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BACKGROUND/AIM: The therapeutic impact of combination treatment with an immune checkpoint inhibitor (ICI) and chemotherapeutic agent on patients with urothelial cancer (UC) remains controversial. Therefore, the present study investigated differences in the therapeutic effects of combination therapy with cisplatin plus anti-mouse programmed death (PD)-1 antibody according to the dose of cisplatin using the mouse bladder tumor model MBT2. MATERIALS AND METHODS: The effects of treatment with two different doses cisplatin and/or anti-mouse PD-1 antibody on tumor growth after the subcutaneous injection of MBT2 cells were compared. Infiltrating patterns of lymphocytes into tumors after treatment were assessed using immunohistochemical staining. RESULTS: MBT2 tumor volumes were significantly larger in mice receiving high-dose cisplatin alone than in those receiving low-dose cisplatin alone. Combination treatment with cisplatin plus anti-mouse PD-1 antibody exerted significantly stronger growth inhibitory effects on MBT2 tumors than treatment with either agent alone, irrespective of cisplatin doses; however, no significant differences were observed in MBT2 tumor volumes between mice receiving anti-mouse PD-1 antibody plus high-dose cisplatin and those receiving anti-mouse PD-1 antibody plus low-dose cisplatin. Furthermore, CD8+ to CD3+ and CD8+ to CD11b+ T-lymphocyte ratios in MBT2 tumors were both significantly higher in the low-dose cisplatin alone group than in the high-dose cisplatin alone group, whereas no significant differences were noted in either ratio between the two different combination treatment regimens. CONCLUSION: When combined with ICI, a lower dose of cisplatin may achieve favorable antitumor effects in UC patients by preventing lymphocyte exhaustion.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Animais , Camundongos , Cisplatino , Receptor de Morte Celular Programada 1 , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Linfócitos T/patologiaRESUMO
Vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors (VEGFR-TKIs) are often used for treatment of several types of cancer; however, they are associated with an increased risk of proteinuria, sometimes leading to treatment discontinuation. We searched PubMed and Scopus to identify clinical studies examining the incidence and risk factors for proteinuria caused by VEGFR-TKIs in patients with renal cell carcinoma, thyroid cancer, and hepatocellular carcinoma. The global incidence of proteinuria ranged from 6% to 34% for all grades of proteinuria, and from 1% to 10% for grade ≥3 proteinuria. The incidence of proteinuria did not differ significantly by cancer type, but in all three cancer types, there was a trend toward a higher incidence of proteinuria with lenvatinib than with other VEGFR-TKIs. In terms of risk factors, the incidence of proteinuria was significantly higher among Asians (including Japanese) compared with non-Asian populations. Other risk factors included diabetes mellitus, hypertension, and previous nephrectomy. When grade 3/4 proteinuria occurs, patients should be treated according to the criteria for dose reduction or withdrawal specified for each drug. For grade 2 proteinuria, treatment should be continued when the benefits outweigh the risks. Referral to a nephrologist should be considered for symptoms related to decreased renal function or when proteinuria has not improved after medication withdrawal. These management practices should be implemented universally, regardless of the cancer type.
