Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle invasive bladder cancer

Pijpers, Olga M; Hendricksen, Kees; Mostafid, Hugh; Jong, Florus C. de; Rosier, Marloes; Mayor, Nikhil; Jong, Joep J. de; Boormans, Joost L.

doi:10.1016/j.urolonc.2021.07.019

Cited by 26 publications

(23 citation statements)

References 22 publications

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“…In this cohort, 20 (35.1%) patients reported an adverse event (AE) during treatment, the most common of which were: rash, bladder spasm and urinary tract infection. AEs led to treatment cessation in 11 patients (28.9%), which is slightly higher than other reported studies (4%-28%) [16][17][18][19][20][21] ; this may suggest that older patient populations are less able to tolerate HIVEC instillations.…”

Section: Discussioncontrasting

confidence: 52%

“…Oncological outcomes (RFS, PFS and OS) were promising in this high-risk, pretreated cohort, and were similar to other high-risk NMIBC HIVEC studies. 17,18 HR-NMIBC represents almost one-third of the BC workload managed at our institution, 22 many of whom are unfit, or unwilling, to receive RC. Their management options are limited to adjuvant intravesical BCG, 8 which has high failure rates due to toxicity and recurrence 7,23,24 ; this is further compounded by poor BCG availability due to international supply shortages.…”

Section: Discussionmentioning

confidence: 99%

“…Hyperthemic MMC can be delivered using two models: radiofrequency-induced thermo-chemotherapy (RITE) using microwave radiation through a catheter device, and recombinant systems that use recirculation systems to externally heat and instil chemotherapeutic agents, such as, HIVEC. 25 With recent evidence emerging to support the use of hyperthermic MMC, in both its forms, as a potential adjuvant treatment in highrisk patients, [16][17][18][19][20][21]26,27 we established a specialist HIVEC clinic in our department. The primary focus was to explore the tolerability and acceptability of HIVEC treatment for patients with HR-NMIBC.…”

Section: Discussionmentioning

confidence: 99%

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Hyperthermic intravesical chemotherapy with mitomycin‐C for the treatment of high‐risk non‐muscle‐invasive bladder cancer patients

et al. 2022

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hyperthermic intravesical chemotherapy with mitomycin‐C for the treatment of high‐risk non‐muscle‐invasive bladder cancer patients

et al. 2022

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“…Prospective trials have been specifically conducted in different populations that are currently under analysis. Highly interesting results have recently confirmed that HIVEC MMC is valuable in the high-risk NMIBC population [ 23 , 24 ] and also in cases of BCG failure [ 25 , 26 ]. The present study, based on a real-world analysis, provides additional prognostic information on the value of adjunct HIVEC MMC, both in intermediate and high-risk groups, and aims to provide a rationale for selecting specific populations that could benefit from this approach.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain

Plata

Guerrero-Ramos

Garcia

et al. 2021

JCM

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(1) Background: Intravesical mitomycin-C (MMC) combined with hyperthermia is increasingly used in non-muscle invasive bladder cancer (NMIBC), especially in the context of a relative BCG shortage. We aim to determine real-world data on the long-term treatment outcomes of adjunct hyperthermic intravesical chemotherapy (HIVEC) with MMC and a COMBAT® bladder recirculation system (BRS); (2) Methods: A prospective observational trial was performed on patients with NMIBC treated with HIVEC using BRS in nine academic institutions in Spain between 2012–2020 (HIVEC-E). Treatment effectiveness (recurrence, progression and overall mortality) was evaluated in patients treated with HIVEC MMC 40mg in the adjuvant setting, with baseline data and a clinical follow-up, that comprise the Full Analysis Set (FAS). Safety, according to the number and severity of adverse effects (AEs), was evaluated in the safety (SAF) population, composed by patients with at least one adjunct HIVEC MMC instillation; (3) Results: The FAS population (n = 502) received a median number of 8.78 ± 3.28 (range 1–20) HIVEC MMC instillations. The median follow-up duration was 24.5 ± 16.5 (range 1–81) months. Its distribution, based on EAU risk stratification, was 297 (59.2%) for intermediate and 205 (40.8%) for high-risk. The figures for five-year recurrence-free and progression-free survival were 50.37% (53.3% for intermediate and 47.14% for high-risk) and 89.83% (94.02% for intermediate and 84.23% for high-risk), respectively. A multivariate analysis identified recurrent tumors (HR 1.83), the duration of adjuvant HIVEC therapy <4 months (HR 1.72) and that high-risk group (HR 1.47) were at an increased risk of recurrence. Independent factors of progression were high-risk (HR 3.89), recurrent tumors (HR 3.32) and the induction of HIVEC therapy without maintenance (HR 2.37). The overall survival was determined by patient age at diagnosis (HR 3.36) and the treatment duration (HR 1.82). The SAF population (n = 592) revealed 406 (68.58%) patients without AEs and 186 (31.42%) with at least one AE: 170 (28.72%) of grade 1–2 and 16 (2.7%) of grade 3–4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), skin rash (4.9%), spasms (3.7%) and hematuria (3.6%); (4) Conclusions: HIVEC using BRS is efficacious and well tolerated. A longer treatment duration, its use in naïve patients and the intermediate-risk disease are independent determinants of success. Furthermore, a monthly maintenance of adjunct MMC HIVEC diminishes the progression rate of NMIBC.

