vincristine
Sources réglementaires consultées
Indications approuvées
- Leucémie aiguë ; lymphome de Hodgkin ou non hodgkinien ; rhabdomyosarcome, neuroblastome, tumeur de Wilms, ostéosarcome, mycosis fongoïde, sarcome d’Ewing, cancer du sein, mélanome, cancer bronchique à petites cellules et tumeurs gynécologiques pédiatriques ; également purpura thrombopénique idiopathique vrai réfractaire à la splénectomie et à une courte corticothérapie, selon le protocole.
Contre-indications
Absolues
- Hypersensibilité à la vincristine ou à ses excipients.
- Administration intrathécale ; neuropathie démyélinisante de type Charcot-Marie-Tooth ; radiothérapie de la région hépatique ; grossesse ; allaitement.
Mises en garde cliniques
- VOIE INTRAVEINEUSE UNIQUEMENT. L’ADMINISTRATION INTRATHÉCALE EST MORTELLE. Étiqueter et séparer la préparation pour prévenir les erreurs de voie. — CIMA/AEMPS, ficha técnica 62378
- La neurotoxicité est limitante : surveiller neuropathie, iléus, douleur, atteintes crâniennes et SIADH. C’est un vésicant et l’extravasation peut provoquer une ulcération. Administrer systématiquement une prophylaxie de la constipation à chaque patient. — CIMA/AEMPS, ficha técnica 62378
- Une administration intrathécale accidentelle est une urgence immédiate pouvant entraîner paralysie ou décès. Le retrait du liquide céphalorachidien et le lavage sous-arachnoïdien au Ringer lactate ne garantissent pas la prévention des lésions ; activer immédiatement la prise en charge spécialisée d’urgence. Pendant les 3–4 premières semaines de l’induction de la leucémie, contrôler fréquemment l’acide urique et prévenir la néphropathie uratique par hydratation, alcalinisation ou allopurinol selon le protocole. — CIMA/AEMPS, ficha técnica 62378
Interactions médicamenteuses
- SévèreAntifongiques azolés
Mécanisme: Itraconazole, fluconazole ou voriconazole peuvent augmenter la neurotoxicité de la vincristine.
Recommandation: Éviter l’association si une alternative existe ; si indispensable, renforcer la surveillance neurologique.
CIMA/AEMPS, ficha técnica 62378
- SévèreMitomycine C
Mécanisme: Peut provoquer bronchospasme et détresse respiratoire.
Recommandation: Surveiller les symptômes respiratoires et arrêter s’ils apparaissent.
CIMA/AEMPS, ficha técnica 62378
- SévèreL-asparaginase
Mécanisme: La séquence peut modifier la toxicité de la vincristine.
Recommandation: Administrer la vincristine 12 à 24 heures avant la L-asparaginase afin de réduire la toxicité.
CIMA/AEMPS, ficha técnica 62378
- SévèreVaccins vivants
Mécanisme: L’immunosuppression peut augmenter la réplication vaccinale et le risque d’infection disséminée.
Recommandation: Éviter sauf évaluation spécialisée exceptionnelle après vérification de la numération et du statut immunitaire.
CIMA/AEMPS, ficha técnica 62378
Grossesse et allaitement
La grossesse et l’allaitement sont contre-indiqués. Un conseil oncologique spécifique sur la contraception est requis.
Bibliographie récente (PubMed)
Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups. Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX Clinic
Peripheral neuropathy, defined as damage to peripheral nerves, affects approximately 1% of adults worldwide. More than 200 causes of peripheral neuropathy exist, with symptoms ranging in severity from mild toe numbness to debilitating symptoms that can require a wheelchair. Diabetes is the most common cause of neuropathy, affecting approximately 206 million people worldwide. Peripheral neuropathy is typically length-dependent, which means that symptoms appear in the longest nerve axons (toes) and progress proximally over time. Peripheral neuropathy is typically symmetric and affects sensory axons more than motor axons. Diabetic neuropathy, which is often associated with both sensory symptoms, such as pain, tingling, or numbness; mild weakness; and autonomic symptoms, such as orthostatic hypotension, accounts for more than 50% of peripheral neuropathy in Western populations. Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B12; and monoclonal gammopathies. Up to 27% of adults with neuropathy have no identifiable etiology for their neuropathy after diagnostic testing. Recommended initial testing includes blood glucose (for diabetes), serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation (for monoclonal gammopathies). First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline. Pain often persists despite medical management. At least a 50% reduction in pain was observed in 38% of those with painful diabetic pe
For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripher
Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence-based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell-containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence-based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non-PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Stateme
Large B-cell lymphoma, the prototype of aggressive non-Hodgkin lymphomas, is both the most common lymphoma and accounts for the highest global burden of lymphoma-related deaths. For nearly 4 decades, the goal of treatment has been "cure", first based on CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and subsequently with rituximab plus CHOP. However, there is significant clinical, pathologic, and biologic heterogeneity, and not all patients are cured. Understanding and incorporating this biologic heterogeneity into treatment decisions unfortunately is not yet standard of care. Despite this gap, we now have significant advances in frontline, relapsed, and refractory settings. The POLARIX trial shows, for the first time, improved progression-free survival in a prospective randomized phase 3 setting. In the relapsed and refractory settings, there are now many approved agents/regimens, and several bispecific antibodies poised to join the arsenal of options. While chimeric antigen receptor T-cell therapy is discussed in detail elsewhere, it has quickly become an excellent option in the second-line setting and beyond. Unfortunately, special populations such as older adults continue to have poor outcomes and be underrepresented in trials, although a new generation of trials aim to address this disparity. This brief review will highlight the key issues and advances that offer improved outcomes to an increasing portion of patients.