Does Esbriet (Pirfenidone) Cause Adenocarcinoma?
No, there is no evidence in humans that Esbriet (pirfenidone) causes adenocarcinoma, but animal studies show increased hepatocellular adenoma and carcinoma in rodents at high doses, and uterine adenocarcinoma in female rats at doses 3 times the maximum recommended human dose. 1
Evidence from Animal Studies
The FDA drug label provides the most definitive information on this topic:
In a 24-month carcinogenicity study in Fischer rats, pirfenidone caused statistically significant dose-related increases of hepatocellular adenoma and carcinoma in male rats at doses of 750 mg/kg and above (approximately 1.9 times adult exposure at the maximum recommended human dose). 1
In female rats, there were statistically significant increases of the combination of hepatocellular adenoma and carcinoma and the combination of uterine adenocarcinoma and adenoma at a dose of 1,500 mg/kg/day (approximately 3.0 times adult exposure at the maximum recommended human dose). 1
In mice, pirfenidone caused statistically significant dose-related increases of hepatocellular adenoma, carcinoma, and hepatoblastoma at high doses. 1
Human Safety Data
Despite the findings in animal studies, the clinical relevance of these tumor findings in rodents to humans remains unknown. The available human data does not demonstrate a clear link between pirfenidone and adenocarcinoma:
A 2013 review noted 3 cases of bladder cancer in pirfenidone groups versus 1 case in placebo groups in clinical trials, but this was not sufficient to establish causation. 2
A 2018 study actually suggested that pirfenidone might correlate with a decreased risk of lung cancer in patients with idiopathic pulmonary fibrosis (IPF), with significantly lower incidence of lung cancer in the pirfenidone group compared to the non-pirfenidone group (2.4% vs. 22.0%). 3
Mechanism of Action and Anti-Cancer Potential
Interestingly, some research suggests pirfenidone may have anti-cancer properties:
Pirfenidone has been shown to inhibit cell proliferation and arrest the cell cycle in hepatic stellate cells. 4
A 2017 study demonstrated that pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma, a process associated with cancer invasion and metastasis. 5
Clinical Implications
When considering pirfenidone therapy:
The primary indication for pirfenidone is idiopathic pulmonary fibrosis in patients with mild-to-moderate disease (FVC ≥50% predicted and DLCO ≥35% predicted). 6
Regular monitoring is essential, including baseline liver function tests before starting pirfenidone, with monthly liver function tests for the first 6 months and every 3 months thereafter. 6
The benefit-risk profile of pirfenidone should be carefully considered, especially in patients with risk factors for cancer.
Conclusion
While animal studies show an increased risk of certain tumors including adenocarcinoma at high doses, there is currently insufficient evidence to conclude that pirfenidone causes adenocarcinoma in humans. Some research even suggests potential anti-cancer effects. As with any medication, the benefits of treatment must be weighed against potential risks, and patients should be monitored appropriately.