procarbazine
Sources réglementaires consultées
Indications approuvées
- Chez l’adulte, en association à d’autres antinéoplasiques pour le lymphome de Hodgkin ; il est également utilisé dans les lymphomes avancés et les tumeurs cérébrales selon les protocoles oncologiques.
- Chez l’enfant et l’adolescent de 2–18 ans, en association pour le lymphome de Hodgkin.
Contre-indications
Absolues
- Hypersensibilité à la procarbazine.
- Réserve médullaire insuffisante ou leucopénie, thrombopénie ou anémie sévère.
- Insuffisance rénale ou hépatique sévère.
- Grossesse.
- Allaitement.
Mises en garde cliniques
- Mise en garde encadrée · Il doit être administré sous la supervision d’un clinicien expérimenté en antinéoplasiques, avec une surveillance clinique et biologique adéquate. — DailyMed, MATULANE set_id 1aa75a3a-18c9-49e1-91a6-293d0b7da756
- Mise en garde majeure · Contrôler l’hémogramme et les fonctions rénale et hépatique avant chaque cycle ; pendant le traitement, contrôler l’hémogramme au moins deux fois par semaine ou tous les 3–4 jours et les fonctions rénale et hépatique chaque semaine. — AEMPS CIMA, NATULAN 50 mg, registro 42248
- Mise en garde majeure · Suspendre en cas de cytopénies importantes, symptômes neurologiques, hypersensibilité, diarrhée, stomatite ou vomissements persistants. Tremblements, coma et convulsions ont été rapportés en pédiatrie. — AEMPS CIMA, NATULAN 50 mg, registro 42248
- Mise en garde majeure · Elle est mutagène et peut provoquer infertilité, azoospermie permanente, leucémie myéloïde aiguë et autres cancers secondaires. Envisager la préservation de la fertilité avant le traitement. — AEMPS CIMA, NATULAN 50 mg, registro 42248
- Mise en garde majeure · La procarbazine agit comme inhibiteur faible de la monoamine oxydase. Éviter les aliments riches en tyramine, l’alcool et les sympathomimétiques afin de réduire les crises hypertensives et autres réactions graves. — AEMPS CIMA, NATULAN 50 mg, registro 42248
Interactions médicamenteuses
- SévèreAliments riches en tyramine
Mécanisme: L’inhibition faible de la monoamine oxydase peut déclencher une réaction hypertensive.
Recommandation: Éviter les fromages affinés, extraits de levure et autres aliments riches en tyramine pendant le traitement.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- SévèreAlcool
Mécanisme: Il peut provoquer une réaction de type disulfirame et majorer la dépression du système nerveux central.
Recommandation: Ne pas consommer d’alcool pendant le traitement.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- SévèreSympathomimétiques et décongestionnants
Mécanisme: L’inhibition de la monoamine oxydase peut augmenter la réponse pressive.
Recommandation: Éviter l’association, y compris les produits sans ordonnance.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- SévèreDépresseurs du système nerveux central, anticholinergiques, tricycliques et phénothiazines
Mécanisme: Peut majorer la sédation, l’hypotension et les effets anticholinergiques.
Recommandation: Éviter ou réduire la dose sous surveillance spécialisée.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- ModéréeAntiépileptiques inducteurs enzymatiques
Mécanisme: Une fréquence accrue de réactions d’hypersensibilité a été observée.
Recommandation: Préférer un antiépileptique non inducteur si possible.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
- SévèreVaccins vivants
Mécanisme: L’immunosuppression augmente le risque d’infection vaccinale généralisée.
Recommandation: Éviter pendant le traitement immunosuppresseur.
AEMPS CIMA, NATULAN 50 mg, registro 42248https://cima.aemps.es/cima/dochtml/ft/42248/FT_42248.html
Effets indésirables
Communs (≥1%)
infections · leucopénie · thrombopénie · anémie · anorexie · nausées · vomissements · alopécie
Rares mais graves
leucémie myéloïde aiguë ou syndrome myélodysplasique · pancytopénie ou aplasie médullaire · anaphylaxie ou angio-œdème · convulsions ou coma · pneumopathie interstitielle · hépatotoxicité sévère · syndrome de Stevens-Johnson ou nécrolyse épidermique toxique
Grossesse et allaitement
Elle est contre-indiquée pendant la grossesse en raison de la fœtotoxicité et du risque de malformations, surtout au premier trimestre. Utiliser une contraception adéquate pendant le traitement et pendant 6 mois après chez les femmes et 3 mois après chez les hommes. Elle peut provoquer une infertilité permanente ; envisager une cryoconservation. Ne pas allaiter pendant le traitement.
Bibliographie récente (PubMed)
Malignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%. Approximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). Magnetic resonance imaging before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation. For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%; hazard ratio [HR], 0.6 [95% CI, 0.5-0.7]; P < .001). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients; HR, 0.60 [95% CI, 0.35-1.03]; P = .06) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients; HR, 0.61 [95% CI, 0.40-0.94]; P = .02). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation. The incidence of primary malignant brain tumors is approximat
Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1-3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1-7), and prednisone (40 mg/m2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalT
Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decrease
To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. Fifty-nine randomized trials focusing on therapeutic management were identified. Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.
Anaplastic oligodendrogliomas are a type of glioma that occurs primarily in adults but are also found in children. These tumors are genetically defined according to the mutations they harbor. Grade II and grade III tumors can be differentiated most of the times by the presence of anaplastic features. The earliest regimen used for the treatment of these tumors was procarbazine, lomustine, and vincristine. The treatment modalities have shifted over time, and recent studies are considering immunotherapy as an option as well. This review assesses the latest management modalities along with the pathways involved in the pathogenesis of this malignancies.