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Carcinoma Hepatocelular , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Hepáticas , Proteinúria , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/complicações , Incidência , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Prevalência , Proteinúria/epidemiologia , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fatores de Risco , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/epidemiologia , /uso terapêuticoRESUMO
BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a serious adverse event potentially induced by any antineoplastic agent. Whether cancer patients are predisposed to a higher risk of DIILD after receiving immune checkpoint inhibitors (ICIs) is unknown. METHODS: This study retrospectively assessed the cumulative incidence of DIILD in consecutive cancer patients who received post-ICI antineoplastic treatment within 6 months from the final dose of ICIs. There was also a separate control cohort of 55 ICI-naïve patients with non-small cell lung cancer (NSCLC) who received docetaxel. RESULTS: Of 552 patients who received ICIs, 186 met the inclusion criteria. The cohort predominantly comprised patients with cancer of the lung, kidney/urinary tract, or gastrointestinal tract. The cumulative incidence of DIILD in the entire cohort at 3 and 6 months was 4.9% (95% confidence interval [CI] 2.4%-8.7%) and 7.2% (95% CI 4.0%-11.5%), respectively. There were significant differences according to cancer type (Gray's test, P = .04), with the highest cumulative incidence of DIILD in patients with lung cancer being 9.8% (95% CI 4.3%-18.0%) at 3 months and 14.2% (95% CI 7.3%-23.3%) at 6 months. DIILD was caused by docetaxel in six of these 11 lung cancer patients (54.5%). After matching, the cumulative incidence of docetaxel-induced ILD in patients with NSCLC in the post-ICI setting was higher than that in the ICI-naïve setting: 13.0% (95% CI 3.3%-29.7%) vs 4.3% (95% CI 0.3%-18.2%) at 3 months; and 21.7% (95% CI 7.9%-39.9%) vs 4.3% (95% CI 0.3%-18.2%) at 6 months. However, these were not significant differences (hazard ratio, 5.37; 95% CI 0.64-45.33; Fine-Gray P = .12). CONCLUSIONS: Patients with lung cancer were at high risk of developing DIILD in subsequent regimens after ICI treatment. Whether NSCLC patients are predisposed to additional risk of docetaxel-induced ILD by prior ICIs warrants further study.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Docetaxel/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologiaRESUMO
BACKGROUND: Among patients with non-muscle-invasive bladder cancer (NMIBC), systematic reviews showed lower recurrence rate in patients treated with photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) than with white-light (WL) TURBT. However, the result is not consistent between clinical trials and the significance of preoperatively available factors in disease recurrence after PDD-TURBT remains unclear. METHODS: The present study retrospectively analyzed 1174 NMIBC patients who underwent TURBT and were followed up for ≥ 6 months. Among 1174 patients, 385 and 789 underwent PDD-TURBT with oral 5-aminolevulinic acid (the PDD group) and WL-TURBT (the WL group), respectively. Recurrence-free survival (RFS) was compared between the PDD and WL groups before and after propensity score matching, and the impact of several baseline parameters on RFS between the 2 groups was investigated after matching. RESULTS: Before propensity score matching, RFS was significantly longer in the PDD group than in the WL group (P = 0.006). After matching, 383 patients were included in both groups, and RFS was significantly longer in the PDD group than in the WL group (P < 0.001). In the cohort after matching, RFS between the two groups was compared in each subgroup classified according to baseline parameters, including age, sex, history of previous or concomitant upper urinary tract urothelial carcinoma, preoperative urinary cytology, tumor multiplicity, and tumor size, and significantly longer RFS was observed in the PDD group in all subgroups, except for the patients with tumors ≥ 30 mm (P = 0.21). CONCLUSION: These results suggest that PDD-TURBT prolongs RFS in NMIBC patients, except for those with tumors ≥ 30 mm.
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Carcinoma de Células de Transição , Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Ácido Aminolevulínico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Cistectomia/métodos , Recidiva Local de Neoplasia/patologia , Invasividade NeoplásicaRESUMO
OBJECTIVES: Bladder cancer, especially non-muscle invasive bladder cancer (NMIBC), is one of the most costly cancers owing to its long-term management. Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) reduces the risk of intravesical recurrence. However, its impact on healthcare economics in Japan remains unclear. We evaluated the comprehensive medical costs of Japanese healthcare economics regarding PDD-TURBT. METHODS: This large-scale, multicenter, retrospective study included a dataset of 1531 patients who were diagnosed with primary NMIBC who underwent initial TURBT between April 2006 and June 2021. A one-to-one propensity-score matching analysis was used for an unbiased comparison based on postTURBT follow-up periods. The total medical costs, including hospitalization, surgical procedures for TURBT and salvage radical cystectomy, adjuvant intravesical therapies, and follow-up examinations, were compared between white light (WL)-TURBT and PDD-TURBT groups. RESULTS: After propensity-score matching, 468 patients each of WL- and PDD-TURBT groups were matched. Total costs were 510 337 128 and 514 659 328 ¥ in WL- and PDD-TURBT groups, respectively. The costs of adjuvant intravesical therapies, follow-up examinations, and salvage radical cystectomy in PDD-TURBT group were equivalent to or lower than those in WL-TURBT group. Furthermore, total costs of high- and highest-risk NMIBC in PDD-TURBT group were either equivalent or lower compared to those in WL-TURBT group. CONCLUSIONS: The total costs associated with PDD-TURBT were higher compared to WL-TURBT, while there is the potential of PDD-TURBT to reduce the burden on healthcare economics in limited cases.
