cyclophosphamide
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Tratamiento oncológico sistémico en regímenes especializados para leucemias, linfomas, mieloma, tumores sólidos y acondicionamiento de trasplante; algunas enfermedades autoinmunes potencialmente mortales.
Contraindicaciones
Absolutas
- Hipersensibilidad a ciclofosfamida o metabolitos; infección aguda; aplasia o depresión medular previa; infección urinaria, toxicidad urotelial aguda u obstrucción urinaria.
- Embarazo o lactancia; menores de 18 años para esta formulación con alcohol; pacientes asiáticos con genotipo ALDH2 mutante.
Advertencias clínicas
- Realiza hemograma antes de cada ciclo y durante el nadir; aplaza o modifica el protocolo ante mielosupresión. Las infecciones y hemorragias pueden ser graves o mortales. — CIMA/AEMPS, ficha técnica 86548
- Asegura hidratación y diuresis, y usa mesna cuando el protocolo lo indique para reducir cistitis hemorrágica; vigila corazón, pulmón, hígado, riñón y neoplasias secundarias. — CIMA/AEMPS, ficha técnica 86548
Interacciones medicamentosas
- SeveraVacunas vivas
Mecanismo: La inmunosupresión puede producir una infección vacunal diseminada.
Recomendación: No se recomiendan durante la inmunosupresión; planifica la vacunación con el equipo tratante.
CIMA/AEMPS, ficha técnica 86548
- SeveraBusulfano o tiotepa
Mecanismo: La secuencia cercana puede aumentar toxicidad; busulfano y tiotepa alteran la activación/eliminación de ciclofosfamida.
Recomendación: Separa ciclofosfamida más de 24 horas de la última dosis de busulfano y respeta la secuencia del protocolo con tiotepa.
CIMA/AEMPS, ficha técnica 86548
- SeveraModuladores CYP y proteasa
Mecanismo: Pueden alterar la bioactivación y la exposición de ciclofosfamida, modificando eficacia y toxicidad.
Recomendación: Evita combinaciones no necesarias y ajusta solo dentro del protocolo con monitorización estrecha.
CIMA/AEMPS, ficha técnica 86548
Eventos adversos
Comunes (≥1%)
Mielosupresión, náuseas, vómitos, alopecia y fiebre
Embarazo y lactancia
Contraindicado durante el embarazo y la lactancia. Usa anticoncepción durante el tratamiento y durante 12 meses después en mujeres y 6 meses después en hombres.
Bibliografía reciente (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