erlotinib
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Cáncer de pulmón no microcítico metastásico con deleción del exón 19 de EGFR o mutación L858R del exón 21, como primera línea, mantenimiento o tras progresión; no junto con quimioterapia basada en platino. Cáncer de páncreas localmente avanzado irresecable o metastásico solo en combinación con gemcitabina.
Contraindicaciones
Absolutas
- CIMA: hipersensibilidad al principio activo o excipientes; la etiqueta FDA no establece contraindicaciones formales.
Advertencias clínicas
- Ante síntomas pulmonares nuevos o peores, interrumpe e investiga; suspende definitivamente si se confirma EPI. Vigila hígado, riñón, electrolitos, diarrea, piel y ojos. — OpenFDA, set_id 2c4c7353-b81c-4651-8aac-6d15e88145af
- Con gemcitabina puede causar microangiopatía trombótica. Suspende definitivamente ante perforación gastrointestinal o toxicidad cutánea ampollosa grave. — OpenFDA, set_id 2c4c7353-b81c-4651-8aac-6d15e88145af
Interacciones medicamentosas
- SeveraModuladores CYP3A y tabaquismo
Mecanismo: Los inhibidores aumentan y los inductores o el tabaco reducen la exposición.
Recomendación: Evita cuando sea posible. Con inhibidor reduce en pasos de 50 mg; con inductor aumenta 50 mg cada 2 semanas hasta 450 mg; en fumadores puede requerirse hasta 300 mg y vuelve a la dosis previa al dejar de fumar.
OpenFDA, set_id 2c4c7353-b81c-4651-8aac-6d15e88145af
- SeveraSupresores del ácido gástrico
Mecanismo: Reducen la absorción de erlotinib.
Recomendación: Evita IBP. Administra erlotinib 10 horas después y al menos 2 horas antes del siguiente antagonista H2.
OpenFDA, set_id 2c4c7353-b81c-4651-8aac-6d15e88145af
- SeveraWarfarina o cumarínicos
Mecanismo: Pueden aumentar INR y hemorragia.
Recomendación: Controla INR regularmente.
OpenFDA, set_id 2c4c7353-b81c-4651-8aac-6d15e88145af
Eventos adversos
Comunes (≥1%)
exantema · diarrea · pérdida de apetito · fatiga · náuseas · vómitos
Embarazo y lactancia
Puede causar daño fetal. Las mujeres deben usar anticoncepción durante el tratamiento y 1 mes después. No amamantes durante ni 2 semanas después.
Bibliografía reciente (PubMed)
Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.
To evaluate the risk of cardiovascular adverse events associated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Systematic review and network meta-analysis. PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and three clinical trial registries, from inception to 20 November 2024. Randomised controlled trials comparing EGFR tyrosine kinase inhibitor monotherapy with placebo or other treatments in patients with EGFR-mutated NSCLC. Pairs of reviewers extracted data and assessed risk of bias. A random effects network meta-analysis using a frequentist approach compared adverse drug reactions across different treatments. Certainty of evidence was evaluated using the confidence in network meta-analysis approach. Pairwise meta-analyses were done to compare the three generations of EGFR tyrosine kinase inhibitors. The network meta-analysis comprised 89 randomised controlled trials involving 29 813 participants, mean follow-up 2.18 years. Compared with placebo, both first generation (odds ratio 1.51, 95% confidence interval 1.01 to 2.26; high certainty; pooled incidence 3.2%) and third generation EGFR tyrosine kinase inhibitors (2.18, 1.46 to 3.27; high certainty; 9.5%) were associated with increased risks of cardiac adverse events. Among third generation inhibitors, osimertinib (2.53, 1.53 to 4.19; high certainty; 8.9%) and lazertinib (2.84, 1.17 to 6.91; moderate certainty; 2.7%) were associated with cardiac adverse events. Combined therapies, such as antiangiogenesis with erlotinib or gefitinib, were associated with vascular adverse events (high certainty), whereas antiangiogenesis with osimertinib was associated with cardiovascular adverse events (moderate to high certainty). Also, the risk of arrhythmias was significantly higher with third generation inhibitors (3.26, 1.83 to 5.81; high certainty; 7.3%), such as osimertinib alone (3.35, 1.75 to
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
The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively (P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively (P = .744). To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.
Hereditary leiomyomatosis and renal-cell cancer (HLRCC) is an inherited disorder characterized by germline pathogenic variants in the gene encoding fumarate hydratase and an increased risk of papillary renal-cell carcinoma. No effective therapy is known for patients with advanced HLRCC-associated papillary renal-cell carcinoma, and most patients die from progressive disease. In this open-label, phase 2 study, we evaluated the efficacy of bevacizumab (10 mg per kilogram of body weight every 2 weeks) and erlotinib (150 mg once daily) in patients with advanced HLRCC-associated or sporadic papillary renal-cell carcinoma. The primary end point was overall response; secondary end points included progression-free and overall survival. A total of 43 patients with HLRCC-associated papillary renal-cell carcinoma and 40 patients with sporadic papillary renal-cell carcinoma were enrolled. A confirmed response occurred in 31 patients (72%; 95% confidence interval [CI], 57 to 83) with HLRCC-associated papillary renal-cell carcinoma; the median progression-free survival was 21.1 months (95% CI, 15.6 to 26.6), and the median overall survival was 44.6 months (95% CI, 32.7 to could not be estimated). A confirmed response occurred in 14 patients (35%; 95% CI, 22 to 51) with sporadic papillary renal-cell carcinoma, with a median progression-free survival of 8.9 months (95% CI, 5.5 to 18.3) and a median overall survival of 18.2 months (95% CI, 12.6 to 29.3). The most common treatment-related adverse events were acneiform rash (93%), diarrhea (89%), and proteinuria (78%). The most common treatment-related adverse events of grade 3 or higher were hypertension (34%) and proteinuria (17%). The combination of bevacizumab and erlotinib showed antitumor activity in patients with HLRCC-associated or sporadic papillary renal-cell carcinoma. Toxic effects were those known to be associated with this combination. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT011