doxorubicin
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Leucemias, linfomas, sarcomas y tumores sólidos aprobados, sola o en combinaciones oncológicas autorizadas. No corresponde a doxorrubicina liposomal pegilada.
Contraindicaciones
Absolutas
- Insuficiencia miocárdica grave; infarto de miocardio en las 4–6 semanas previas; mielosupresión grave persistente inducida por fármacos; insuficiencia hepática grave (Child-Pugh C o bilirrubina >5 mg/dl); hipersensibilidad grave a doxorrubicina.
Advertencias clínicas
- Controla el hemograma antes de cada ciclo y durante el nadir. No administres fuera de un protocolo oncológico especializado; la mielosupresión puede causar infección o hemorragia mortal. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Calcula la exposición acumulada previa a antraciclinas y evalúa la función ventricular antes y durante el tratamiento. La cardiomiopatía e insuficiencia cardiaca pueden aparecer durante el tratamiento o años después. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Administra solo por una vía intravenosa permeable. Detén inmediatamente ante sospecha de extravasación: es vesicante y puede causar necrosis grave. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Puede causar leucemia secundaria, necrosis tisular grave y síndrome de lisis tumoral. La orina puede volverse roja transitoriamente. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Extravasación: detén, aspira sin retirar la aguja, no laves ni presiones, eleva y aplica hielo 15 minutos cuatro veces al día durante 3 días. Administra dexrazoxano lo antes posible y dentro de 6 horas si está indicado. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Vigila síndrome de lisis tumoral: tras iniciar, controla ácido úrico, potasio, calcio, fosfato y creatinina; la hidratación, alcalinización urinaria y profilaxis con alopurinol pueden reducir complicaciones según el protocolo. La doxorrubicina puede aumentar la toxicidad por radiación y causar reacción de recuerdo. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
Interacciones medicamentosas
- SeveraInhibidores/inductores CYP3A4, CYP2D6 o P-gp
Mecanismo: Pueden aumentar o reducir la exposición a doxorrubicina.
Recomendación: Evita la combinación con moduladores CYP3A4, CYP2D6 o P-gp. Administra doxorrubicina antes de paclitaxel. Evita doxorrubicina concomitante con trastuzumab y, si es posible, durante 7 meses después de suspender trastuzumab; si se usa antes, vigila estrechamente la función cardiaca. Vigila hepatotoxicidad con 6-mercaptopurina.
OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
Embarazo y lactancia
Puede causar daño fetal e infertilidad. Las mujeres deben usar anticoncepción durante y 6 meses después; los hombres durante y 3 meses después, y un preservativo durante y 10 días después si su pareja está embarazada. No amamantes durante ni 10 días después.
Bibliografía reciente (PubMed)
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
The addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma. We conducted a phase 3 trial involving patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously. Patients were randomly assigned to receive either single-agent doxorubicin (six cycles) or doxorubicin plus trabectedin (six cycles), with continued trabectedin as maintenance therapy in patients in the doxorubicin-trabectedin group who did not have disease progression. Surgery to resect residual disease was allowed in each group after six cycles of therapy. Analyses of progression-free survival (primary end point) and overall survival (secondary end point) were adjusted for two stratification factors: tumor origin site (uterine vs. soft tissue) and disease stage (locally advanced vs. metastatic). The primary end-point results were reported previously. A total of 150 patients underwent randomization. At a median follow-up of 55 months (interquartile range, 49 to 63), a total of 107 patients had died (47 in the doxorubicin-trabectedin group and 60 in the doxorubicin group). The median overall survival was longer in the doxorubicin-trabectedin group (33 months; 95% confidence interval [CI], 26 to 48) than in the doxorubicin group (24 months; 95% CI, 19 to 31); the adjusted hazard ratio for death was 0.65 (95% CI, 0.44 to 0.95). In a finding consistent with earlier reports, progression-free survival was longer in the doxorubicin-trabectedin group (12 months; 95% CI, 10 to 16) than in the doxorubicin group (6 months; 95% CI, 4 to 7); the adjusted hazard ratio for progression or death was 0.37 (95% CI, 0.26 to 0.53). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabectedin than with doxorubicin alone. Combination therapy with doxorubicin and trabectedin induction, follo
Anthracyclines, such as doxorubicin, are effective chemotherapeutic agents for the treatment of cancer, but their clinical use is associated with severe and potentially life-threatening cardiotoxicity. Despite decades of research, treatment options remain limited. The mitochondria is commonly considered to be the main target of doxorubicin and mitochondrial dysfunction is the hallmark of doxorubicin-induced cardiotoxicity. Here, we review the pathogenic mechanisms of doxorubicin-induced cardiotoxicity and present an update on cardioprotective strategies for this disorder. Specifically, we focus on strategies that can protect the mitochondria and cover different therapeutic modalities encompassing small molecules, post-transcriptional regulators, and mitochondrial transfer. We also discuss the shortcomings of existing models of doxorubicin-induced cardiotoxicity and explore advances in the use of human pluripotent stem cell derived cardiomyocytes as a platform to facilitate the identification of novel treatments against this disorder.
