cyclophosphamide
Sources réglementaires consultées
Indications approuvées
- Traitement oncologique systémique dans des protocoles spécialisés pour leucémies, lymphomes, myélome, tumeurs solides et conditionnement de greffe ; certaines maladies auto-immunes menaçant le pronostic vital.
Contre-indications
Absolues
- Hypersensibilité au cyclophosphamide ou à ses métabolites ; infection aiguë ; aplasie ou dépression médullaire préalable ; infection urinaire, toxicité urothéliale aiguë ou obstruction urinaire.
- Grossesse ou allaitement ; moins de 18 ans pour cette formulation contenant de l’alcool ; patients asiatiques porteurs d’un génotype ALDH2 mutant.
Mises en garde cliniques
- Réaliser une numération avant chaque cycle et pendant le nadir ; différer ou modifier le protocole en cas de myélosuppression. Les infections et hémorragies peuvent être graves ou mortelles. — CIMA/AEMPS, ficha técnica 86548
- Assurer hydratation et diurèse et utiliser le mesna lorsque le protocole l’exige pour réduire la cystite hémorragique ; surveiller les risques cardiaques, pulmonaires, hépatiques, rénaux et de tumeurs secondaires. — CIMA/AEMPS, ficha técnica 86548
Interactions médicamenteuses
- SévèreVaccins vivants
Mécanisme: L’immunosuppression peut provoquer une infection vaccinale disséminée.
Recommandation: Ils ne sont pas recommandés pendant l’immunosuppression ; planifier la vaccination avec l’équipe soignante.
CIMA/AEMPS, ficha técnica 86548
- SévèreBusulfan ou thiotépa
Mécanisme: Une séquence rapprochée peut augmenter la toxicité ; le busulfan et le thiotépa modifient l’activation/l’élimination du cyclophosphamide.
Recommandation: Espacer le cyclophosphamide de plus de 24 heures après la dernière dose de busulfan et respecter la séquence du protocole avec le thiotépa.
CIMA/AEMPS, ficha técnica 86548
- SévèreModulateurs du CYP et des protéases
Mécanisme: Ils peuvent modifier la bioactivation et l’exposition au cyclophosphamide, ainsi que son efficacité et sa toxicité.
Recommandation: Éviter les associations non nécessaires et n’ajuster que dans le protocole avec surveillance étroite.
CIMA/AEMPS, ficha técnica 86548
Effets indésirables
Communs (≥1%)
Myélosuppression, nausées, vomissements, alopécie et fièvre
Grossesse et allaitement
Contre-indiqué pendant la grossesse et l’allaitement. Utiliser une contraception pendant le traitement et pendant 12 mois après chez la femme et 6 mois après chez l’homme.
Bibliographie récente (PubMed)
In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival. We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response and event-free survival. Overall survival was a secondary end point. Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. At the data-cutoff date (March 22, 2024), the median follow-up was 75.1 months (range, 65.9 to 84.0). The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002). Adverse events were consistent with the established safety profiles of pembrolizumab and chemotherapy. Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with neoadjuvant chemotherapy alone, in overall survival among patients with early-stage triple-negative breast cancer. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).
In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil. In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause. In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups. Among patients undergoing allogeneic HLA-matched HSCT w
Existing guidelines for systemic lupus erythematosus (SLE) predominantly focus on common and major organ involvements. An international taskforce involving experts from three SLE expert groups (ie, the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, the Systemic Lupus Erythematosus International Collaborating Clinics group, and the European Lupus Society) was established. A total of 119 participants contributed to the development of consensus therapeutic strategies for 24 rare SLE manifestations, using a multistep process. For SLE enteritis and pancreatitis, experts recommended hydroxychloroquine, glucocorticoids, and cyclophosphamide or mycophenolate mofetil. Rare lung conditions such as pneumonitis were also managed with cyclophosphamide if severe or with mycophenolate mofetil if not severe. SLE for myocarditis with hydroxychloroquine, glucocorticoids, and cyclophosphamide or mycophenolate mofetil, are recommended based on severity. For CNS manifestations, hydroxychloroquine, glucocorticoids, and cyclophosphamide or mycophenolate mofetil were common choices for treatment. For rare skin manifestations, the preferred strategy was a combination of hydroxychloroquine and glucocorticoids with anifrolumab or mycophenolate mofetil. This expert-based consensus provides a valuable framework for guiding therapeutic decisions where the available recommendations might be insufficient or inapplicable. Cyclophosphamide appears in milk in potentially toxic amounts; additionally, highly toxic active metabolites could add to the risk to the infant. Neutropenia has been reported in 2 infants whose mothers breastfed them while receiving cyclophosphamide. Most sources consider breastfeeding to be contraindicated during maternal cytotoxic antineoplastic drug therapy, especially alkylating agents such as cyclophosphamide.[1] Although some authors have suggested withholding breastfeeding for 1 to 3 days after a dose,[2] the manufacturer rec
Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cancers. The combination of a calcineurin inhibitor and an antimetabolite remains standard care for graft-versus-host disease (GVHD) prophylaxis in these patients. Data from two randomized trials have suggested that post-transplantation cyclophosphamide can reduce the risk of GVHD after SCT from a matched donor when it is added to or replaces the antimetabolite. However, the effects of post-transplantation cyclophosphamide specifically after SCT from a matched related donor remain uncertain, and effects in the context of myeloablative conditioning are unclear. We randomly assigned adults who were undergoing SCT from a matched related donor after myeloablative or reduced-intensity conditioning to receive either post-transplantation cyclophosphamide-cyclosporin (experimental prophylaxis) or cyclosporin-methotrexate (standard prophylaxis). The primary end point was GVHD-free, relapse-free survival. Among 134 patients who underwent randomization, 66 were assigned to receive experimental prophylaxis and 68 to receive standard prophylaxis. GVHD-free, relapse-free survival was significantly longer with experimental prophylaxis (median, 26.2 months; 95% confidence interval [CI], 9.1 to not reached) than with standard prophylaxis (median, 6.4 months; 95% CI, 5.6 to 8.3; P<0.001 by a log-rank test). GVHD-free, relapse-free survival at 3 years was 49% (95% CI, 36 to 61) with experimental prophylaxis and 14% (95% CI, 6 to 25) with standard prophylaxis (hazard ratio for GVHD, relapse, or death, 0.42; 95% CI, 0.27 to 0.66). The cumulative incidence of grade III to IV acute GVHD at 3 months was 3% (95% CI, 1 to 10) in the experimental-prophylaxis group and 10% (95% CI, 4 to 19) in the standard-prophylaxis group. At 2 years, overall survival was 83% and 71%, respectively (hazard ratio for deat