vinblastine
Sources réglementaires consultées
Indications approuvées
- Maladie de Hodgkin de stades III–IV ; lymphomes lymphocytaires ou histiocytaires ; mycosis fongoïde avancé ; cancer testiculaire avancé ; sarcome de Kaposi ; maladie de Letterer-Siwe ; et, plus rarement, choriocarcinome résistant et cancer du sein réfractaire à la chirurgie endocrinienne ou à l’hormonothérapie, en monothérapie ou en association selon le schéma autorisé.
Contre-indications
Absolues
- Hypersensibilité à la vinblastine, à d’autres alcaloïdes de la pervenche ou aux excipients.
- Leucopénie non liée à la tumeur ; infection bactérienne non contrôlée ; administration intrathécale ; allaitement.
Mises en garde cliniques
- VOIE INTRAVEINEUSE UNIQUEMENT. L’administration intrathécale peut être mortelle. Vérifier la voie avant préparation et administration. — CIMA/AEMPS, ficha técnica 37275
- C’est un vésicant : confirmer l’accès veineux et arrêter immédiatement en cas d’extravasation. Surveiller les leucocytes et ne pas augmenter au-delà de la dose qui les rapproche de 3 000/mm³. — CIMA/AEMPS, ficha técnica 37275
Interactions médicamenteuses
- SévèreMitomycine C
Mécanisme: Peut provoquer bronchospasme et toxicité pulmonaire sévère ou irréversible.
Recommandation: Surveiller étroitement la fonction respiratoire et arrêter en cas de symptômes.
CIMA/AEMPS, ficha técnica 37275
- SévèreItraconazole, érythromycine ou autres inhibiteurs du CYP3A4
Mécanisme: Ils peuvent augmenter l’exposition et la toxicité de la vinblastine.
Recommandation: Éviter si possible ou renforcer la surveillance de la neurotoxicité, de l’iléus et des autres toxicités.
CIMA/AEMPS, ficha técnica 37275
- SévèreVaccins vivants
Mécanisme: L’immunosuppression peut provoquer une infection vaccinale disséminée.
Recommandation: Les vaccins vivants ne sont pas recommandés pendant l’immunosuppression.
CIMA/AEMPS, ficha técnica 37275
- SévèreDigoxine
Mécanisme: La vinblastine peut réduire les concentrations et l’efficacité de la digoxine.
Recommandation: Surveiller concentrations et réponse clinique et ajuster la digoxine si nécessaire.
CIMA/AEMPS, ficha técnica 37275
- SévèrePhénytoïne
Mécanisme: La vinblastine peut réduire les concentrations de phénytoïne et augmenter le risque de crises.
Recommandation: Contrôler les concentrations et ajuster la phénytoïne selon la réponse.
CIMA/AEMPS, ficha técnica 37275
- SévèreBléomycine avec ou sans cisplatine
Mécanisme: Peut augmenter le risque de phénomène de Raynaud, gangrène et autres événements vasculaires ; la cisplatine peut aussi augmenter les concentrations de vinblastine.
Recommandation: Surveiller étroitement la toxicité vasculaire et celle de la vinblastine et coordonner le schéma oncologique.
CIMA/AEMPS, ficha técnica 37275
Grossesse et allaitement
Peut provoquer une atteinte fœtale. Utiliser une contraception efficace pendant le traitement et pendant au moins 3 mois après ; il est préférable de la prolonger jusqu’à 6 mois. Envisager la conservation du sperme avant le traitement. Ne pas allaiter.
