valrubicin
Sources réglementaires consultées
Indications approuvées
- Carcinome in situ vésical réfractaire au BCG lorsque la cystectomie immédiate entraînerait une morbidité ou mortalité inacceptable.
Contre-indications
Absolues
- Vessie perforée ou muqueuse vésicale compromise ; infection urinaire active ; hypersensibilité aux anthracyclines ou à l’huile de ricin polyoxylée ; capacité vésicale <75 ml.
Mises en garde cliniques
- Usage intravésical uniquement. Confirmer l’intégrité vésicale avant chaque dose. En cas de perforation ou d’exposition systémique, surveiller la numération chaque semaine pendant 3 semaines. Réévaluer la cystectomie en l’absence de réponse complète à 3 mois ou en cas de récidive. — DailyMed, set_id e96f30a0-6662-11de-8f80-0002a5d5c51b
Grossesse et allaitement
Peut provoquer atteinte fœtale. Les femmes doivent utiliser une contraception pendant le traitement et 6 mois après ; les hommes pendant le traitement et 3 mois après. Ne pas allaiter pendant le traitement ni pendant 2 semaines après. Peut altérer la fertilité masculine.
Bibliographie récente (PubMed)
High-risk non-muscle-invasive bladder cancer (HR-NMIBC) presents a challenge to many physicians due to its ability to resist Bacillus Calmette-Guérin (BCG) intravesical therapy and the substantial rate of progression into muscle-invasive bladder cancer (MIBC). Patients who are BCG-unresponsive have worse prognosis and thus require further management including radical cystectomy (RC), which significantly impacts quality of life. Moreover, the ongoing worldwide shortage of BCG warrants the need for policies that prioritize drug use and utilize alternative treatment strategies. Hence, there is a significant unmet need for bladder preserving therapy in this subset of patients. To address this issue, we searched the relevant literature in PUBMED for articles published from 2019 through May of 2023 using appropriate keywords. All clinical trials of patients with HR-NMIBC treated with immune-related agents were retrieved from clinicaltrials.gov. Exploratory treatments for BCG-Unresponsive HR-NMIBC included immune checkpoint inhibitors (ICI), oncolytic viral therapy, cytokine agonists, and other immunomodulators targeting TLR, EpCaM, FGFR, MetAP2, and IDO1. Some combination therapies have been found to work synergistically and are preferred therapeutically over monotherapy. Three drugs-pembrolizumab, valrubicin, and most recently, nadofaragene firadenovec-vncg-have been FDA approved for the treatment of BCG-unresponsive NMIBC in patients who are ineligible for or decline RC. However, all explored treatment options tend to postpone RC rather than provide long-term disease control. Additional combination strategies need to be studied to enhance the effects of immunotherapy. Despite the challenges faced in finding effective therapies, many potential treatments are currently under investigation. Addressing the landscape of biomarkers, mechanisms of progression, BCG resistance, and trial design challenges in HR-NMIBC is essential for the discovery of new targets and the developm
With the exception of the FDA-approved valrubicin and pembrolizumab, there are no standard second-line treaments for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC). To provide a systematic review of the novel intravesically administered therapeutic agents for the salvage treatment of BCG-unresponsive NMIBC. Online search of the PubMed, EMBASE and Web of Science databases was performed. The endpoints of this review were to evaluate the efficacy of the agents in terms of complete response rates (CR) and durability of CR, overall survival, recurrence-free survival and cancer-specific survival and to report on their toxicity profile. A search on Clinicaltrials.gov was performed to identify ongoing clinical trials. 14 studies were included in this review. The critical clinical need for the development of an effective, safe and durable intravesical drug for the salvage treatment of high-risk NMIBC seems to be met mainly by intravesical gene therapy; in fact, data support the FDA-approved nadofaragene firadenovec as a potentially important therapeutic advancement in this context. Promising results are also being obtained by the combination of N-803/BCG and by innovative drug delivery systems. Considering the plethora of novel intravesical treatments that have completed phase II evaluation, one can reasonably expect that clinicians will soon have at their disposal new agents and treatment options for BCG-unresponsive NMIBC. In the near future, it will be up to the urologist to identify, for each specific patient, the right agent to use, based on safety, results and cost-effectiveness.
Most patients at first diagnosis of bladder cancer (BC) present with non muscle invasive disease (NMIBC). BCG intravesical therapy after transurethral resection of the bladder tumor is the gold standard in intermediate and high risk NMIBC patients. However, it is estimated that approximately 50% of these patients will present with BCG failure which increases their risk for progression to muscle invasive disease. Currently, the best option for these patients is radical cystectomy. Thus, it is of great interest to pursue new, therapeutic options for BCG failure patients to avoid the necessity of radical cystectomy. We hereby review novel treatment modalities for BCG failure patients. METHODS: This is a narrative review. Keywords for the search were BCG failure, BCG unresponsive, BCG refractory, BCG relapsing and BCG intolerance. Evidence was identified through a search for publications with a ''BCG unresponsive'' tag through 2020. Studies were selected if they contained clinical data on BCG unresponsive therapeutics with near-term availability. Clinical trial landscape evaluation for emerging therapies was performed by searching ClinicalTrials.gov for recruiting/ open interventional trials in 2020. RESULTS: Novel treatment modalities for BCG failure include intravesical chemotherapy, BCG re-challenge or combination of BCG with IFN-α2β, valrubicin, radiotherapy, electromotive drug administration, vicinium, chemohyperthermia, photodynamic therapy, gene therapy, vaccine therapy and immunotherapy. For patients in whom BCG has once failed a repeat course of BCG or BCG plus interferon appears to be a reasonable practice. Likewise, single agent gemcitabine may be considered a treatment modality. However, after 2 or more BCG failures, especially in patients with earlier relapses or cancer persistence, single agent intravesical chemotherapy with valrubicin, gemcitabine or docetaxel appears to be less active than doublet/triplet intravesical chemotherapy or mitomycin chemotherm
Bladder cancer (BCa) is one of the most common malignant tumors that cause death. Approximately 75%-85% of BCa develop into non-muscle-invasive bladder cancer (NMIBC). Bacillus Calmette-Guérin (BCG) is the gold standard for avoiding cystectomy in the treatment of NMIBC. Unfortunately, up to 30% of patients do not respond to BCG treatment, and up to 70% of BCG responders relapse. The United States Food and Drug Administration (FDA) approved valrubicin (1998) and pembrolizumab (2020) for the treatment of BCG-unresponsive (BCGu) NMBIC. However, the complete remission rate for valrubicin and pembrolizumab was only 16% and 40.6%, respectively. ALT-803 (N-803) is an IL-15 superagonist and reduces tumor burden by promoting the proliferation and activation of NK cells and CD8+ T cells. The FDA received (23 May 2022) and accepted to review (28 July 2022) the marketing submission of ALT-803 plus BCG for the treatment of BCGu NMIBC. However, the FDA previously rejected the application for oportuzumab monatox (OM) due to a lack of data comparing it with pembrolizumab on August 20, 2021. Interestingly, the clinical efficacy and safety of ALT-803 were higher than that of pembrolizumab and OM, suggesting that ALT-803 may be approved by FDA. This review aims to further knowledge of the preclinical and clinical evidence of ALT-803 in the treatment of NMIBC and discuss its translational potential.