doxorubicin
Regulatory sources consulted
Approved indications
- Approved leukemias, lymphomas, sarcomas, and solid tumors, alone or in authorized oncology combinations. This is not pegylated liposomal doxorubicin.
Contraindications
Absolute
- Severe myocardial insufficiency; myocardial infarction within the previous 4–6 weeks; severe persistent drug-induced myelosuppression; severe hepatic impairment (Child-Pugh C or bilirubin >5 mg/dL); severe hypersensitivity to doxorubicin.
Clinical warnings
- Monitor blood counts before each cycle and through the nadir. Do not administer outside a specialist oncology protocol; myelosuppression may cause fatal infection or bleeding. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Calculate prior cumulative anthracycline exposure and assess ventricular function before and during treatment. Cardiomyopathy and heart failure may occur during treatment or years later. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Administer only through a patent intravenous line. Stop immediately if extravasation is suspected: it is a vesicant and may cause severe necrosis. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- It may cause secondary leukemia, severe tissue necrosis, and tumor lysis syndrome. Urine may temporarily turn red. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Extravasation: stop, aspirate without removing the needle, do not flush or apply pressure, elevate, and apply ice for 15 minutes four times daily for 3 days. Give dexrazoxane as soon as possible and within 6 hours when indicated. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
- Monitor tumor lysis syndrome: after starting, check uric acid, potassium, calcium, phosphate, and creatinine; hydration, urinary alkalinization, and allopurinol prophylaxis may reduce complications according to protocol. Doxorubicin may increase radiation toxicity and cause radiation recall. — OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
Drug interactions
- HighCYP3A4, CYP2D6, or P-gp inhibitors/inducers
Mechanism: They may increase or decrease doxorubicin exposure.
Recommendation: Avoid combination with CYP3A4, CYP2D6, or P-gp modulators. Give doxorubicin before paclitaxel. Avoid concomitant doxorubicin with trastuzumab and, if possible, for 7 months after trastuzumab is stopped; if used sooner, closely monitor cardiac function. Monitor hepatotoxicity with 6-mercaptopurine.
OpenFDA, set_id 00634b2b-4e48-4178-8877-28582af894ad
Pregnancy and lactation
It may cause fetal harm and infertility. Women must use contraception during treatment and for 6 months afterward; men during treatment and for 3 months afterward, and condoms during treatment and for 10 days afterward if their partner is pregnant. Do not breastfeed during treatment or for 10 days afterward.
Recent literature (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.