RESUMEN
INTRODUCTION: Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin's lymphoma (NHL) receiving anthracycline-based chemotherapy. METHODS AND ANALYSIS: PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects. ETHICS AND DISSEMINATION: A favourable opinion was given following research ethics committee review by West Midlands-Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03265574.
Asunto(s)
Neoplasias de la Mama , Linfoma no Hodgkin , Linfoma , Adulto , Humanos , Femenino , Neoplasias de la Mama/patología , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Estudios Prospectivos , Enalapril/uso terapéutico , Antibióticos Antineoplásicos/efectos adversos , Antraciclinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Cutaneous recurrence from breast cancer can pose a clinical challenge. It might be the only disease site, or could be part of disseminated disease, and often profoundly affects quality of life. Electrochemotherapy is a palliative treatment using electric pulses to locally permeabilize tumor cells and thereby significantly increase bleomycin cytotoxicity. Collaborating with the International Network for Sharing Practice on ElectroChemoTherapy (INSPECT), we consecutively and prospectively accrued data on patients treated with electrochemotherapy for cutaneous metastases from breast cancer. PATIENTS AND METHODS: Patients were treated with electrochemotherapy at 10 European centers. Under either local or general anaesthesia patients were treated with either local injection (1000 IU/mL intratumoral) or systemic infusion (15,000 IU/m2) of bleomycin. RESULTS: One hundred nineteen patients were included at 10 institutions in the INSPECT network. The primary location was the chest (89%), the median diameter of the cutaneous metastases was 25 mm. Ninety patients were available for response evaluation after 2 months. Complete response was observed in 45 patients (50%), partial response in 19 (21%), stable disease in 16 (18%), and progressive disease in 7 (8%). Three patients were not evaluable. Common side effects were ulceration, long-lasting hyperpigmentation, and low-grade pain. No serious adverse events were observed. CONCLUSION: Electrochemotherapy showed high response rates after a single treatment. Electrochemotherapy has few side effects and can be used as an adjunct to systemic therapies or as a solo treatment. We therefore recommend considering electrochemotherapy for patients with cutaneous metastases.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Bleomicina/uso terapéutico , Neoplasias de la Mama/patología , Electroquimioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Neoplasias de la Mama/terapia , Bases de Datos Factuales , Electroquimioterapia/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Electrochemotherapy describes the use of electric pulses to enhance chemotherapy uptake, and has proven highly efficient in treating cutaneous metastases. Patients referred for electrochemotherapy present with diverse clinical pictures, from multiple small lesions to large, ulcerated lesions. Post-electrochemotherapy pain has been observed in some patients. The objectives of this study were to evaluate pain scores before and after electrochemotherapy, and to investigate if patients at risk of post-procedure pain could be identified. METHODS: Seven cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively reported to a common database. Electrochemotherapy consisted of intratumoural or intravenous injection of bleomycin, followed by delivery of electric pulses in local or general anesthesia. RESULTS: Of 121 patients 39% had metastatic melanoma, 18% squamous cell carcinoma, 16% breast cancer, 13% basal-cell carcinoma, and 14% other malignancies. Median size of the largest nodules was 2.3 cm (range 0.3-40 cm). A majority of patients presented with low pain scores, and this continued through follow-up (74%). A subset of patients had moderate (13%) or severe pain (13%) after treatment. Post-procedure pain was statistically significantly associated with: 1) moderate or severe pain before treatment (p<0.0001); 2) size of the largest treated lesion (p<0.01); 3) previous irradiation (p<0.02); and 4) high treatment current value (p<0.0001). CONCLUSION: The majority of patients had no or mild pain after electrochemotherapy. Patients at risk for post-procedure pain could be identified at the pre-treatment visit, and/or at the time of treatment, enabling a pain management strategy for this group.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Bleomicina/administración & dosificación , Electroquimioterapia/efectos adversos , Neoplasias/tratamiento farmacológico , Dolor/etiología , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Anestesia General , Anestesia Local , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Distribución de Chi-Cuadrado , Bases de Datos Factuales , Electroquimioterapia/métodos , Femenino , Humanos , Inyecciones Intralesiones/métodos , Inyecciones Intravenosas/métodos , Masculino , Melanoma/tratamiento farmacológico , Melanoma/secundario , Persona de Mediana Edad , Neoplasias/patología , Dimensión del Dolor/métodos , Medición de Riesgo/métodos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundario , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: Cutaneous metastases may cause considerable discomfort as a consequence of ulceration, oozing, bleeding and pain. Electrochemotherapy has proven to be highly effective in the treatment of cutaneous metastases. Electrochemotherapy utilises pulses of electricity to increase the permeability of the cell membrane and thereby augment the effect of chemotherapy. For the drug bleomycin, the effect is enhanced several hundred-fold, enabling once-only treatment. The primary endpoint of this study is to evaluate the efficacy of electrochemotherapy as a palliative treatment. METHODS: This phase II study is a collaboration between two centres, one in Denmark and the other in the UK. Patients with cutaneous metastases of any histology were included. Bleomycin was administered intratumourally or intravenously followed by application of electric pulses to the tumour site. RESULTS: Fifty-two patients were included. Complete and partial response rate was 68% and 18%, respectively, for cutaneous metastases <3 cm and 8% and 23%, respectively, for cutaneous metastases >3 cm. Treatment was well-tolerated by patients, including the elderly, and no serious adverse events were observed. CONCLUSIONS: ECT is an efficient and safe treatment and clinicians should not hesitate to use it even in the elderly.