RESUMEN
Amid controversial reports that COVID-19 can be treated with a combination of the antimalarial drug hydroxychloroquine (HCQ) and the antibiotic azithromycin (AZI), a clinical trial (ONCOCOVID, NCT04341207) was launched at Gustave Roussy Cancer Campus to investigate the utility of this combination therapy in cancer patients. In this preclinical study, we investigated whether the combination of HCQ+AZI would be compatible with the therapeutic induction of anticancer immune responses. For this, we used doses of HCQ and AZI that affect whole-body physiology (as indicated by a partial blockade in cardiac and hepatic autophagic flux for HCQ and a reduction in body weight for AZI), showing that their combined administration did not interfere with tumor growth control induced by the immunogenic cell death inducer oxaliplatin. Moreover, the HCQ+AZI combination did not affect the capacity of a curative regimen (cisplatin + crizotinib + PD-1 blockade) to eradicate established orthotopic lung cancers in mice. In conclusion, it appears that HCQ+AZI does not interfere with the therapeutic induction of therapeutic anticancer immune responses.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Azitromicina/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Hidroxicloroquina/administración & dosificación , Neoplasias/tratamiento farmacológico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Azitromicina/farmacocinética , COVID-19/inmunología , COVID-19/virología , Línea Celular Tumoral , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Ensayos Clínicos Fase II como Asunto , Crizotinib/administración & dosificación , Crizotinib/farmacocinética , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Quimioterapia Combinada/métodos , Femenino , Francia , Humanos , Hidroxicloroquina/farmacocinética , Ratones , Neoplasias/inmunología , Oxaliplatino/administración & dosificación , Oxaliplatino/farmacocinética , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations, even if data for this population are still scarce. They may have to evolve according to the rapid evolution of knowledge on COVID-19.