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Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/métodos , Atenção à Saúde , População do Leste Asiático , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Fármacos Fotossensibilizantes , Estudos Retrospectivos , Ressecção Transuretral de Bexiga , Neoplasias da Bexiga Urinária/patologia , FotoquimioterapiaAssuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Ipilimumab/uso terapêutico , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/etiologia , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Introduction: Innovation of robotic surgery is still actively growing, and various novel robotic systems are in the process of development. The objective of this study was to assess the perioperative outcomes of robot-assisted partial nephrectomy (RAPN) using the hinotori surgical robot system, a recently developed robot-assisted surgical platform, for patients with small renal tumors. Methods: This study prospectively included a total of 30 consecutive patients who were found to have small renal tumors and subsequently underwent RAPN using hinotori between April and November 2022. Major perioperative outcomes in these 30 patients were comprehensively analyzed. Results: The median tumor size and R.E.N.A.L. nephrometry score in the 30 patients were 28 and 8 mm, respectively. Of these 30, 25 and 5 received RAPN by intra- and retroperitoneal approaches, respectively. RAPN could be completed in all 30 patients without conversion to nephrectomy or open surgery. The median operative time, time using hinotori, and warm ischemia time were 179, 106, and 13 minutes, respectively. No patient was found to have a positive surgical margin or experienced major perioperative complications, corresponding to Clavien-Dindo 3≤. Achievements of trifecta and margin, ischemia, and complications (MIC) outcomes in this series were 100% and 96.7%, respectively, and median changes in the estimated glomerular filtration rate 1 day and 1 month after RAPN were -20.9% and -11.7%, respectively. Conclusions: This is the first study focusing on RAPN using hinotori, which showed favorable perioperative outcomes, considering the findings of trifecta and MIC. Although it will be necessary to investigate the long-term effects of RAPN using hinotori on oncologic and functional outcomes, the present findings strongly suggest that the hinotori surgical robot system could be safely applied to RAPN for patients with small renal tumors.
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Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Estudos Retrospectivos , Nefrectomia/efeitos adversos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologiaRESUMO
The aim of the present study was to evaluate the prognosis of Japanese patients with metastatic renal cell carcinoma (mRCC) receiving nivolumab and to identify factors predicting the overall survival (OS) in this cohort of patients. This study retrospectively assessed the outcomes of 77 consecutive Japanese patients with mRCC who were treated using either 1 or 2 molecular-targeted agents followed by nivolumab in routine clinical practice. The best responses to nivolumab observed were as follows: Complete response in 3 patients, partial response in 27, stable disease in 33 and progressive disease in 14; therefore, the objective response rate in the 77 patients was 39.0%. During the median follow-up period of 11 months after the introduction of nivolumab, the median progression-free survival and OS were 7 months and not reached, respectively. On multivariate analysis of several parameters, age, Karnofsky Performance Status (KPS) and neutrophil counts were demonstrated to be independently associated with OS in the 77 patients. By dividing these patients into 3 groups according to 3 risk factors, it was possible to stratify the OS; however, the International Metastatic Renal Cell Carcinoma Database Consortium model was unable to classify the OS. These results suggested that age, KPS and neutrophil counts were useful predictors of OS in previously treated patients with mRCC who received nivolumab.
