Bleomycin is a drug used to treat certain cancers, such as Hodgkin lymphoma and germ cell tumours. But, bleomycin chemotherapy can cause near-fatal lung damage, a condition called bleomycin-induced lung injury. Now, in a recent study, researchers from Japan have explored the risk factors for this condition. Their findings bring to light safer chemotherapeutic regimens that can minimize side effects, paving the way for improvements in cancer therapy.
Previous studies in experimental animal models have shown that the “renin angiotensin-aldosterone” system (RAAS), a set of blood-pressure-regulating hormones, aggravates several lung disorders including BLI. Moreover, RAAS inhibitors (which can lower blood pressure) have been reported to reduce lung damage. Yet, the precise role of blood pressure and RAAS inhibitors in BLI has remained unclear until now.
Researchers from Japan, led by Dr. Ryujiro Hara from Tokai University School of Medicine, set out to bridge this gap, in a new study published in Clinical Lymphoma, Myeloma and Leukemia.
They retrospectively studied 190 patients treated with BLM for Hodgkin lymphoma or germ cell tumours. Discussing the long-term implications of their study, Dr. Hara says, “By finding an alternative to bleomycin for patients who are prone to developing BLI, complications can be suppressed, leading to improved clinical outcomes. We wanted to understand how hypertension impacts the onset of BLI and whether any potential combined drug interventions can help minimize the lung damage.”
The researchers found that 11.1% of the patients presented with symptomatic BLI upon BLM treatment. Interestingly, most patients who developed BLI received a lower dose of BLM than those who did not present with BLI. Thus, while withdrawing BLM treatment early after the onset of symptoms reduced damage, the dose of BLM did not correlate with the onset of BLI. The researchers also found that factors like age, hypertension, and estimated creatinine clearance (CCr; which is indicative of kidney function) were strongly correlated with the development of BLI; a significantly higher number of BLI cases were observed in patients above 63 years or with CCr < 100.7 mL/min and with a history of hypertension.
Next, to understand the effect of antihypertensive agents like RAAS inhibitors on BLI, the researchers analyzed patient cases with a history of hypertension. They found that only 12.5% of patients administered with RAAS inhibitors developed BLI, as compared to a substantial 53.3% of those who were not. Further, the risk of death was found to be highest in patients with a history of hypertension. These findings establish hypertension as an independent risk factor for BLI in patients who receive BLM treatment.
Highlighting the importance of their findings, Dr. Hara remarks, “The combined use of RAAS inhibitors and BLM prevents lung injury and has the potential to be the standard of care for patients with Hodgkin lymphoma and germ cell cancers, by minimizing the incidence of lung damage.”
Thus, BLM and antihypertensive drugs may, indeed, work in tandem to reduce the side effects of chemotherapy. This novel drug combination is a beacon of hope for millions of people suffering from cancer.
Paper: Authors: Ryujiro Hara, R., et al. The Role of Hypertension and Renin-angiotensinaldosterone System Inhibitors in Bleomycin-induced Lung Injury. Clinical Lymphoma, Myeloma and Leukemia. DOI: 10.1016/j.clml.2020.10.004
Image and Source: Tokai University