Metastatic leiomyosarcomas have a poor prognosis, and currently doxorubicin alone is used as the standard first-line treatment. Doxorubicin combined with trabectedin has shown promising results in phase 1 and 2 studies. We aimed to identify and compare the progression-free survival of patients with metastatic or unresectable uterine or soft tissue leiomyosarcoma treated with doxorubicin and trabectedin combined as first-line therapy versus doxorubicin alone in a phase 3 trial. LMS-04 was a randomised, multicentre, open-label, superiority phase 3 trial, which included patients from 20 centres of the French Sarcoma Group (anticancer centers or hospitals with an oncological unit) in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-1, and had metastatic or relapsed unresectable leiomyosarcomas that had not previously been treated with chemotherapy. Patients were randomly assigned (1:1), by means of an interactive web response system (permuted blocks of different sizes from two to six), to receive either intravenous doxorubicin alone (75 mg/m2) once every 3 weeks for up to six cycles or of intravenous doxorubicin (60 mg/m2) plus intravenous trabectedin (1·1 mg/m2) once every 3 weeks up to six cycles followed by maintenance with trabectedin alone. Surgery for residual disease was allowed in both groups after six cycles of treatment. Randomisation was stratified by tumour location (uterine vs soft tissue) and disease (locally advanced vs metastatic). The primary endpoint was progression-free survival assessed by blinded independent central review and according to Response Evaluation Criteria in Solid Tumours 1.1 criteria. Efficacy analyses were performed on all randomly assigned patients, based on the intention-to-treat principle. The safety population included all randomly assigned patients who received at least one cycle of treatment. This trial is registered with ClinicalTrials.gov, NCT02997358, and
In the POLARIX study (ClinicalTrials.gov identifier: NCT03274492), polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) showed a significant progression-free survival (PFS) benefit versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated intermediate- or high-risk diffuse large B-cell lymphoma (DLBCL; median follow-up: 28 months). In this 5-year update, sustained PFS benefits favoring Pola-R-CHP were observed. In the global intention-to-treat population (N = 879; median follow-up: 64.1 months), Pola-R-CHP demonstrated a significant PFS benefit over R-CHOP (hazard ratio [HR], 0.77 [95% CI, 0.62 to 0.97]), with 5-year PFS rates of 64.9% (95% CI, 59.8 to 70.0) and 59.1% (95% CI, 53.9 to 64.3), respectively. Although not statistically significant, overall survival analysis showed a HR of 0.85 (95% CI, 0.63 to 1.15) at the 5-year data cut compared with 0.94 (95% CI, 0.67 to 1.33) at the 2-year data cut. In the expanded population, 46 and 62 patients had lymphoma-related deaths in the Pola-R-CHP and R-CHOP arms, respectively. Exploratory analyses showed favorable 5-year survival rates with Pola-R-CHP in high-risk subgroups, including activated B-cell DLBCL and International Prognostic Index score 3-5. Long-term tolerability was similar between treatment arms. Findings confirm Pola-R-CHP represents a standard of care for frontline treatment of DLBCL.