23 septiembre 2020

ZepZelCaTM Nuevas Expectativas : Será Interesante Saber Si la Lurbinectedina Podría Ser Útil Como Tratamiento de Primera Línea, Evitando Así Que el Paciente Con Cáncer de Pulmón Microcítico Sufra una Quimioterapia Debilitante ( Y Quizás Incluso Inmunosupresora ) a Base de Platino . También Será Importante Aclarar Si Podría Combinarse Ventajosamente con Inhibidores de Puntos de Control Inmunitarios (ICI) Dirigidos a la Interacción PD-1 / PD-L1 .

 Small Cell Lung Cancer is a Disease With a Notoriously Bad Prognosis. 

The Initial Treatment is usually a combination of Platinum compounds (cisplatin or carboplatin) with etoposide that often leads to a partial or even apparently complete response, yet is invariably followed by a relapse of the disease that then manifests in a chemotherapy-resistant form.


 It should be noted that cisplatin and etoposide are rather poor ICD inducers, providing an explanation for this observation.

Although both drugs kill a substantial portion of tumor cells, they are unable to induce an immune response that would provide long-term effects to the patients. From this perspective, the introduction of a potent ICD inducer like lurbinectedin into the clinics (Figure 1a), initially as a second-line treatment appears a logical development.

Although the formal proof for this conjecture is still elusive, two interesting future developments await urgent exploration. 


*.- First, it will be interesting to know whether lurbinectedin might be useful as a first-line treatment, thus avoiding the patient with small-cell lung cancer to endure a debilitating (and perhaps even immunosuppressive) platinum-based chemotherapy .


*.- Second, it will be important to clarify whether lurbinectedin might be advantageously combined with immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 interaction (
Figure 1c). Indeed, for other cancers, there are multiple examples in which ICD inducers have been successfully combined with ICIs, both preclinically and clinically,9 strongly suggesting that this might be an adequate strategy for the clinical management of small-cell lung cancer.