etoposide
Regulatory sources consulted
Approved indications
- Relapsed or refractory testicular tumors; small-cell lung cancer; Hodgkin or non-Hodgkin lymphoma; acute myeloid leukemia; high-risk gestational trophoblastic neoplasia; and non-epithelial ovarian cancer in combination or epithelial ovarian cancer resistant or refractory to platinum, according to the authorized regimen.
Contraindications
Absolute
- Hypersensitivity; breastfeeding; yellow-fever vaccine or live vaccines in immunocompromised patients.
Clinical warnings
- Check platelets, hemoglobin, leukocytes, and differential count before treatment and before every subsequent dose. Delay or modify for myelosuppression; infections and bleeding may be severe or fatal. — CIMA/AEMPS, ficha técnica 63625
- Infuse slowly to reduce hypotension. Monitor anaphylaxis, extravasation, and secondary leukemia. Adjust subsequent doses if neutrophils are <500/mm³ for more than 5 days, fever or infection occurs, platelets are <25,000/mm³ not attributable to the disease, grade 3–4 toxicity occurs, or CrCl is <50 mL/min. — CIMA/AEMPS, ficha técnica 63625
Drug interactions
- HighHigh-concentration cyclosporine
Mechanism: At concentrations >2,000 ng/mL it may increase etoposide AUC by about 80% and reduce clearance by 38%.
Recommendation: Closely monitor exposure and toxicity and individualize management under a specialist protocol.
CIMA/AEMPS, ficha técnica 63625
- HighPhenytoin, enzyme inducers, or warfarin
Mechanism: Inducers may reduce exposure and efficacy; etoposide may increase INR with warfarin.
Recommendation: Monitor efficacy, concentrations when appropriate, and INR; adjust under supervision.
CIMA/AEMPS, ficha técnica 63625
- ModerateLive vaccines
Mechanism: Immunosuppression may cause disseminated vaccine infection.
Recommendation: Do not give live vaccines during immunosuppression.
CIMA/AEMPS, ficha técnica 63625
- HighCisplatin
Mechanism: It may reduce total body clearance of etoposide and increase exposure.
Recommendation: Closely monitor toxicity and exposure and individualize according to protocol.
CIMA/AEMPS, ficha técnica 63625
- HighOther myelosuppressants
Mechanism: Bone-marrow toxicity may be additive or synergistic.
Recommendation: Coordinate the regimen and intensify blood-count monitoring before every dose.
CIMA/AEMPS, ficha técnica 63625
Pregnancy and lactation
It may cause fetal harm and infertility. Women and men must use effective contraception during treatment and for 6 months afterward. Do not breastfeed. Consider sperm preservation before treatment.
Recent literature (PubMed)
Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma with an incidence of 4.7 cases per 100 000 individuals in 2021 in the US and a 5-year overall survival of 12% to 30%. Cigarette smoking is the primary risk factor for development of SCLC, as 95% of patients diagnosed with SCLC have a history of tobacco use. Patients with SCLC may present with respiratory symptoms such as cough (40%), shortness of breath (34%), hemoptysis (10%), or metastases with corresponding local symptoms (30%) such as pleuritis or bone pain; approximately 60% of patients with SCLC may be asymptomatic at diagnosis. Chest imaging may demonstrate central hilar (85%) or mediastinal lymphadenopathy (75%). At diagnosis, approximately 15% of patients have brain metastases, which may present as headache or focal weakness. Diagnosis is confirmed by biopsy of a primary lung mass, thoracic lymph node, or metastatic lesion. Small cell lung cancer is classified into limited stage (LS-SCLC; 30%) vs extensive stage (ES-SCLC; 70%) based on whether the disease can be treated within a radiation field that is typically confined to 1 hemithorax but may include contralateral mediastinal and supraclavicular nodes. For patients with LS-SCLC, surgery or concurrent chemotherapy with platinum-etoposide and radiotherapy is potentially curative in 30% of patients. More recently, median survival for LS-SCLC has reached up to 55.9 months with the addition of durvalumab, an immunotherapy. First-line treatment for ES-SCLC is combined treatment with platinum-etoposide chemotherapy and immunotherapy with the programmed cell death 1 ligand 1 (PD-L1) inhibitors durvalumab or atezolizumab followed by maintenance immunotherapy until disease progression or toxicity. Although initial rates of tumor shrinkage are 60% to 70% with platinum-etoposide and immunotherapy treatment, the median overall survival of patients treated for ES-SCLC is approximately 12 to 13 months, with 60% of patients relapsing within 3 months.
Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide. IMforte was a randomised, open-label, phase 3 trial done at 96 hospitals and medical centres in 13 countries (Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK, and the USA). Eligible patients were aged 18 years or older with treatment-naive ES-SCLC. Patients received four 21-day cycles of induction treatment (atezolizumab, carboplatin, and etoposide). After completing induction treatment, eligible patients without disease progression were randomly assigned (1:1) using permuted blocks (Interactive Voice/Web Response System) to receive maintenance treatment intravenously every 3 weeks with lurbinectedin (3·2 mg/m2; with granulocyte colony-stimulating factor prophylaxis) plus atezolizumab (1200 mg) or atezolizumab (1200 mg). The two primary endpoints were independent review facility-assessed (IRF) progression-free survival and overall survival, measured from randomisation into the maintenance phase. Efficacy endpoints were assessed in the full analysis set, which included all patients who were randomly assigned to maintenance phase treatment, regardless of whether they received their assigned study treatment. Safety was assessed in all patients who received at least one dose of lurbinectedin or atezolizumab, and was analysed according to the treatment received. This study is registered with ClinicalTrials.gov, NCT05091567, and is closed for recruitment. Between Nov 17, 2021, and Jan 11, 2024, 895 patients were screened for enrolment, of whom 660 (74%) were enrolled into the induction phase. Between May 24, 2022,
Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum-etoposide chemotherapy. Patients with metastatic (extensive-stage) disease are treated with a combination of platinum-etoposide chemotherapy plus immunotherapy with an anti-programmed death-ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum-based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development. No information is available on the excretion of cytarabine into breastmilk. However, the drug has a short half-life of 2 to 3 h