it is a lesson to future outbreaks.
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COVID-19 , Uso Off-Label , Humanos , Nigéria/epidemiologia , África do Sul/epidemiologia , Análise de Sentimentos , Pandemias , COVID-19/epidemiologia , Ivermectina/uso terapêuticoRESUMO
BACKGROUND: The most frequent non-immediate reactions described with iodinated contrast media (ICM) are mild to moderate, however, some cases of patients with severe non-immediate reactions, such as drug eruption with eosinophilia and systemic symptoms (DRESS) have been described. CASE PRESENTATION: An 84-year-old patient developed DRESS syndrome after administration of ICM ioversol. The patient fullfilled the RegiSCAR diagnostic criteria for DRESS (definite score = 6). He underwent intradermal skin testing (IDT) with the widest panel of ICM available at our center. IDT was positive with ioversol and iomeprol. A punch biopsy was performed on the positive IDT with the culprit drug (ioversol) and histopathology was compatible with a T-cell mediated mechanism. CONCLUSION: In this case, the IDT-positive biopsy was consistent with DRESS syndrome caused by T-lymphocyte activation, supporting the clinical diagnosis.
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BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Estudos Prospectivos , Sunitinibe/efeitos adversosAssuntos
Acetato de Abiraterona/uso terapêutico , Alérgenos/efeitos adversos , Antineoplásicos/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Acetato de Abiraterona/efeitos adversos , Administração Oral , Antineoplásicos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Exantema , Humanos , Hipersensibilidade Tardia , Imunização , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Náusea , Neoplasias da Próstata/complicações , VômitoRESUMO
BACKGROUND: Incidence of a second testicular tumor is higher in patients diagnosed with testicular cancer than in the general population. As incidence of unilateral germ cell cancer is increasing worldwide and most of these patients are cured, a growing number of patients at risk of developing a contralateral testis cancer is expected. OBJECTIVE: To analyze clinical and histological characteristics, as well as the absolute and cumulative incidence of a second testicular cancer in a cohort of 3,834 patients diagnosed with germ cell testicular cancer between I/1994 and I/2018 in 18 referral hospitals of the Spanish Germ Cell Cancer Group. METHODS: Patients were treated according to stage and year of diagnoses. Contralateral testis biopsy was not routinely performed, according to European Association of Urology rules. Follow-up of the contra lateral testis consists of a physical exam only and an annual optional testicular ultrasound for 10 years. RESULTS: Median age of the patients included was 32 years (18-82). With a median follow-up of 61 months (0-240), 67/3,834 patients (1.74%) were diagnosed with a second testicular tumor. The second testicular tumor was synchronic (diagnosed within 6 months of the first orchiectomy) in 19 patients, and metachronous in 48. Pathology of the second tumor was reported as a seminomatous testis tumor in 47 patients and a nonseminomatous cancer in 20. Cumulative incidence of contralateral testicular cancer was 2% at 5 years, and 4% (IC 95% 3%-5%) at 14 years. Younger age was a risk factor for developing a second testicular tumor (P = 0.006), whereas chemotherapy reduced the risk for a metachronous testicular cancer (Pâ¯=â¯0.046). Within our cohort, 6 families with testicular cancer aggregation (more than 2 tumors in the same family) were identified. CONCLUSIONS: Incidence of second testicular neoplasm in this cohort of 3,834 patients was similar to that which has been reported in other countries. Metachronous tumors and seminomas are more common. Follow-up of the contralateral testis is mandatory, as well as adequate information for patients to prevent a second neoplasm if feasible, and to detect and treat it as soon as possible.
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Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To assess the diagnostic capability of PET/CT with [18F]F-Fluoromethylcholine in prostate cancer (PC) with biochemical recurrence and its therapeutic impact. MATERIAL AND METHODS: We included 108 patients, diagnosed with PC with biochemical criteria for recurrence. A PET/CT Choline scan was performed by dynamic pelvic and whole body study at 60min post-tracer injection. The relationship between the positive studies and the PSA value was analysed by classifying patients into three groups (<1.2/1.2-2/>2ng/ml), and the diagnostic capacity was assessed with respect to pelvic MRI and the impact on the therapeutic decision. RESULTS: The location of recurrence was identified in 85 of 108 patients (78.7%): 34 local, 47 pelvic lymph nodes and 58 distant lesions, including retroperitoneal, mediastinal lymph nodes and distant organ lesions (bone and lung). Second tumors were diagnosed in 4 patients. No significant differences were found in the percentage of positive studies depending on primary treatment. Patients with PSA>2ng/ml showed a higher percentage of disease detection than patients with a lower PSA level, with significant differences (p<0.0001). PET/CT [18F]F-Choline was able to detect local disease, not previously known from MRI, in 29.41% of patients. PET/CT Choline had an impact on therapeutic management in 67 of 108 patients (62%). CONCLUSIONS: PET/CT with [18F]F-Fluoromethylcholine is a useful tool in the detection of locoregional and disseminated disease of PC treated with suspicion of recurrence, providing a change in therapeutic management in 62% of patients.
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Adenocarcinoma/secundário , Neoplasias Ósseas/secundário , Colina/análogos & derivados , Radioisótopos de Flúor , Calicreínas/sangue , Neoplasias Pulmonares/secundário , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico por imagem , Gerenciamento Clínico , Humanos , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico por imagem , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapia , Sensibilidade e EspecificidadeAssuntos
Pustulose Exantematosa Aguda Generalizada/diagnóstico , Antibacterianos/efeitos adversos , Artroplastia do Joelho , Hipersensibilidade a Drogas/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Pele/patologia , Teicoplanina/efeitos adversos , Pustulose Exantematosa Aguda Generalizada/etiologia , Alérgenos/imunologia , Antibacterianos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Testes do Emplastro , Teicoplanina/imunologia , Teicoplanina/uso terapêuticoRESUMO
BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.
