- MeSH
- glukokortikoidy aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom * chirurgie diagnóza farmakoterapie patologie MeSH
- mitomycin aplikace a dávkování MeSH
- nádory spojivky * chirurgie diagnóza farmakoterapie patologie MeSH
- poruchy pigmentace etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Cíl studie: Instilace mitomycinu C (MMC) po transuretrální resekci nádoru močového měchýře (TURBT) snižuje riziko recidivy karcinomu močového měchýře. Cílem práce bylo zhodnocení využívání jednorázové pooperační instilace chemoterapeutika po TURBT na našem pracovišti a důvodů jejího nepodání. Pacienti a metody: Retrospektivní vyhodnocení souboru pacientů po TURBT v letech 2016–2022. Byl hodnocen celkový počet TURBT a celkový počet jednorázových instilací MMC (SS-MMC). Zvláště byla vyhodnocena skupina pacientů, u které nebyl zřejmý důvod k nepodání MMC. Dále byly hodnoceny důvody nepodání MMC. Výsledky: Ve sledovaném období bylo prove - deno 735 TURBT u 538 mužů a 197 žen (průměrný věk 71 let, medián 75 let) a podáno 211 SS-MMC (28,7 %). Po vyřazení pacientů s makroskopicky patrným reziduálním tumorem a paliativní endoresekcí (n = 102) a pacientů s endoresekcí pro jiné důvody než nádor močového měchýře (n = 24) bylo provedeno 609 TURBT, kdy bylo možné aplikovat MMC. V této skupině bylo zastoupení SS-MMC 34,7 %. Nejčastějším identifikovaným důvodem nepodání MMC (n = 398) byla hematurie (n = 83, 20,9 %), perforace stěny močového měchýře (n = 66, 16,6 %) a alergie (n = 4, 1 %). U 245 pacientů (61,6 %) nebylo možné důvod nepodání dohledat. Snížení počtu aplikací v letech 2019 a 2020 bylo dáno výpadkem dostupnosti MMC a epidemií COVID-19. Závěr: Údajů o reálné praxi jednorázové instilace chemoterapeutika po TURBT je málo a svědčí spíše pro její nízké využití. Dle našich dat je podaná přibližně u třetiny potenciálně vhodných pacientů. Interpretaci výsledků ztěžuje nedostatek informací o důvodech nepodání MMC při retrospektivní analýze dokumentace.
Aim of Study: Mitomycin C (MMC) instillation after transurethral resection of bladder tumour (TURBT) reduces the risk of bladder cancer recurrence. The aim of this study was to evaluate the use of single postoperative chemotherapy instillation after TURBT at our institution and the reasons for not administering it. Patients and Methods: A retrospective evaluation of a cohort of patients undergoing TURBT from 2016-2022. The total number of TURBTs and the total number of single-shot MMC instillations (SS-MMC) were evaluated. In particular, the group of patients with no obvious reason for not administering MMC was evaluated. Furthermore, the reasons for not administering MMC were evaluated. Results: During the follow-up period, 735 TURBTs were performed in 538 men and 197 women (mean age 71 years, median 75 years) and 211 SS-MMCs (28.7%) were administered. After excluding patients with macroscopically evident residual tumor and palliative endoresection (n = 102) and patients with endoresection for reasons other than bladder cancer (n = 24), 609 TURBTs were performed when MMCs could be instillated. In this group, the representation of SS-MMC was 34.7%. The most common identified reason for not administering SS-MMC (n = 398) was hematuria (n = 83, 20.9%), bladder wall perforation (n = 66, 16.6%), and allergy (n = 4, 1%). In 245 patients (61.6%), the reason for not administering could not be traced. The reduction in the number of applications in 2019 and 2020 was due to the lack of availability of MMC and the COVID-19 epidemic. Conclusion: Data on the actual practice of single instillation of chemotherapeutic agents after TURBT are scarce and suggest that its use is rather low. According to our data, it is administered in approximately one third of potentially suitable patients. Interpretation of the results is hampered by the lack of information on the reasons for not administering MMC in retrospective analysis of the documentation.
BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.