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“…der applizierten Dosen, Therapiedauer und verwendeter Instillationsschemata, sodass sowohl nach S3-als auch EAU-Leitlinie der Einsatz dieser Methode als experimentelles Verfahren betrachtet wird und damit nur im Rahmen klinischer Studien Anwendung finden sollte [1]. An dieser Stelle sei jedoch auf laufende Studien hingewiesen, die eine neuartige, extrakorporale Erwärmung von MMC (BRS, bladder recirculation system) zum Gegenstand haben [19]. Die randomisierten HIVEC-Studien (Hyperthermic IntraVEsical Chemotherapy) untersuchen den klinischen Stellenwert der HIVEC-Behandlung beim high-risk NMIBC wie auch beim BCG-refraktären Tumorgeschehen und machen Hoffnung auf eine Steigerung der lokalen Wirksamkeit von Chemoinstillationen.…”

Section: Geräteassistierte Intravesikale Therapie -Emda Und Chemohype...unclassified

Adjuvante Instillationstherapie des nicht muskelinvasiven Harnblasenkarzinoms – neue Optionen abseits von BCG und Mitomycin

Gakis

2022

Aktuelle Urol

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ZusammenfassungAufgrund der eingeschränkten Wirksamkeit der passiven Applikationsweise von BCG und Mitomycin-C (MMC) und in den letzten Jahren bestehenden BCG-Lieferengpässen ist eine Verbesserung der onkologischen Ergebnisse der adjuvanten Instillationstherapie beim nicht muskelinvasiven Harnblasenkarzinom (NMIBC) durch Entwicklung neuartiger Instillationsubstanzen und Applikationsweisen erforderlich.Gemcitabin ist als generisch verfügbare Substanz in zahlreichen randomisierten Studien in den verschiedenen Risikokonstellationen untersucht worden und zeigt insbesondere im BCG-unresponsiven Stadium ein verbessertes rezidivfreies Überleben im Vergleich zur BCG-Rechallenge und MMC. Eine neuartige Instillationsform stellt das Gemcitabin-intravesical-releasing system (GemRIS) dar, welches in der Kombination mit dem systemisch wirksamen Checkpointinhibitor Cetrelimab in derzeit anlaufenden klinischen Studien getestet wird. Hyperthermes intravesikales MMC (HIVEC), welches extrakorporal erwärmt und in die Blase zirkuliert, führt zu einer Konzentrationssteigerung von MMC in der Blasenwand und wird im Rahmen klinischer Studie bereits getestet. Nadofaragene firadenovec (rAd-IFN-α/Syn3) ist ein rekombinantes Adenovirus zur Steigerung der Interferon-alpha-Konzentration im Urothel und bietet erstmalig die Möglichkeit eine intravesikale Gentherapie für die urologischen Praxis zu etablieren. Daten aus einer aktuellen Phase-III Studie legen im BCG-unresponsiven Stadium eine höhere Wirksamkeit bei günstigerem Nebenwirkungsprofil im Vergleich zu Studien mit einer PD-(L)1-Monotherapie nahe. Opportuzumab monatox ist ein rekombinantes Fusionsprotein, welche nach EpCAM-Binding zu einer Freisetzung von Pseudomonas aeruginosa Exotoxin führt, welches hiernach einen zytotoxischen Zellschaden einleitet. N-803 ist ein Interleukin (IL)-15 Superagonist, welcher im Kombination mit BCG in einer Phase Ib Studie ein dauerhaftes komplettes Ansprechen über 72 Monate bei 9 intermediate/high-risk Patienten zeigte und bereits 2019 eine Vorabzulassung durch die FDA erhalten hat.

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Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle invasive bladder cancer

Cited by 26 publications

References 22 publications

Hyperthermic intravesical chemotherapy with mitomycin‐C for the treatment of high‐risk non‐muscle‐invasive bladder cancer patients

Hyperthermic intravesical chemotherapy with mitomycin‐C for the treatment of high‐risk non‐muscle‐invasive bladder cancer patients

Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain

Adjuvante Instillationstherapie des nicht muskelinvasiven Harnblasenkarzinoms – neue Optionen abseits von BCG und Mitomycin

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