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Anestésicos Gerais/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Atracúrio/efeitos adversos , Atracúrio/análogos & derivados , Feminino , Fentanila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueadores Neuromusculares/efeitos adversos , Período Perioperatório , Valor Preditivo dos Testes , Propofol/efeitos adversos , Remifentanil/efeitos adversos , Rocurônio/efeitos adversos , Testes Cutâneos , Sugammadex/efeitos adversos , Adulto JovemRESUMO
Background: We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer types. Patients and methods: RNASeqv2 data from 10 078 tumor samples representing 34 different cancer types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated. To translate the in silico findings to the clinical setting, we analyzed the expression of PD1 mRNA using the nCounter platform in 773 formalin-fixed paraffin embedded (FFPE) tumor samples across 17 cancer types. To test the direct relationship between PD1 mRNA, PDL1 immunohistochemistry (IHC), stromal tumor-infiltrating lymphocytes (sTILs) and ORR, we evaluated an independent FFPE-based dataset of 117 patients with advanced disease treated with anti-PD1 monotherapy. Results: In pan-cancer TCGA, PD1 mRNA expression was found strongly correlated (r > 0.80) with CD8 T-cell genes and signatures and the proportion of PD1 mRNA-high tumors (80th percentile) within a given cancer type was variable (0%-84%). Strikingly, the PD1-high proportions across cancer types were found strongly correlated (r = 0.91) with the ORR following anti-PD1 monotherapy reported in the literature. Lower correlations were found with other immune-related genes/signatures, including PDL1. Using the same population-based cutoff (80th percentile), similar proportions of PD1-high disease in a given cancer type were identified in our in-house 773 tumor dataset as compared with TCGA. Finally, the pre-established PD1 mRNA FFPE-based cutoff was found significantly associated with anti-PD1 response in 117 patients with advanced disease (PD1-high 51.5%, PD1-intermediate 26.6% and PD1-low 15.0%; odds ratio between PD1-high and PD1-intermediate/low = 8.31; P < 0.001). In this same dataset, PDL1 tumor expression by IHC or percentage of sTILs was not found associated with response. Conclusions: Our study provides a clinically applicable assay that links PD1 mRNA abundance, activated CD8 T-cells and anti-PD1 efficacy.
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Antineoplásicos Imunológicos/uso terapêutico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Neoplasias/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , RNA Mensageiro/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , RNA Mensageiro/genética , Taxa de SobrevidaRESUMO
Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues. Renal toxicity has been described in several ICI but not with atezolizumab, an IgG1 monoclonal antibody targeting PD-L1 (programmed death ligand 1), approved by FDA as a second-line therapy for advanced urothelial carcinoma. Here we present a patient with a single kidney and metastatic renal cell carcinoma treated with atezolizumab and bevacizumab combination, with biopsy-proven acute interstitial nephritis, who had a complete resolution of renal dysfunction after steroid therapy.
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The original article shows two mistakes, which are listed here.
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Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma.
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Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Humanos , MasculinoRESUMO
BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).
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Androstenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenos/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Benzamidas , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Análise Mutacional de DNA , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Análise Multivariada , Mutação , Nitrilas , Razão de Chances , Seleção de Pacientes , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Medicina de Precisão , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/mortalidade , Receptores Androgênicos/genética , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed.
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Neoplasias Urogenitais/terapia , HumanosRESUMO
Androgen deprivation treatment is the current standard first-line treatment for metastatic prostate cancer. For several years, docetaxel was the only treatment with a proven survival benefit for castration-resistant prostate cancer (CRPC). Since docetaxel became standard of care for men with symptomatic metastatic castration-resistant prostate cancer (CRPC), three treatment virtual spaces, for treatment and drug development in CPRC, have emerged: pre-docetaxel, docetaxel combinations and post-docetaxel. Sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 have been approved in the pre- or post-docetaxel setting in metastatic CRPC during the last few years. Patients are now living longer and experiencing better quality of life. Strategies for patient selection and treatment sequencing are therefore urgently required.
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Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Humanos , MasculinoRESUMO
BACKGROUND: Biomarkers for metastatic castration-resistant prostatic cancer (mCRPC) are an unmet medical need. METHODS: The prognostic and predictive value for survival and response to salvage hormonal therapy (SHT) of baseline testosterone level (TL) was analysed in a cohort of 101 mCRPC patients participating in 9 non-hormonal first-line chemotherapy phase II-III trials. Inclusion criteria in all trials required a TL of <50 ng dl(-1). RESULTS: Median age: 70 years; visceral metastases: 19.8%; median prostate-specific antigen (PSA): 50.7 ng ml(-1); median TL: 11.5 ng dl(-1). Median overall survival (OS; 24.5 months) was significantly longer if baseline TL was above (High TL; n=52) than under (Low TL; n=49) the TL median value (32.7 vs 22.4 months, respectively; P=0.0162, hazard ratio (HR)=0.6). The presence of anaemia was an unfavourable prognostic factor (median OS: 20.6 vs 28.4 months; P=0.0025, HR=1.88 (CI95%: 1.01-3.48)). Patients presenting both anaemia and low testosterone had a worse outcome compared to those with one or none of them (median OS: 17.9 vs 22.4 vs 38.1 months; P=0.0024). High vs Low TL was associated with PSA response rate (55.6% vs 21.7%) in 41 patients receiving SHT. CONCLUSION: Testosterone level under castration range was a prognostic factor for survival mCRPC patients. The PSA response to SHT differed depending on TLs. Testosterone levels might help in treatment decision.