The Impact of Everolimus and Radiation Therapy on Pulmonary Fibrosis

Abstract

Background and objectives: Everolimus (EVE) is a mammalian target of the rapamycin (mTOR) inhibitor that is widely used in cancer patients. Pulmonary toxicity, usually manifesting as interstitial pneumonitis, is a serious adverse effect of this drug. Radiation therapy, which is often administered in conjunction with chemotherapy for synergistic effects, also causes pulmonary fibrosis. In view of pulmonary damage development in these two forms of cancer treatment, we have examined the effect of EVE administration individually, in combination with radiation given in varying sequences, and its relation to the extent of pulmonary damage. Materials and Methods: We performed an experimental study in albino rats, which were randomized into five groups: (1) control group, (2) EVE alone, (3) EVE 22 h after radiation, (4) EVE 2 h after irradiation, and (5) only radiation. Sixteen weeks after thoracic irradiation, rat lung tissue samples were examined under light microscopy, and the extent of pulmonary damage was estimated. After this, we calculated median fibrosis scores in each group. Results: The highest fibrosis score was noted in Group 4. Among the five groups, the control group had a significantly lower median fibrosis score compared to the others. When the median fibrosis score of the group that received concurrent EVE with radiation therapy (RT) (Group 4) was compared with that of the control group, the difference was statistically significant (p = 0.0022). However, no significant differences were achieved among the study groups that received EVE only or RT only, whether concurrently or sequentially (p > 0.05). Conclusion: EVE is an effective treatment option for the management of several malignancies and is often combined with other therapies, such as radiation, for a more efficient response. However, an increased risk of pulmonary fibrosis should also be anticipated when these two modalities are combined, as they both can cause pulmonary damage, especially when administered concurrently.

Everolimus Alleviates Renal Allograft Interstitial Fibrosis by Inhibiting Epithelial-to-Mesenchymal Transition Not Only via Inducing Autophagy but Also via Stabilizing IκB-α

“…Recently, due to its immunosuppressive effect, EVR has garnered much greater attention as a molecular targeting drug ( 18 ). Meanwhile, EVR has anti-pulmonary fibrosis, anti-renal fibrosis, anti-arthrofibrosis, and anti-hepatic fibrosis therapeutic potential in addition to its widespread use in traditional anti-cancer therapies ( 21 , 29 , 30 ). However, overall safety data for EVR in CAD patients, obtained from controlled research with the CsA group, revealed that EVR was superior to measured glomerular filtration rate (mGFR), but was associated with more adverse events ( 19 ).…”

“…According to the latest research, it has been reported that EVR attenuates tacrolimus-induced renal interstitial fibrosis in rats through suppressed TGF-β1 production ( 20 ). However, one research demonstrated that EVR led to serious pulmonary fibrosis and interstitial pneumonitis after administration in some cancer patients ( 21 ). Similarly, EVR also has the double face during the progression of EMT and fibrosis in in hepatic stellate cell and human liver cancer cells ( 22 ).…”

Avaliação da função pulmonar de pacientes oncológicos submetidos a quimioterapia

“…Apesar de a cirurgia oncológica ser o procedimento que gera mais danos na função pulmonar quando comparada aos outros 33 , sabe-se que a radioterapia também tem efeitos deletérios sobre a funcionalidade respiratória, estando relacionada principalmente à dosagem e local de incidência 26 . Essas repercussões se dão pelo desenvolvimento de pneumonite actínica e fibrose pulmonar, que se manifestam de modo agudo e tardio, respectivamente 10 . Dessa forma, ressalta-se que fatores como a heterogeneidade dos pacientes no que diz respeito à realização de outro procedimento terapêutico prévio, como a própria radioterapia ou quimioterapia anterior, podem ter influenciado nos resultados obtidos na avaliação pulmonar desta amostra.…”

“…Apesar dos avanços no tratamento e sobrevida de pacientes com neoplasias 6 , a quimioterapia, apresenta complicações conhecidas e efeito adversos comuns como reações alérgicas, dor, fadiga e nauséas 7,8 . Porém, alguns medicamentos promovem um estresse oxidativo que contribuem para respostas inflamatórias e consequente fibrose pulmonar e toxicidade do organismo 9 , além de afetar diretamente na nutrição dos indivíduos, diminuindo assim a sua qualidade de vida e o seu bem-estar durante o tratamento 10,11 .…”