cisplatin
Sources réglementaires consultées
Indications approuvées
- Traitement combiné du cancer testiculaire avancé.
- Traitement du cancer de l’ovaire avancé, en association ou en monothérapie selon le protocole.
- Monothérapie du cancer de la vessie avancé.
- Traitement des tumeurs métastatiques ou avancées de la tête et du cou, du poumon non à petites cellules ou à petites cellules, et en association à la radiothérapie pour le carcinome du col utérin.
Contre-indications
Absolues
- Hypersensibilité au cisplatine ou à d’autres composés du platine.
- Clairance de la créatinine inférieure à 60 ml/min selon la fiche CIMA.
- Déshydratation.
- Myélosuppression.
- Déficit auditif préexistant.
- Neuropathie causée par le cisplatine.
- Vaccination concomitante contre la fièvre jaune.
- Allaitement.
Mises en garde cliniques
- Mise en garde encadrée · Il peut provoquer une néphrotoxicité cumulative grave, y compris une insuffisance rénale aiguë. Assurer une hydratation adéquate et surveiller la fonction rénale, le magnésium, le sodium, le potassium et le calcium avant et pendant chaque cycle. — DailyMed, Cisplatin injection set_id 508496cb-3441-46b3-a4fe-e0d440e6adc6
- Mise en garde encadrée · Il peut provoquer une neuropathie périphérique cumulative, irréversible et invalidante. Effectuer une évaluation neurologique régulière et réévaluer la dose ou la poursuite du traitement en cas de symptômes. — DailyMed, Cisplatin injection set_id 508496cb-3441-46b3-a4fe-e0d440e6adc6
- Mise en garde encadrée · Il est hautement émétisant. Administrer une prémédication antiémétique efficace et surveiller la déshydratation et les troubles électrolytiques. — DailyMed, Cisplatin injection set_id 508496cb-3441-46b3-a4fe-e0d440e6adc6
- Mise en garde encadrée · La myélosuppression peut être grave ou mortelle par infection. Surveiller l’hémogramme et différer, réduire ou arrêter selon la récupération. — DailyMed, Cisplatin injection set_id 508496cb-3441-46b3-a4fe-e0d440e6adc6
- Mise en garde majeure · L’ototoxicité peut être irréversible et plus grave en pédiatrie. Réaliser une audiométrie avant le traitement et avant chaque cycle ; une perte auditive tardive peut survenir. — AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107
- Mise en garde majeure · Des réactions anaphylactiques et une réactivité croisée avec d’autres sels de platine peuvent survenir. Administrer dans un lieu disposant d’un support immédiat pour traiter une réaction grave. — AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107
Interactions médicamenteuses
- SévèreMédicaments néphrotoxiques ou ototoxiques
Mécanisme: Ils peuvent augmenter de façon additive la toxicité rénale ou auditive.
Recommandation: Éviter l’association si possible ; si elle est indispensable, renforcer la surveillance rénale, électrolytique et auditive.
AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107https://cima.aemps.es/cima/dochtml/ft/62107/FT_62107.htmlDailyMed, Cisplatin injection set_id 508496cb-3441-46b3-a4fe-e0d440e6adc6https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=508496cb-3441-46b3-a4fe-e0d440e6adc6
- ModéréeLithium
Mécanisme: Le cisplatine peut réduire les concentrations sanguines de lithium.
Recommandation: Surveiller la concentration de lithium et coordonner l’ajustement avec l’équipe prescriptrice.
AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107https://cima.aemps.es/cima/dochtml/ft/62107/FT_62107.html
- ModéréeAnticoagulants oraux
Mécanisme: La chimiothérapie peut modifier l’anticoagulation de façon variable.
Recommandation: Surveiller l’INR plus fréquemment.
AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107https://cima.aemps.es/cima/dochtml/ft/62107/FT_62107.html
- ModéréePhénytoïne et autres anticonvulsivants
Mécanisme: Le cisplatine peut réduire leurs concentrations et compromettre le contrôle des crises.
