ABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Azithromycin/administration & dosage , COVID-19 Drug Treatment , Hydroxychloroquine/administration & dosage , Neoplasms/drug therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Azithromycin/pharmacokinetics , COVID-19/immunology , COVID-19/virology , Cell Line, Tumor , Cisplatin/administration & dosage , Cisplatin/pharmacokinetics , Clinical Trials, Phase II as Topic , Crizotinib/administration & dosage , Crizotinib/pharmacokinetics , Disease Models, Animal , Drug Evaluation, Preclinical , Drug Interactions , Drug Therapy, Combination/methods , Female , France , Humans , Hydroxychloroquine/pharmacokinetics , Mice , Neoplasms/immunology , Oxaliplatin/administration & dosage , Oxaliplatin/pharmacokinetics , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purificationABSTRACT
A 17-year-old man with osteosarcoma of the proximal humerus was planned for possible limb salvage surgery after standard neoadjuvant chemotherapy. However, during the surgical phase of treatment, the COVID-19 or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) outbreak occurred changing the healthcare landscape due to uncertainty regarding the virus, risk of COVID-19 infection and complications, and implementation of an enhanced community quarantine restricting movement of people within cities. Instead of limb salvage surgery, the patient underwent a forequarter amputation. Exposure to the virus in a high-risk hospital setting was minimised with patient discharge after a short hospital stay and home convalescence monitored by video conferencing. Multidisciplinary sarcoma team meetings with family members and a sarcoma navigator nurse were crucial in managing expectations and deciding on appropriate treatment in the setting of a novel infectious disease causing a pandemic.