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BACKGROUND/AIM: The objective of this study was to investigate the significance of the blood levels of free amino acids (AAs) in infertile men. PATIENTS AND METHODS: Ninety-three men who underwent examinations for infertility were included. The concentrations of 20 AAs were measured and compared in four groups (normospermia, obstructive azoospermia, oligozoospermia, non-obstructive azoospermia) based on semen analysis and clinical parameters. RESULTS: When the 93 men were divided into normospermia, obstructive azoospermia, oligozoospermia, and non-obstructive azoospermia groups, no significant differences were found in the concentrations of the 20 AAs between them. We then compared 49 men diagnosed with normozoospermia or oligozoospermia according to the median sperm motility and morphology abnormalities rates (30% and 20%, respectively). Men with low motility rates had significantly lower levels of tryptophan and alanine, and men with high abnormal morphology rates had significantly lower levels of aspartate and glutamate. CONCLUSION: AAs are probably involved in the pathogenesis of male infertility, particularly oligozoospermia.
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Azoospermia , Infertilidade Masculina , Oligospermia , Aminoácidos , Azoospermia/diagnóstico , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Oligospermia/diagnóstico , Motilidade dos EspermatozoidesRESUMO
BACKGROUND/AIM: There are limited data on comprehensive assessments of several treatments as second-line therapy against advanced urothelial cancer (UC). The objective of this study was to compare clinical outcomes between advanced UC patients receiving either pembrolizumab (Pem) or combined chemotherapy with gemcitabine and paclitaxel (GP) as second-line therapy. PATIENTS AND METHODS: This study retrospectively analyzed the clinical outcomes of 89 patients with platinum-refractory advanced UC, consisting of 46 and 43 who received Pem and GP therapy, respectively, as second-line treatment. RESULTS: There were no significant differences in major clinicopathological parameters between Pem and GP groups. No significant difference in the objective response rate was noted between the two groups. Progression-free survival (PFS) in the Pem group was significantly longer than that in the GP group; however, there was no significant difference in overall survival (OS) between them. Multivariate analyses identified performance status ≤2 and liver metastasis as independent factors associated with poor outcomes in both PFS and OS. The incidence of adverse events in the GP group was significantly higher than that in the Pem group. CONCLUSION: Pem could be regarded as standard agent for platinum-refractory advanced UC patients.
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Carcinoma de Células de Transição , Platina , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Desoxicitidina/análogos & derivados , Humanos , Paclitaxel/efeitos adversos , Estudos Retrospectivos , GencitabinaRESUMO
The aims of the current study were to analyze the oncological outcomes of patients with high-risk non-invasive bladder cancer (NMIBC) and to identify prognostic factors in these patients. The present study included 186 consecutive patients who underwent transurethral resection of the bladder tumor (TURBT) between January 2007 and June 2017 at Hamamatsu University School of Medicine and were subsequently diagnosed with high-risk NMIBC according to the classification of the European Urological Association guidelines. The oncological outcomes, including recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in the 186 patients were evaluated. Additionally, the effects of several clinicopathologiocal parameters on these outcomes were investigated. After the initial TURBT, the second transurethral resection and intravesical bacillus of Calmette-Guerin (BCG) therapy were performed for 47 (25.3%) and 108 (58.1%) patients, respectively. During the observation period of the current study, disease recurrence, disease progression and overall deaths occurred in 54 (29.0%), 14 (7.5%) and 19 (10.2%) patients, respectively. The 5-year RFS, PFS and OS rates in the 186 patients were 66.6, 90.2 and 87.2%, respectively. Multivariate analyses using the Cox proportional hazards regression model identified the following independent factors for the oncological outcomes: Tumor multiplicity and introduction of BCG therapy for RFS (P=0.018 and P<0.008, respectively), tumor multiplicity and recurrence status for PFS (P=0.043 and P=0.029, respectively), and age and tumor multiplicity for OS (P<0.008 and P=0.041, respectively). Although management following initial TURBT was insufficient, the oncological outcomes in the present series were comparable to those in previous studies targeting high-risk patients with NMIBC. However, attention should be paid to patients with factors independently associated with poor prognostic outcomes, particularly those with multiple tumors.
