carmustine
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Tratamiento especializado de tumores cerebrales, mieloma múltiple, enfermedad de Hodgkin y linfomas no Hodgkin en regímenes aprobados.
Contraindicaciones
Absolutas
- Hipersensibilidad; mielodepresión grave; insuficiencia renal terminal; menores de 18 años; lactancia.
Advertencias clínicas
- Controla hemograma cada semana durante al menos 6 semanas. No repitas hasta plaquetas >100.000/mm³ y leucocitos >4000/mm³. — CIMA/AEMPS, ficha técnica 89646
- Realiza función pulmonar basal y seguimiento; vigila fibrosis pulmonar acumulativa, toxicidad renal/hepática y extravasación. — CIMA/AEMPS, ficha técnica 89646
Interacciones medicamentosas
- SeveraCimetidina
Mecanismo: Puede aumentar la toxicidad medular retardada grave.
Recomendación: Evita la combinación.
CIMA/AEMPS, ficha técnica 89646
- SeveraDigoxina, antiepilépticos o melfalán
Mecanismo: Puede disminuir la absorción de digoxina/antiepilépticos o aumentar toxicidad pulmonar con melfalán.
Recomendación: Monitoriza efecto o niveles; evita melfalán si el protocolo no justifica la combinación.
CIMA/AEMPS, ficha técnica 89646
Eventos adversos
Comunes (≥1%)
Mielosupresión, anemia, ataxia, mareo, cefalea, náuseas, vómitos, flebitis, toxicidad pulmonar, neumonitis, anorexia, estreñimiento, diarrea, estomatitis, alopecia y reacción en el lugar de inyección
Embarazo y lactancia
Puede causar daño fetal e infertilidad. Usa anticoncepción durante el tratamiento y durante 6 meses después en mujeres y hombres. No amamantes durante el tratamiento ni durante 7 días 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.
219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.
Although it is evident that standard-dose whole-brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the US Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with nonmyeloablative consolidation after induction therapy for PCNSL. To our knowledge, this is the first randomized trial to be initiated that eliminates whole-brain radiotherapy as a consolidative approach in newly diagnosed PCNSL. Patients aged 18 to 75 years were randomly assigned in a 1:1 manner to induction therapy (methotrexate, temozolomide, rituximab, and cytarabine) followed by consolidation with either thiotepa plus carmustine and autologous stem cell rescue vs induction followed by nonmyeloablative, infusional etoposide plus cytarabine. The primary end point was progression-free survival (PFS). A total of 113 patients were randomized, and 108 (54 in each arm) were evaluable. More patients in the nonmyeloablative arm experienced progressive disease or death during induction (28% vs 11%; P = .05). Thirty-six patients received autologous stem cell transplant, and 34 received nonmyeloablative consolidation. The estimated 2-year PFS was higher in the myeloablative vs nonmyeloablative arm (73% vs 51%; P = .02). However, a planned secondary analysis, landmarked at start of the consolidation, revealed that the estimated 2-year PFS in those who completed consolidation therapy was not significantly different between the arms (86% vs 71%; P = .21). Both consolidative strategies yielded encouraging efficacy and similar toxicity profiles. This trial was registered at www.clininicals.gov as #NCT01511562.
This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, and cyclophosphamide in doses of > 1500 mg/m2 and the combination of cyclophosphamide and an anthracycline (AC) in women with breast cancer. A systematic review report following the PRISMA guidelines of the literature from January 1, 2015, until February 1, 2023, was performed. PubMed (Ovid), Scopus (Google), and the Cochrane Database of Systematic Reviews were searched. The literature search was limited to randomized controlled trials, systematic reviews, and meta-analyses. Forty-six new references were determined to be relevant. The main topics identified were (1) steroid-sparing regimens, (2) olanzapine-containing regimens, and (3) other issues such as comparisons of antiemetics of the same drug class, intravenous NK1 receptor antagonists, and potentially new antiemetics. Five updated recommendations are presented. There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC. Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC. No major differences between 5-HT3 receptor antagonists or between NK1 receptor antagonists were identified. No new antiemetic agents qualified for inclusion in the updated recommendations.