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1.
Arch Esp Urol ; 71(4): 400-408, 2018 May.
Artigo em Espanhol | MEDLINE | ID: mdl-29745929

RESUMO

In an effort to decrease recurrence and progression rates in non-muscle-invasive bladder cancer (NMIBC), transurethral resection of a bladder tumor is followed by intravesical instillations using Mitomycin-C (MMC) and Bacillus Calmette-Guérin (BCG). In spite of these adjuvant treatment modalities, recurrence and progression rates remain high. Because of these limitations of current standard therapy and the shortage of BCG, there is a search for alternative forms of treatment in NMIBC. Intravesical MMC combined with hyperthermia, especially RF-induced QHT being most extensively investigated in the past 20 years, is one of these alternatives for intermediate- and high-risk NMIBC. There are several different techniques and devices to create hyperthermia of the bladder wall raising temperatures up to 40.5-44.0 ℴ C. Hyperthermia can be the result of ultrasound waves, direct thermal conduction, or electromagnetic fields. An overview of hyperthermia systems concerning their technical aspects, treatment outcomes and adverse events (AE's) will be described in this review. In patients failing standard treatment who are not fit or unwilling to undergo surgery, RF-induced QHT should be considered. Besides QHT, there are more forms of treatment currently being investigated in NMIBC like EMDA and neoadjuvant intravesical chemotherapy, these require more clinical trials to determine patient selection and efficiency.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Hipertermia Induzida , Mitomicina/administração & dosagem , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Terapia Combinada , Previsões , Humanos , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/patologia
2.
Int J Hyperthermia ; 34(7): 988-993, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29191126

RESUMO

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a highly recurrent disease with potential progression to muscle invasive disease despite the standard bladder instillations with mitomycin C (MMC) or Bacille Calmette-Guérin immunotherapy. Therefore, alternatives such as radiofrequency-induced chemohyperthermia (RF-CHT) with MMC are being investigated. The mechanism explaining the efficacy of RF-CHT is only partly understood. We examined whether RF-CHT results in higher MMC tissue concentrations as compared to cold MMC instillation. PATIENTS AND METHODS: Prior to a planned transurethral resection of bladder tumour (TURBT), patients with stage Ta NMIBC were allocated to either (1) cold MMC instillation or (2) RF-CHT. After MMC instillation, three biopsies were taken of both normal and tumour tissue. Biopsies were snap-frozen and MMC tissue concentrations were analysed using ultra-performance liquid chromatography. RESULTS: Eleven patients were included of which six received RF-CHT. Ten patients had TaG2-LG/HG papillary tumours at pathology. One patient in the RF-CHT group appeared to be free of malignancy and was excluded from the analysis as no tumour biopsies were available. The median MMC concentration in tumour tissue was higher in the RF-CHT group (median 665.00 ng/g vs. 63.75 ng/g, U = 51.0, p = 0.018). Moreover, in both techniques the MMC concentration was lower in normal tissue compared to tumour tissue. Tissue MMC concentration measurements varied substantially within, and between, different patients from the same group. CONCLUSION: Intravesical RF-CHT results in higher tumour MMC concentrations vs. cold MMC instillation which contributes to its superior efficacy.


Assuntos
Hipertermia Induzida/métodos , Mitomicina/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/farmacologia , Neoplasias da Bexiga Urinária/patologia
3.
Eur Urol ; 69(6): 1046-52, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26803476

