Efficacy of antitumor therapy schemes with carboplatin in an experimental model of lung carcinoma and drug-resistant tuberculosis

Introduction. Up to 20% of tuberculosis patients suffer from malignant neoplasms. In this case, the combination of both diseases in the lung is a particular problem. More than 60% of patients cannot complete combination therapy due to drug-resistant MBT. The aim of the study was a preclinical study of the efficacy and safety of combination regimens of antitumor therapy using carboplatin and antituberculosis therapy for drug-resistant tuberculosis. The study was supported by grant No.22-15-00470 from the Russian Science Foundation (https://rscf.ru/project/22-15-00470/)

Material and methods. The study was conducted on 40 C57BL/6 mice aged two months with pre-modeled combined pathology of lung carcinoma and tuberculosis. Depending on the therapy, 4 groups were formed: I – control without treatment (n = 10), II – antitumor (carboplatin + paclitaxel) + antituberculosis therapy (n = 10), III – antitumor (carboplatin + pemetrexed) + antituberculosis therapy (n = 10), IV – antitumor (carboplatin + gemcitabine) + antituberculosis therapy (n = 10). The antituberculosis therapy regimen included moxifloxacin, linezolid, bedaquiline and perchlozone. The antitumor effect (tumor growth index, tumor growth inhibition), antituberculosis effect (CFU per lung weight), toxicity (biometric parameters of internal organs), and survival were assessed. Statistical processing was performed using non-parametric statistics methods.

Results. The lowest average body weight was recorded in the control group. The average body weight of the experimental animals correlated with the tumor node volume. The smallest tumor volume was recorded in the control, and the largest in group IV. The optimal anti-tuberculosis effect was achieved in all experimental groups. At the same time, significantly better survival, as well as signs of lower toxicity were noted in the group where anti-tuberculosis therapy was used in combination with carboplatin and gemcitabine.

Conclusion. A preclinical study of the efficacy and safety of combined anti-tuberculosis and antitumor therapy with carboplatin based on a combination model of Lewis pulmonary carcinoma and drug-resistant tuberculosis showed an optimal anti-tuberculosis effect in all groups. At the same time, acceptable toxicity and better survival indicate a greater safety of the combination of anti-tuberculosis therapy with carboplatin and gemcitabine.