- MeSH
- adjuvantní chemoterapie metody MeSH
- aplikace intravezikální MeSH
- hodnocení rizik MeSH
- invazivní růst nádoru * MeSH
- lidé MeSH
- lokální recidiva nádoru prevence a kontrola MeSH
- mitomycin * terapeutické užití aplikace a dávkování MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie MeSH
- protinádorová antibiotika * terapeutické užití aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.
- MeSH
- adjuvantní chemoterapie MeSH
- aplikace intravezikální MeSH
- BCG vakcína terapeutické užití aplikace a dávkování MeSH
- cystektomie metody MeSH
- epirubicin aplikace a dávkování MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitomycin aplikace a dávkování terapeutické užití MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * patologie terapie farmakoterapie mortalita MeSH
- přežití bez známek nemoci MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged <4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: <0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade >1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.
- MeSH
- akutní lymfatická leukemie * etiologie MeSH
- busulfan * analogy a deriváty MeSH
- dítě MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli * etiologie MeSH
- předškolní dítě MeSH
- příprava pacienta k transplantaci škodlivé účinky MeSH
- recidiva MeSH
- thiotepa terapeutické užití MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
CONTEXT: The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer (NMIBC) have not become accepted. OBJECTIVE: To assess the treatment outcomes of chemoablation for NMIBC and to compare its safety with that of the standard treatment, transurethral resection of bladder tumors (TURBT) followed by intravesical therapy. EVIDENCE ACQUISITION: Multiple databases were queried in July 2022 for studies investigating the complete response (CR) rates and adverse events in NMIBC patients treated with chemoablation using mitomycin C (MMC), gemcitabine, epirubicin, or bacillus Calmette-Guérin. EVIDENCE SYNTHESIS: Overall, 23 studies comprising 1199 patients were eligible for this meta-analysis. Among these studies, 20 assessed the efficacy of chemoablation and three compared the treatment outcomes of MMC chemoablation versus standard treatment. Among patients treated with weekly administration of any agent, the pooled CR rates at initial assessment were 50.9% (95% confidence interval [CI]: 45.9-55.9) for the marker lesion and 47.5% (95% CI: 36.5-58.7) for well-selected NMIBC (ie, small tumors and/or a small number of tumors). Novel regimens for chemoablation such as MMC-gel (70.6%, 95% CI: 60.1-79.3) and an intensive MMC regimen (64.7%, 95% CI: 56.2-72.3) provided better CR rates in well-selected NMIBC patients. Comparable CR rates were noted irrespective of tumor multiplicity, whereas tumor size <5 mm was associated with a higher CR rate than tumor size ≥5 mm (odds ratio: 0.36, 95% CI: 0.17-0.79). The novel intensive MMC regimen resulted in lower rates of dysuria and urinary frequency than standard treatment. CONCLUSIONS: Despite the lack of long-term outcomes, chemoablation appears to be a promising treatment option for well-selected NMIBC patients and can potentially help avoid unnecessary TURBT, specifically in some elderly patients with intermediate-risk NMIBC. Further well-designed studies with larger cohorts are necessary to address the differential tolerability and long-term anticancer efficacy of this resurging approach. PATIENT SUMMARY: Bladder instillation therapy has a potential ablative effect for well-selected non-muscle-invasive bladder cancer. This can lead to the omission of an unnecessary surgical treatment.
- MeSH
- aplikace intravezikální MeSH
- gemcitabin MeSH
- lidé MeSH
- mitomycin MeSH
- nádory močového měchýře neinvadující svalovinu * MeSH
- nádory močového měchýře * farmakoterapie chirurgie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- MeSH
- aplikace intravezikální MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- mitomycin * terapeutické užití MeSH
- nádory močového měchýře * farmakoterapie chirurgie MeSH
- protinádorová antibiotika terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- randomizované kontrolované studie MeSH
Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.
