Scientists reveal that high blood pressure increases lung damage risk in patients with cancer who receive bleomycin chemotherapy.
Bleomycin is a drug used to treat certain cancers, such as Hodgkin lymphoma and germ cell tumors. 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.
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Chemotherapy is the go-to treatment option for cancer but is often accompanied by adverse side effects. One widely used anti-cancer drug in chemotherapy is bleomycin (BLM): it is the primary treatment against certain cancers like Hodgkin lymphoma, cancer of the lymphatic system, and testicular and ovarian cancer. However, about one-third of the patients treated with bleomycin develop a near-fatal lung complication, called “bleomycin-induced lung injury” (BLI). Thus, identifying risk factors that can lead to BLI in patients is crucial.
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 tumors. 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.
Image credit: Tokai University
Reference
Authors: Ryujiro Hara (1), Makoto Onizuka (1), Sawako Shiraiwa (1), Kaito Harada1, Yasuyuki Aoyama1, Daisuke Ogiya1, Masako Toyosaki1, Rikio Suzuki (1), Sinichiro Machida (1), Ken Ohmachi (1), Yoshiaki Ogawa (1), Hiroshi Kawada (1), Shigeki Watanabe (2), Akira Miyajima (3), Ryota Masuda (4), Masayuki Iwazaki (4), Mikio Mikami (5), Takashi Koike (6), Hiroyuki Mochizuki (6), Kiyoshi Ando (1)
Title of original paper: The Role of Hypertension and Renin-angiotensinaldosterone System Inhibitors in Bleomycin-induced Lung Injury
Journal: Clinical Lymphoma, Myeloma and Leukemia
DOI: 10.1016/j.clml.2020.10.004
Affiliations:
(1) Division of Hematology/Oncology, Department of Internal Medicine, Tokai University
(2) School of Medicine, Isehara, Kanagawa, Japan
(3) Department of Hematology, Ebina General Hospital, Kanagawa, Japan
(4) Department of Urology
(5) Department of General Thoracic Surgery
(6) Department of Obstetrics and Gynecology
(7) Department of Pediatrics, Tokai University School of Medicine, Isehara, Kanagawa, Japan
About Dr. Ryujiro Hara from Tokai University
Dr. Ryujiro Hara, the lead author of this study, is currently a faculty member at the Department of Hematology and Oncology, Department of Internal Medicine, Tokai University School of Medicine, Japan. His work is focused on risk assessment and development of novel therapies for cancer, particularly for lymphoma and leukemia. He has authored several peer-reviewed publications in these research domains.