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BACKGROUND/AIM: Despite recent introduction of several novel agents, limited data exist regarding parameters that help predict the progression of non-metastatic castration-resistant prostate cancer (nmCRPC). The objective of this study was to identify prognostic predictors in nmCRPC patients. PATIENTS AND METHODS: This study included 127 consecutive Japanese nmCRPC patients treated in routine clinical practice. Prognostic outcomes in these patients were analyzed to evaluate the impact of several parameters on prostate-specific antigen progression-free survival (PSA PFS) and metastasis-free survival (MFS). RESULTS: When the 127 patients were diagnosed with nmCRPC, the PSA and PSA doubling time (PSADT) were 13.5 ng/ml and 17.9 months, respectively. Of these, 77 (60.6%) and 50 (39.4%) were treated with first-generation anti-androgen (FGA) and novel androgen-receptor-axis-targeted agent (ARATA), respectively, as first-line therapy for nmCRPC. The median PSA PFS and MFS after the diagnosis of nmCRPC in these patients were 29.5 months and not reached, respectively. Multivariate analyses identified the following independent prognostic factors: PSA at nmCRPC, PSADT and first-line therapy for nmCRPC for PSA PFS, and PSA at nmCRPC and PSADT for MFS. CONCLUSION: nmCRPC patients with higher PSA and/or shorter PSADT should be treated with ARATA rather than FGA.
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Neoplasias de Próstata Resistentes à Castração/diagnóstico , Biomarcadores Tumorais , Terapia Combinada , Progressão da Doença , Humanos , Japão , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias de Próstata Resistentes à Castração/etiologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/terapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: The objective of this study was to evaluate our experience with robot-assisted partial nephrectomy (RAPN) in comparison with conventional open partial nephrectomy (OPN). PATIENTS AND METHODS: This study included 37 and 50 patients undergoing OPN and RAPN for small renal masses, respectively. A single surgeon performed RAPN for all 50 cases using the da Vinci Xi. Trifecta was defined as satisfying all of the following 3 criteria: ischemic time of ≤ 25 minutes, negative surgical margin and no major postoperative complications. RESULTS: After adjusting patient variables by 1:1 propensity-score matching, 37 patients were included in each group, and no significant differences in major clinicopathological characteristics were noted between these 2 groups. RAPN was significantly superior to OPN with respect to operative time, estimated blood loss and postoperative length of hospital stay. The rate of trifecta achievement was significantly higher in the RAPN group than in the OPN group (91.9 vs. 62.2%). Furthermore, the operative procedure and R.E.N.A.L. nephrometry score were found to be independently associated with trifecta outcome by multivariate analysis of the entire cohort. CONCLUSIONS: Although this is our early experience with 50 initial cases, RAPN using the da Vinci Xi resulted in more favorable perioperative outcomes than OPN.
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BACKGROUND: To compare the prognostic outcomes between first-generation antiandrogen (FGA) and novel androgen-receptor-axis-targeted agent (ARATA) as first-line therapy in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). METHODS: This study retrospectively included a total of 103 consecutive nmCRPC patients consisting of 47 (45.6%) and 56 (54.4%) who received FGA (bicalutamide or flutamide) and ARATA (abiraterone acetate or enzalutamide), respectively, as the first-line agent after the failure of primary androgen deprivation therapy (ADT). RESULTS: There were no significant differences in the major clinicopathological parameters and previous therapeutic histories between the FGA and ARATA groups. During the observation period, 31 (66.0%) and 29 (51.8%) discontinued first-line therapy in the FGA and ARATA groups, respectively, and of these, 27 (87.1%) and 23 (79.3%) in the FGA and ARATA groups, respectively, were subsequently treated with approved agents as second-line therapy. The prostate-specific antigen (PSA) response rate in the FGA group was significantly lower than that in the ARATA group. Although no significant difference in overall survival was noted between the FGA and ARATA groups, there were significant differences in the PSA progression-free survival on first-line therapy and metastasis-free survival between the two groups, favoring the ARATA group compared with FGA group. CONCLUSIONS: Collectively, these findings suggest that among nmCRPC patients who progressed following treatment with the primary ADT, the introduction of ARATA may result in the delay of disease progression compared with FGA.