RESUMO

BACKGROUND: Despite adjuvant intravesical therapy, recurrences in non-muscle-invasive bladder cancer (NMIBC) are still high; therefore, new treatment options are needed. The use of chemohyperthermia (CHT) as an alternative treatment is expanding in Europe. To date, however, there has been a lack of prospective randomised data. OBJECTIVE: To compare CHT using mitomycin C (MMC) with bacillus Calmette-Guérin (BCG) as adjuvant treatment for intermediate- and high-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 2002 and 2012, 190 NMIBC patients were randomised in this controlled, open-label, multicentre trial for 1-yr CHT (six weekly treatments and six maintenance treatments) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment. This study is registered with ClinicalTrials.gov (NCT00384891). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was 24-mo recurrence-free survival (RFS) in the intention-to-treat (ITT) and per-protocol (PP) analyses in all papillary NMIBC patients (n=147). Analyses were done with the log-rank test and Fisher exact test. All tests were two-sided. RESULTS AND LIMITATIONS: The 24-mo ITT RFS was 78.1% in the CHT group compared with 64.8% in the BCG group (p=0.08). The 24-mo RFS in the PP analysis was 81.8% in the CHT group compared with 64.8% in the BCG group (p=0.02). Progression rates were <2% in both groups. Regarding the side-effects, no new safety concerns were identified. A concern is that this study closed prematurely and thus is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias. CONCLUSIONS: CHT is a safe and effective treatment option in patients with intermediate- and high-risk papillary NMIBC. A significantly higher 24-mo RFS in the CHT group was seen in the PP analysis. Based on the results above, CHT is an option for BCG therapy as adjuvant treatment for intermediate- and high-risk papillary NMIBC. PATIENT SUMMARY: Recurrences in non-muscle-invasive bladder cancer are common, despite adjuvant therapies. We compared 24-mo recurrence-free survival (RFS) with chemohyperthermia (CHT) versus bacillus Calmette-Guérin (BCG) therapy. According to these data, CHT therapy appears to be safe and has higher 24-mo RFS than BCG therapy.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Carcinoma in Situ/terapia , Carcinoma Papilar/terapia , Hipertermia Induzida , Mitomicina/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , Carcinoma in Situ/patologia , Carcinoma Papilar/patologia , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/patologia , Invasividade Neoplásica , Estudos Prospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/patologia
4.
World J Urol ; 33(10): 1411-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25491674

RESUMO

OBJECTIVES: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders. METHODS: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex(®)-analysis. RESULTS: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders. CONCLUSION: MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.


Assuntos
Carcinoma de Células de Transição/terapia , Citocinas/urina , Hipertermia Induzida/métodos , Mitomicina/administração & dosagem , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/patologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Instilação de Medicamentos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
5.
J Urol ; 192(3): 708-13, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24704017

RESUMO

PURPOSE: Nonmuscle invasive bladder cancer is characterized by a high recurrence rate. New adjuvant treatments are needed to decrease this high number of recurrences. We present the results of more than 10 years of experience with chemohyperthermia in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Using standardized medical record forms we prospectively collected patient and tumor characteristics of patients treated with chemohyperthermia between 2002 and 2013. Median followup was 75.6 months. Recurrence-free survival was the primary objective. The secondary objective was to observe recurrence-free survival differences in 1) the epirubicin group vs the mitomycin group and 2) the highly recurrent (greater than 2 recurrences in 24 months) nonmuscle invasive bladder cancer group vs the other groups. RESULTS: A total of 160 patients with nonmuscle invasive bladder cancer were included in study, including 20 (13%) treated with epirubicin and 129 (81%) previously treated with bacillus Calmette-Guérin. One and 2-year recurrence-free survival was 60% and 47%, respectively. Muscle invasive progression was seen in 4% of cases. Two-year recurrence-free survival in the epirubicin and mitomycin groups was 55% and 46%, respectively (p = 0.30). The highly recurrent nonmuscle invasive bladder cancer group had significant decreased recurrence-free survival compared to other groups (p <0.01). Patients treated with 2 or fewer vs greater than 2 transurethral bladder tumor resections before chemohyperthermia had higher recurrence-free survival (p = 0.01). On multivariable analysis the highly recurrent cancer criteria remained independently associated with decreased recurrence-free survival (HR 2.40, 95% CI 1.30-4.43, p = 0.01). CONCLUSIONS: Chemohyperthermia is an effective approach to nonmuscle invasive bladder cancer for which standard intravesical treatments fail. Patients with highly recurrent disease before chemohyperthermia have lower recurrence-free survival. Furthermore, recurrence-free survival appears to improve with earlier chemohyperthermia. No significant differences were observed between the 2 chemotherapy agents.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Epirubicina/uso terapêutico , Hipertermia Induzida , Mitomicina/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estudos Prospectivos , Fatores de Tempo , Neoplasias da Bexiga Urinária/tratamento farmacológico
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