Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/radioterapia , Neoplasias Endometriales/radioterapia , Linfangioma/tratamiento farmacológico , Sirolimus/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias de la Vulva/tratamiento farmacológico , Administración Cutánea , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Femenino , Humanos , Linfangioma/etiología , Persona de Mediana Edad , Radioterapia/efectos adversos , Sirolimus/administración & dosificación , Neoplasias Cutáneas/etiología , Pared Torácica , Neoplasias de la Vulva/etiologíaRESUMEN
Managing extracranial arteriovenous malformations is challenging. Sirolimus (rapamycin) is increasingly being used when surgery and embolization are not advised. Because of its anti-angiogenic properties here we report all extracranial arteriovenous malformation cases treated with sirolimus in 2 French tertiary centers for vascular anomalies. The outcomes were efficacy (complete, partial, no response) based on arteriovenous malformation volume and necrosis/hemorrhage and side effects. We retrospectively included 10 patients (7 children). The sirolimus dose ranged from 0.6 to 3.5 mg/m2. Median (interquartile range [IQR]) treatment time was 24.5 (4.5; 35) months. Five patients showed no response and 5 showed partial response at a median (IQR) of 3 (1; 5) months followed in 2 cases by therapeutic resistance (i.e., progressive disease after 9 and 24 months of treatment). The most frequent side effect was mouth ulcers. This study shows poor efficacy of sirolimus for treating extracranial arteriovenous malformations.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Malformaciones Arteriovenosas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Tacrolimus/uso terapéutico , Adolescente , Adulto , Inhibidores de la Angiogénesis/efectos adversos , Malformaciones Arteriovenosas/diagnóstico por imagen , Niño , Preescolar , Progresión de la Enfermedad , Resistencia a Medicamentos , Francia , Humanos , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Inducción de Remisión , Estudios Retrospectivos , Tacrolimus/efectos adversos , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
BACKGROUND: New targeted melanoma therapies such as B-RAF inhibitors have shown high and promising clinical benefit but have cutaneous side-effects, including photosensitivity, which is triggered in the UVA radiation spectrum. However, visible spectrum implication has not yet been investigated. We conducted a study to determine whether visible light also contributes to the phototoxicity action spectrum of vemurafenib. The secondary end points were to determine the time to complete regression of the phototoxicity post-vemurafenib discontinuation and whether there was a significant difference between the UVA radiation immediate reactivity cut-offs, in patients treated with vemurafenib vs. those treated with dabrafenib. METHOD: This prospective, observational study included patients with B-RAF mutant metastatic melanoma: 34 patients treated with vemurafenib and 9 with dabrafenib. RESULTS: The visible-light phototest results in patients treated with vemurafenib were all negative before and after 2 months of treatment. The UVA radiation phototests conducted 1 or 2 weeks post-vemurafenib discontinuation in 4 patients showed a normalised UVA-radiation reactivity cut-off. UVA radiation phototests after 2 months of treatment were conducted for all patients. The UVA radiation reactivity cut-off had been lowered for 30 patients (88%) on vemurafenib and 3 patients (33%) on dabrafenib. The median UVA radiation reactivity cut-off was 12 J/cm(2) for the patients on vemurafenib and 20 J/cm(2) for the patients on dabrafenib. CONCLUSION: B-RAF inhibitor phototoxicity is exclusively triggered by UVA radiation and resolves rapidly post-treatment discontinuation. A significant difference between the UVA immediate reactivity cut-offs, vemurafenib vs. dabrafenib, explains the difference in the clinical photosensitivity rates reported in the clinical trials.