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Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Terapia de Alvo Molecular/métodos , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/uso terapêutico , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND/AIM: To date, it has not been well characterized whether sunitinib is effective in elderly patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to investigate the impact of age on clinical outcomes of mRCC patients receiving sunitinib. PATIENTS AND METHODS: The efficacy and safety of first-line sunitinib in 154 consecutive mRCC patients were retrospectively compared between patients aged <75 (n=125) and ≥75 (n=29) years. RESULTS: There were no significant differences in the major clinicopathological characteristics between younger and older patients; however, the reduction of the initial dose of sunitinib was significantly more frequent in older than younger patients. No significant difference in response rate, clinical benefit rate or proportion of patients going on to receive second-line therapy was noted between these two groups. Furthermore, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two groups, and no significant impact of age on PFS or OS was documented by the Cox proportional hazards regression analyses. Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients. Although there was no significant difference in the incidence of dose reduction or discontinuation of sunitinib between the two groups, the interruption of sunitinib was more frequently required in older than younger patients. CONCLUSION: These findings suggest that advanced age alone should not be regarded as a contraindication to the introduction of sunitinib as first-line systemic therapy for mRCC patients.
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Envelhecimento , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Povo Asiático , Carcinoma de Células Renais/etnologia , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Fadiga/induzido quimicamente , Feminino , Humanos , Indóis/efeitos adversos , Japão , Neoplasias Renais/etnologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pirróis/efeitos adversos , Estudos Retrospectivos , Sunitinibe , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
The objective of this study was to investigate the impact of prior treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), on the activity of subsequently introduced docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 114 mCRPC patients consisting of 54 and 60 who progressed following treatment with AA and Enz, respectively, prior to the introduction of docetaxel, and compared oncological outcomes with docetaxel between these two groups. There were no significant differences in the major clinicopathological characteristics before treatment with docetaxel between the AA and Enz groups. The prostate-specific antigen (PSA) response rates to docetaxel in the AA and Enz groups were 40.7 and 43.3%, respectively, with no significant differences in the rates between these two groups. Following the introduction of docetaxel, the median PSA progression-free survival (PFS) and overall survival (OS) in the 114 patients were 7.2 and 17.5 months, respectively. There was no significant difference in the PSA PFS or OS between the AA and Enz groups. Despite the lack of a significant impact of the type of ARAT agent on PSA PFS or OS by univariate analysis, multivariate analyses identified the following independent prognostic predictors: performance status (PS) for PSA PFS and PS and visceral metastasis for OS. Collectively, these findings suggest that the type of ARAT agent may not have a significant impact on disease control by subsequent docetaxel therapy in mCRPC patients.
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Acetato de Abiraterona/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/metabolismo , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Benzamidas , Intervalo Livre de Doença , Docetaxel , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively. RESULTS: Of these patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the 2 groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (21.3%) was significantly lower than that of the first-line ARAT agent (58.3%). The combined PSA PFS in the AA-to-Enz group (median, 18.4 months) was significantly superior to that of the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (ie, AA-to-Enz vs. Enz-to-AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients. However, there was no significant difference in overall survival (OS) between the 2 groups. CONCLUSIONS: Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naïve patients with mCRPC, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series with respect to combined PSA PFS but not OS.