Recommandation: Surveiller les concentrations et la réponse clinique ; ajuster si nécessaire.
AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107https://cima.aemps.es/cima/dochtml/ft/62107/FT_62107.html
- SévèreVaccins vivants
Mécanisme: L’immunosuppression augmente le risque d’infection vaccinale généralisée ; le vaccin contre la fièvre jaune est contre-indiqué.
Recommandation: Éviter les vaccins vivants pendant le traitement et pendant 3 mois après ; ne pas administrer le vaccin contre la fièvre jaune.
AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107https://cima.aemps.es/cima/dochtml/ft/62107/FT_62107.html
- SévèrePaclitaxel
Mécanisme: Administrer le cisplatine avant le paclitaxel réduit d’environ 33 % la clairance du paclitaxel et peut augmenter la neurotoxicité.
Recommandation: Coordonner l’ordre du protocole et surveiller la neurotoxicité.
AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107https://cima.aemps.es/cima/dochtml/ft/62107/FT_62107.html
- SévèrePyridoxine avec altrétamine
Mécanisme: L’association avec le cisplatine a été liée à une moins bonne réponse.
Recommandation: Éviter l’association.
AEMPS CIMA, CISPLATINO PHARMACIA, registro 62107https://cima.aemps.es/cima/dochtml/ft/62107/FT_62107.html
Effets indésirables
Communs (≥1%)
leucopénie · thrombopénie · anémie · nausées et vomissements · anorexie · diarrhée · néphrotoxicité · ototoxicité
Rares mais graves
leucémie aiguë secondaire · microangiopathie thrombotique ou syndrome hémolytique et urémique · anaphylaxie · syndrome d’encéphalopathie postérieure réversible · cécité ou névrite optique · infarctus du myocarde ou arrêt cardiaque
Grossesse et allaitement
Catégorie FDA: D
Ancienne catégorie D de la FDA : il peut nuire au fœtus. Informer du risque en cas d’utilisation pendant la grossesse. Le cisplatine et ses métabolites actifs passent dans le lait ; ne pas allaiter pendant le traitement ni pendant 4 semaines après la dernière dose.
Bibliographie récente (PubMed)
Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus
Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes. In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point. In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group. Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherap
In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis. TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235. From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (34
Cisplatin is an effective chemotherapeutic agent for various solid tumours, but its use is limited by adverse effects in normal tissues. In particular, cisplatin is nephrotoxic and can cause acute kidney injury and chronic kidney disease. Preclinical studies have provided insights into the cellular and molecular mechanisms of cisplatin nephrotoxicity, which involve intracellular stresses including DNA damage, mitochondrial pathology, oxidative stress and endoplasmic reticulum stress. Stress responses, including autophagy, cell-cycle arrest, senescence, apoptosis, programmed necrosis and inflammation have key roles in the pathogenesis of cisplatin nephrotoxicity. In addition, emerging evidence suggests a contribution of epigenetic changes to cisplatin-induced acute kidney injury and chronic kidney disease. Further research is needed to determine how these pathways are integrated and to identify the cell type-specific roles of critical molecules involved in regulated necrosis, inflammation and epigenetic modifications in cisplatin nephrotoxicity. A number of potential therapeutic targets for cisplatin nephrotoxicity have been identified. However, the effects of renoprotective strategies on the efficacy of cisplatin chemotherapy needs to be thoroughly evaluated. Further research using tumour-bearing animals, multi-omics and genome-wide association studies will enable a comprehensive understanding of the complex cellular and molecular mechanisms of cisplatin nephrotoxicity and potentially lead to the identification of specific targets to protect the kidney without compromising the chemotherapeutic efficacy of cisplatin.
No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy. In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes. A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively. Combination therapy with nivolumab plus gemcitabine-cisplatin resu