oxaliplatin
Sources réglementaires consultées
Indications approuvées
- En association au fluorouracile et à l’acide folinique pour le traitement adjuvant du cancer du côlon de stade III après résection complète.
- En association au fluorouracile et à l’acide folinique pour le traitement du cancer colorectal métastatique.
Contre-indications
Absolues
- Hypersensibilité à l’oxaliplatine ou à d’autres composés du platine.
- Myélosuppression initiale avec neutrophiles <2 × 10⁹/L ou plaquettes <100 × 10⁹/L selon la fiche CIMA.
- Neuropathie sensitive avec gêne fonctionnelle avant le premier cycle.
- Clairance de la créatinine <30 ml/min selon la fiche CIMA ; la FDA prévoit une réduction de dose plutôt qu’une contre-indication.
- Allaitement selon la fiche CIMA.
Mises en garde cliniques
- Mise en garde encadrée · Il peut provoquer une anaphylaxie grave ou mortelle à n’importe quel cycle. Arrêter immédiatement et définitivement en cas d’hypersensibilité et traiter la réaction. — DailyMed, Oxaliplatin injection set_id 1ac38523-480b-4c0f-97a1-7dfa1432923c
- Mise en garde majeure · La neuropathie sensitive aiguë et cumulative est limitante. Évaluer avant chaque cycle et avertir que le froid peut déclencher ou aggraver les symptômes aigus. — AEMPS CIMA, OXALIPLATINO ACCORD, registro 72386
- Mise en garde majeure · Contrôler l’hémogramme avant chaque cycle. Différer et ajuster en cas de neutropénie ou thrombopénie ; des sepsis, sepsis neutropéniques et coagulations intravasculaires disséminées mortels sont survenus. — AEMPS CIMA, OXALIPLATINO ACCORD, registro 72386
- Mise en garde majeure · Des vomissements ou diarrhées sévères peuvent provoquer déshydratation, iléus et insuffisance rénale. Une ischémie intestinale mortelle a été rapportée ; arrêter si elle est confirmée. — AEMPS CIMA, OXALIPLATINO ACCORD, registro 72386
- Mise en garde majeure · Des pneumopathies interstitielles et fibroses pulmonaires mortelles, un PRES, un allongement du QT et des arythmies ventriculaires ont été rapportés. Explorer les symptômes respiratoires ou neurologiques et surveiller le risque électrocardiographique. — AEMPS CIMA, OXALIPLATINO ACCORD, registro 72386
Interactions médicamenteuses
- SévèreMédicaments allongeant le QT
Mécanisme: Ils peuvent augmenter le risque d’allongement du QT et d’arythmies ventriculaires.
Recommandation: Éviter l’association si possible ; si elle est nécessaire, corriger les électrolytes et surveiller l’ECG.
AEMPS CIMA, OXALIPLATINO ACCORD, registro 72386https://cima.aemps.es/cima/dochtml/ft/72386/FT_72386.htmlDailyMed, Oxaliplatin injection set_id 1ac38523-480b-4c0f-97a1-7dfa1432923chttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1ac38523-480b-4c0f-97a1-7dfa1432923c
- ModéréeMédicaments associés à la rhabdomyolyse
Mécanisme: Ils peuvent augmenter le risque de lésion musculaire sévère.
Recommandation: Utiliser avec prudence et évaluer douleur, faiblesse et créatine kinase en cas de symptômes.
AEMPS CIMA, OXALIPLATINO ACCORD, registro 72386https://cima.aemps.es/cima/dochtml/ft/72386/FT_72386.html
- SévèreVaccins vivants ou atténués
Mécanisme: L’immunosuppression augmente le risque d’infection vaccinale généralisée.
Recommandation: Éviter pendant le traitement.
AEMPS CIMA, OXALIPLATINO ACCORD, registro 72386https://cima.aemps.es/cima/dochtml/ft/72386/FT_72386.html
Effets indésirables
Communs (≥1%)
neuropathie périphérique sensitive · nausées · vomissements · diarrhée · mucite · neutropénie · thrombopénie · anémie
Rares mais graves
anaphylaxie · coagulation intravasculaire disséminée · syndrome hémolytique et urémique · syndrome d’encéphalopathie postérieure réversible · fibrose pulmonaire ou pneumopathie interstitielle mortelle · ischémie intestinale mortelle · arythmie ventriculaire · rhabdomyolyse
Grossesse et allaitement
Il peut provoquer une toxicité embryofœtale. Vérifier la grossesse avant le traitement. Utiliser une contraception efficace pendant le traitement et pendant 9 mois après chez les femmes et 6 mois après chez les hommes ayant une partenaire susceptible d’être enceinte. Ne pas allaiter pendant le traitement ni pendant 3 mois après la dernière dose. Il peut altérer la fertilité.
Bibliographie récente (PubMed)
Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.