- MeSH
- epirubicin MeSH
- kyselina olejová MeSH
- lokální recidiva nádoru patologie MeSH
- mitomycin terapeutické užití MeSH
- močový měchýř * patologie MeSH
- myši MeSH
- nádory močového měchýře * farmakoterapie prevence a kontrola patologie MeSH
- protinádorová antibiotika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Jako standardní přípravný režim se před podáním autologní transplantace krvetvorných buněk (ASCT) u relabujících či refrakterních lymfomů používal BEAM, tedy carmustine (BCNU) v kombinaci s etoposidem, cytarabinem a melfalanem. Recentní nedostatek BCNU však vedl k nutnosti přechodu na alternativní režim, kterým se v našem centru stal od července 2018 režim obsahující thiotepu, tzv. TEAM. Rozhodli jsme se retrospektivně srovnat gastrointestinální (GIT) toxicitu obou přípravných režimů. Zahrnuli jsme 142 konsekutivně autologně transplantovaných pacientů (BEAM = 82, TEAM = 60), z nichž 31 % mělo difuzní velkobuněčný B-lymfom (DLBCL), 20 % Hodgkinův lymfom (HL), 15 % lymfom z plášťových buněk (MCL), 14 % T-buněčné lymfomy (T-NHL) a zbylých 20 % ostatní druhy non-Hodgkinových lymfomů (NHL). Obě kohorty byly srovnatelné stran věku pacientů, zastoupení diagnóz a stavu nemoci v době ASCT. V distribuci jednotlivých stupňů GIT toxicity nebyl mezi dvěma přípravnými režimy nalezen statisticky signifikantní rozdíl, a to ani po seskupení všech stupňů do dvou hlavních skupin pacientů (grade 0 + 1 vs. grade 2–4). Pacienti dostávající režim TEAM však častěji dospěli k potřebě parenterální výživy, a to ve 20 případech (33 %) oproti pouhým 13 případům (16 %) u režimu BEAM (p = 0,04). Nerelapsová mortalita (NRM) byla u obou režimů srovnatelně nízká, během hospitalizace byla 0 %, ve 3 měsících pak 2 % shodně pro oba přípravné režimy (p = 1,0). Nezaznamenali jsme statisticky signifikantní rozdíl v celkovém přežití (overal survival; OS) ani v přežití do známek progrese (progression free survival; PFS) (p = 0,59 pro OS, p = 0,1 pro PFS).
The BEAM regimen, i.e., carmustine (BCNU) in combination with etoposide, cytarabine, and melphalan was used as standard conditioning prior to autologous hematopoietic cell transplantation (ASCT) in relapsed or refractory lymphomas. However, the recent unavailability of BCNU necessitated the use of an alternative regimen, which in our centre became from July 2018 the so-called TEAM regimen containing thiotepa. We decided to retrospectively compare the gastrointestinal (GIT) toxicity of both conditioning regimens. We included 142 consecutive autologous transplant patients (BEAM = 82, TEAM = 60), of whom 31% had diffuse large B-cell lymphoma (DLBCL), 20% Hodgkin‘s lymphoma (HL), 15 % mantle cell lymphoma (MCL), 14% T-cell lymphomas (T-NHL) and the remaining 20% other types of non-Hodgkin lymphomas (NHL). Both cohorts were comparable in terms of patient age, prevalence of diagnoses, and disease status at the time of ASCT. There was no statistically significant difference in the distribution of the grades of GIT toxicity between the two cohorts, even after grouping all grades into two main groups of patients (grade 0+1 vs. grade 2–4). Patients receiving the TEAM regimen were more likely to require parenteral nutrition, namely in 20 cases (33%) versus only 13 cases (16%) in the BEAM regimen (P = 0.04). Non-relapse mortality (NRM) was comparably low for both regimens – 0% during hospitalization and 2% at 3 months for both conditioning regimens (P = 1.0). We also compared overall survival (OS) and progression-free survival (PFS): there was no statistically significant difference between the two cohorts (P = 0.59 for OS, P = 0.1 for PFS).
- MeSH
- autologní transplantace MeSH
- dospělí MeSH
- karmustin škodlivé účinky terapeutické užití MeSH
- kombinovaná farmakoterapie metody škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom * farmakoterapie MeSH
- nežádoucí účinky léčiv epidemiologie MeSH
- příprava pacienta k transplantaci * metody škodlivé účinky statistika a číselné údaje MeSH
- protinádorové látky škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- thiotepa škodlivé účinky terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