Bibliographie récente (PubMed)
Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients. We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause. Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse even
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In the investigator-sponsored randomized phase II NIVAHL trial for early-stage unfavorable classical Hodgkin lymphoma (HL), two schedules of four cycles of nivolumab, doxorubicin, vinblastine, and dacarbazine followed by 30 Gy involved-site radiotherapy resulted in high complete remission rates and an unprecedented 1-year progression-free survival in 109 patients. In this article, we report the preplanned final analysis conducted three years after the registration of the last patient including long-term safety results. No survival events were observed since the primary analysis, and after a median follow-up (FU) of 41 months, the overall survival was 100% in both treatment groups. The progression-free survival was 98% and 100% in the sequential and concomitant nivolumab, doxorubicin, vinblastine, and dacarbazine treatment groups, respectively. At last FU, the mean forced expiratory pressure in one second was 95.5% (standard deviation 12.7%), the mean diffusion capacity for carbon monoxide adjusted for hemoglobin was 82.8% (standard deviation 15.4%), and the left ventricular ejection fraction was in the normal range in 95% of patients. Hypothyroidism requiring long-term medication occurred in 15% of patients, who were nearly exclusively female (87%). No second primary malignancies occurred, and no patient required corticosteroid treatment at last FU. Patient-reported normalized global quality-of-life score measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 improved over time. This preplanned FU analy
The optimal perioperative chemotherapy for patients with muscle-invasive bladder cancer is not defined. The VESPER (French Genito-Urinary Tumor Group and French Association of Urology V05) trial reported improved 3-year progression-free survival with dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) versus gemcitabine and cisplatin (GC) in patients who received neoadjuvant therapy, but not in the overall perioperative setting. In this Article, we report on the secondary endpoints of overall survival and time to death due to bladder cancer at 5-year follow-up. VESPER was an open-label, randomised, phase 3 trial done at 28 university hospitals or comprehensive cancer centres in France, in which adults (age ≤18 years and ≤80 years) with primary bladder cancer and histologically confirmed muscle-invasive urothelial carcinoma were randomly allocated (1:1; block size four) to treatment with dd-MVAC (every 2 weeks for a total of six cycles) or GC (every 3 weeks for a total of four cycles). Overall survival and time to death due to bladder cancer (presented as 5-year cumulative incidence of death due to bladder cancer) was analysed by intention to treat (ITT) in all randomly assigned patients. Overall survival was assessed by the Kaplan-Meier method with the treatment groups compared with log-rank test stratified for mode of administration of chemotherapy (neoadjuvant or adjuvant) and lymph node involvement. Time to death due to bladder cancer was analysed with an Aalen model for competing risks and a Fine and Gray regression model stratified for the same two covariates. Results were presented for the total perioperative population and for the neoadjuvant and adjuvant subgroups. The trial is registered with ClinicalTrials.gov, NCT01812369, and is complete. From Feb 25, 2013, to March 1, 2018, 500 patients were randomly assigned, of whom 493 were included in the final ITT population (245 [50%] in the GC group and 248 [50%] in the dd-MVAC group; 408 [8
The optimal perioperative chemotherapy regimen for patients with nonmetastatic muscle-invasive bladder cancer is not defined. Between February 2013 and March 2018, 500 patients were randomly assigned in 28 French centers and received either six cycles of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) once every 2 weeks or four cycles of gemcitabine and cisplatin (GC) once every 3 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). We report the primary end point of the GETUG-AFU V05 VESPER trial (ClinicalTrials.gov identifier: NCT01812369): progression-free survival (PFS) at 3 years. Secondary end points were time to progression and overall survival. Four hundred thirty-seven patients (88%) received neoadjuvant chemotherapy; 60% of patients received the planned six cycles in the dd-MVAC arm, 84% received four cycles in the GC arm, and thereafter, 91% and 90% of patients underwent surgery, respectively. Organ-confined response (< ypT3N0) was observed more frequently in the dd-MVAC arm (77% v 63%, P = .001). In the adjuvant group, 40% of patients received six cycles in the dd-MVAC arm, and 81% of patients received four cycles in the GC arm. For all patients in the clinical trial, 3-year PFS was improved in the dd-MVAC arm, but the study did not meet its primary end point (3-year rate: 64% v 56%, hazard ratio [HR] = 0.77 [95% CI, 0.57 to 1.02], P = .066); nevertheless, the dd-MVAC arm was associated with a significantly longer time to progression (3-year rate: 69% v 58%, HR = 0.68 [95% CI, 0.50 to 0.93], P = .014). In the neoadjuvant group, PFS at 3 years was significantly higher in the dd-MVAC arm (66% v 56%, HR = 0.70 [95% CI, 0.51 to 0.96], P = .025). In the VESPER trial, dd-MVAC improved 3-years PFS over GC. In the neoadjuvant group, a better bladder tumor local control and a significant improvement in 3-year PFS were observed in the dd-MVAC arm.