Glofitamab monotherapy induces durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma after two or more previous therapies, but has not previously been assessed as a second-line therapy. We investigated the efficacy and safety of glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) versus rituximab (R)-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma. The phase 3, randomised, open-label STARGLO trial was done at 62 centres in 13 countries in Asia and Australia, Europe, and North America. We recruited transplant-ineligible patients (aged ≥18 years) with histologically confirmed relapsed or refractory diffuse large B-cell lymphoma after one or more previous therapies. Patients were randomly assigned in permuted blocks (block size of six) via an interactive voice or web response system (2:1; stratified by 1 vs ≥2 previous lines of therapy and relapsed vs refractory status) to Glofit-GemOx (intravenous gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 plus glofitamab step-up dosing to 30 mg; for a total of eight cycles, plus four additional cycles of glofitamab monotherapy) or R-GemOx (intravenous gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 plus rituximab 375 mg/m2; for a total of eight cycles). The trial independent review committee, which evaluated all response-based endpoints, was masked to treatment assignment. The primary endpoint was overall survival. Efficacy analyses were by intention to treat in all randomly assigned patients. We present results from both the primary analysis (cutoff: March 29, 2023) and updated analysis after all patients had completed study therapy (cutoff: Feb 16, 2024). Safety analyses included all patients who received any study treatment. This study is registered with ClinicalTrials.gov, NCT04408638, and is ongoing (closed to recruitment). From Feb 23, 2021, to March 14, 2023, 274 patients were enrolled and randomly assigned to receive Glofit-GemOx (n=183) or R-GemOx (n=91)
First-line treatment with encorafenib plus cetuximab (EC) with or without chemotherapy (oxaliplatin, leucovorin, and fluorouracil [mFOLFOX6]) for BRAF V600E-mutated metastatic colorectal cancer, an aggressive subtype with a poor prognosis, was compared with standard care (chemotherapy with or without bevacizumab) in an open-label, phase 3 trial, which showed significance regarding one of the two primary end points, objective response according to blinded independent central review (odds ratio for EC+mFOLFOX6 vs. standard care, 2.44; one-sided P<0.001). This result led to accelerated Food and Drug Administration approval of this investigational combination therapy for BRAF V600E-mutated metastatic colorectal cancer, including as first-line therapy. Data on progression-free survival (the second primary end point) and an updated interim analysis of overall survival are now available. We randomly assigned patients with untreated BRAF V600E-mutated metastatic colorectal cancer to receive EC, EC+mFOLFOX6, or standard care. The two primary end points were objective response (reported previously) and progression-free survival according to blinded independent central review in the EC+mFOLFOX6 group and the standard-care group. The key secondary end point was overall survival. Significantly longer progression-free survival was seen with EC+mFOLFOX6 than with standard care (median, 12.8 vs. 7.1 months; hazard ratio for progression or death, 0.53; 95% confidence interval [CI], 0.41 to 0.68; P<0.001). In an interim analysis, overall survival was significantly longer with EC+mFOLFOX6 than with standard care (median, 30.3 vs. 15.1 months; hazard ratio for death, 0.49; 95% CI, 0.38 to 0.63; P<0.001). The incidence of serious adverse events during treatment was 46.1% with EC+mFOLFOX6 and 38.9% with standard care. Safety profiles were consistent with those known for each agent. This trial showed significantly longer progression-free survival and overall survival with first-line treat
Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that
No neoadjuvant treatment has been considered to be standard therapy for patients with resectable intrahepatic cholangiocarcinoma with high-risk factors for recurrence. The GOLP regimen (gemcitabine-oxaliplatin, lenvatinib, and an anti-programmed death 1 antibody) has shown promising efficacy with a manageable safety profile in advanced intrahepatic cholangiocarcinoma and biliary tract cancer. In a phase 2-3 trial, we randomly assigned, in a 1:1 ratio, patients with resectable high-risk intrahepatic cholangiocarcinoma to the neoadjuvant group (intravenous gemcitabine-oxaliplatin plus toripalimab every 3 weeks for three cycles and oral lenvatinib once daily for 9 weeks, followed by curative resection) or the control group (curative resection and no neoadjuvant treatment). All patients received adjuvant capecitabine for eight cycles after surgery. The primary end point was event-free survival. Secondary end points included overall survival and safety. A total of 178 patients underwent randomization (88 patients to the neoadjuvant group and 90 to the control group). At the interim analysis at a median follow-up of 16.9 months, the median event-free survival was significantly longer in the neoadjuvant group (18.0 months; 95% confidence interval [CI], 13.8 to 27.6) than in the control group (8.7 months; 95% CI, 7.2 to 12.4) (P<0.001). Overall survival at 24 months was 79% (95% CI, 70 to 90) in the neoadjuvant group and 61% (95% CI, 50 to 75) in the control group (hazard ratio for death, 0.43; 95% CI, 0.23 to 0.79; P = 0.005, which did not meet the significance criterion [two-sided alpha, 0.0019]). Across all treatment phases, adverse events occurred in 97% of the patients in the neoadjuvant group and in 70% of those in the control group. During the neoadjuvant phase, adverse events of grade 3 or higher occurred in 28% of the patients, and treatment-related adverse events of grade 3 or higher in 26%. No treatment-related adverse event led to death. Neoadjuvant GOLP led to