bleomycin
Regulatory sources consulted
Approved indications
- Squamous-cell carcinomas, lymphomas, testicular cancer, and malignant pleural effusion, in authorized regimens.
Contraindications
Absolute
- Hypersensitivity or idiosyncratic reaction to bleomycin; acute lung infection or severe lung damage; ataxia-telangiectasia; breastfeeding.
Clinical warnings
- Pulmonary toxicity may be fatal and occur even below 400 units; risk rises with cumulative dose, age, renal impairment, chest radiation, and oxygen. Monitor symptoms, imaging, and pulmonary function for 8 weeks afterward and discontinue for lung injury. — CIMA/AEMPS, ficha técnica 49313
- During surgery, use the lowest FiO2 compatible with adequate oxygenation and avoid fluid overload. In lymphoma, follow the protocol test dose and observation for idiosyncratic reactions. — CIMA/AEMPS, ficha técnica 49313
Drug interactions
- HighOxygen, cisplatin, and other pneumotoxic agents
Mechanism: Oxygen and other pneumotoxic agents increase lung injury; cisplatin may reduce renal clearance.
Recommendation: Minimize supplemental oxygen, monitor renal and pulmonary function, and use only protocol-defined combinations.
CIMA/AEMPS, ficha técnica 49313
Pregnancy and lactation
It may cause fetal harm. Avoid pregnancy; women and men must use contraception during treatment and for 3 months afterward. Breastfeeding is contraindicated.
Recent literature (PubMed)
Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities currently available. The aim of this study was to conduct an evidence-based review of all prospective data regarding keloid treatments published between 2010 and 2020. A systematic literature search of PubMed (National Library of Medicine), Embase (Elsevier), and Cochrane Library (Wiley) was performed in November of 2020. Search strategies with the keywords "keloid" and "treatment" were performed by a medical librarian. The search was limited to prospective studies that were peer-reviewed, reported on clinical outcomes of keloid therapies, and were published in the English language between January 1, 2010, and November 24, 2020. A total of 3462 unique citations were identified, of which 108 studies met inclusion criteria. Current literature supports silicone gel or sheeting with corticosteroid injections as first-line therapy for keloids. Adjuvant intralesional 5-fluorouracil (5-FU), bleomycin, or verapamil can be considered, although mixed results have been reported with each. Laser therapy can be used in combination with intralesional corticosteroids or topical steroids with occlusion to improve drug penetration. Excision of keloids with immediate post-excision radiation therapy is an effective option for recalcitrant lesions. Finally, silicone sheeting and pressure therapy have evidence for reducing keloid recurrence. This review was limited by heterogeneity of subject characteristics and study outcome measures, small sample sizes, and inconsistent study designs. Larger and more robust controlled studies are necessary to further understand the variety of existing and emerging keloid treatments, including corticosteroids, cryotherapy, intralesional injections, lasers, photodynamic therapy, excision and radiation, pressure dressings, and others.
Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are recognized as a promising strategy for cell-free therapy, however, their therapeutic role in pulmonary fibrosis remains unrevealed. Here, we report the safety and efficacy of MSC-EVs from human umbilical cord (hUCMSC-EVs) evaluated in mouse models and pulmonary fibrosis patients. We established a rigorous system to produce high-quality of hUCMSC-EVs, characterized by miRNA, protein, and metabolite profiles. When administered via nebulization, hUCMSC-EVs predominantly accumulated in murine lungs and ameliorated bleomycin-induced pulmonary fibrosis, with increased survival rate (from 20% to 80%), restored lung volume, and attenuated injury severity accompanied by elevated oxyhemoglobin saturation and improved pulmonary function evaluations. We performed a phase l clinical trial involving twenty-four patients in a randomized, single-blind, and placebo-controlled study to treat pulmonary fibrosis (MR-46-22-004531, ChiCTR2300075466). All participants tolerated the nebulized hUCMSC-EVs well, with no serious adverse events. Patients receiving the combined therapy of nebulized hUCMSC-EVs and routine treatment demonstrated significant improvements in both lung function indices (forced vital capacity and maximal voluntary ventilation) and respiratory health status (as measured by the Saint George's Respiratory Questionnaire and Leicester Cough Questionnaire. Overall, patients upon the additional therapy with nebulized hUCMSC-EVs gained significant benefits compared with those accepted only routine treatment. Remarkably, two patients with advanced post-inflammatory pulmonary fibrosis exhibited clinically significant regression on serial CT scans after hUCMSC-EVs therapy. These findings suggest that nebulized hUCMSC-EVs could be used as a promising therapeutic strategy for treating pulmonary fibrosis diseases.
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
Drug-induced interstitial lung disease (DIILD) is a form of interstitial lung disease resulting from exposure to drugs causing inflammation and possibly interstitial fibrosis. Antineoplastic drugs are the primary cause of DIILD, accounting for 23%-51% of cases, with bleomycin, everolimus, erlotinib, trastuzumab-deruxtecan and immune checkpoint inhibitors being the most common causative agents. DIILD can be difficult to identify and manage, and there are currently no specific guidelines on the diagnosis and treatment of DIILD caused by anticancer drugs. To develop recommendations for the diagnosis and management of DIILD in cancer patients. Based on the published literature and their clinical expertise, a multidisciplinary group of experts in Italy developed recommendations stratified by DIILD severity, based on the Common Terminology Criteria for Adverse Events. The recommendations highlight the importance of multidisciplinary interaction in the diagnosis and management of DIILD. Important components of the diagnostic process are physical examination and careful patient history-taking, measurement of vital signs (particularly respiratory rate and arterial oxygen saturation), relevant laboratory tests, respiratory function testing with spirometry and diffusing capacity of the lung for carbon monoxide and computed tomography/imaging. Because the clinical and radiological signs of DIILD are often similar to those of pneumonias or interstitial lung diseases, differential diagnosis is important, including microbial and serological testing to exclude or confirm infectious causes. In most cases, management of DIILD requires the discontinuation of the antineoplastic agent and the administration of short-term steroids. Steroid tapering must be undertaken slowly to prevent reactivation of DIILD. Patients with severe and very severe (grade 3 and 4) DIILD will require hospitalisation and often need oxygen and non-invasive ventilation. Decisions about invasive ventilation should
In adults with advanced-stage Hodgkin's lymphoma, the CD30-directed antibody-drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin's lymphoma is unclear. We conducted an open-label, multicenter, randomized, phase 3 trial involving patients 2 to 21 years of age with previously untreated Hodgkin's lymphoma of stage IIB with bulk tumor or stage IIIB, IVA, or IVB. Patients were assigned to receive five 21-day cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (brentuximab vedotin group) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group). Slow-responding lesions, defined by a score of 4 or 5 (on a 5-point scale, with scores of 1 to 3 indicating rapid-responding lesions), were identified on centrally reviewed positron-emission tomography-computed tomography after two cycles. Involved-site radiation therapy was administered after the fifth cycle of therapy to slow-responding lesions and to large mediastinal adenopathy that was present at diagnosis. The primary end point was event-free survival, defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Safety and overall survival were assessed. Of 600 patients who were enrolled across 153 institutions, 587 were eligible. At a median follow-up of 42.1 months (range, 0.1 to 80.9), the 3-year event-free survival was 92.1% (95% confidence interval [CI], 88.4 to 94.7) in the brentuximab vedotin group, as compared with 82.5% (95% CI, 77.4 to 86.5) in the standard-care group (hazard ratio for event or death, 0.41; 95% CI, 0.25 to 0.67; P<0.001). The percentage of patients who received involved-site radiation therapy d