Assuntos
Acetato de Abiraterona/uso terapêutico , Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Humanos , Calicreínas , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Nitrilas , Feniltioidantoína/uso terapêutico , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores Androgênicos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To comprehensively analyze the efficacy of axitinib for metastatic renal-cell carcinoma (mRCC) patients. PATIENTS AND METHODS: This study included 124 consecutive Japanese patients treated with axitinib as second-line systemic therapy for mRCC in a routine clinical setting. RESULTS: In addition to 4 indeterminate patients (3.2%), 0 (0%), 21 (16.9%), 87 (70.2%), and 12 (9.7%) were judged to show complete response, partial response, stable disease, and progressive disease, respectively, as the best responses to axitinib. The median progression-free survival (PFS) and overall survival (OS) after initiating treatment with axitinib were 9.3 and 27.0 months, respectively. Multivariate analyses of several parameters identified the following independent predictors of PFS and OS: Memorial Sloan Kettering Cancer Center (MSKCC) classification and C-reactive protein level for PFS; and MSKCC classification, C-reactive protein level, bone metastasis, and liver metastasis for OS. Common grade 3 or higher adverse events associated with axitinib were hypertension in 41 (33.1%), proteinuria in 14 (11.3%), and hand-foot syndrome in 14 (11.3%). Quality-of-life analysis using the Medical Outcomes Study 36-Item Short Form showed that 2 scores were significantly improved 12 weeks after the administration of axitinib, while there were no significant differences in the remaining 6 scores between surveys administered before and 12 weeks after the treatment with axitinib. CONCLUSION: Favorable disease control could be achieved with acceptable tolerability by introducing axitinib as second-line systemic therapy, resulting in improvement of the prognosis and quality of life of Japanese patients with mRCC.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Imidazóis/administração & dosagem , Indazóis/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Carcinoma de Células Renais/psicologia , Intervalo Livre de Doença , Feminino , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Japão , Neoplasias Renais/psicologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida/psicologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The objective of the present study was to comprehensively compare the clinical outcomes between abiraterone acetate (AA) and enzalutamide (Enz) in Japanese patients with docetaxel-naive metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The present study retrospectively included 280 consecutive mCRPC patients, consisting of 113 and 167 who had received AA and Enz, respectively, without previous treatment with docetaxel. RESULTS: Of the several baseline characteristics examined, some parameters, including performance status (PS), prostate-specific antigen (PSA) value, and incidence of lymph node metastasis, significantly favored the Enz over the AA group. The PSA response rate in the Enz group was significantly greater than that in the AA group, and the PSA progression-free survival in the Enz group was significantly superior to that in the AA group. Multivariate analyses of several parameters identified the following independent predictors of PSA progression-free survival: duration of androgen deprivation therapy and PS for the AA group, age and PS for the Enz group, and PS but not the introduced agent (ie, AA vs. Enz) for the overall patients. The common adverse events observed in the present series were fatigue (19.4%) and liver toxicity (11.5%) in the AA group and fatigue (32.3%) and appetite loss (19.2%) in the Enz group. In addition, the proportion of patients with adverse events grade ≥ 3 in the Enz group (11.4%) was significantly greater than that in the AA group (4.4%). CONCLUSION: Both AA and Enz were effective and tolerable for patients with docetaxel-naive mCRPC in the routine clinical setting.
Assuntos
Acetato de Abiraterona/administração & dosagem , Antineoplásicos/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Benzamidas , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
The objective of this study was to characterize changes in the quality of life (QOL) of Japanese patients following robot-assisted radical prostatectomy (RARP). This study included 298 consecutive localized prostate cancer (PC) patients undergoing RARP. The health-related QOL and disease-specific QOL were assessed using The Medical Outcomes Study 8-Item Short Form (SF-8) and The Extended Prostate Cancer Index Composite (EPIC), respectively, before and 1, 3, 6, 12 and 24 months after RARP. At 1 month after RARP, four (physical function, role limitations because of physical health problems, social function and role limitations because of emotional problems) of the eight scores in SF-8 were significantly impaired compared with those of baseline scores. However, all eight scores on all postoperative assessments, except for at 1 month after RARP, showed no significant differences from baseline scores. Although there were no significant differences in the bowel function, bowel bother, sexual bother, hormonal function or hormonal bother between baseline and postoperative assessments of EPIC at all time points, the urinary function, urinary incontinence and sexual function scores at 1, 3 and 6 months after RARP were significantly inferior to those of baseline scores, and urinary bother and urinary irritation/obstruction scores at 1 month after RARP were significantly impaired compared with those of baseline scores. These findings suggest that the health-related QOL of Japanese PC patients undergoing RARP may not be markedly deteriorated following RARP; however, as for the disease-specific QOL, urinary and sexual functions, particularly those early after RARP, appeared to be significantly impaired.