Oral pirfenidone in patients with chronic fibrosis resulting from radiotherapy: a pilot study

Nicole L Simone, Benjamin P Soule, Lynn Gerber, Elizabeth Augustine, Sharon Smith, Rosemary M Altemus, James B Mitchell, Kevin A Camphausen, Nicole L Simone, Benjamin P Soule, Lynn Gerber, Elizabeth Augustine, Sharon Smith, Rosemary M Altemus, James B Mitchell, Kevin A Camphausen

Abstract

Background: Fibrosis is a common side effect after treatment with ionizing radiation. Several methods to ameliorate debilitating fibrosis have been employed but without consistent results. The goal of this pilot study is to determine if Pirfenidone, a novel regulator of cytokine gene expression, has the potential to ameliorate established radiation-induced fibrosis.

Methods: Open label, prospective pilot study of 800 mg three times/day, orally administered Pirfenidone was administered to enrolled patients who were had completed radiation therapy and who had established radiation-induced fibrosis. Range of motion (ROM) was assessed using standard measures, and subjective measures of pain, fatigue, disability and global health were measured every three months.

Results: Seven patients were enrolled of whom 3 had ROM assessments of 1 site and 2 had ROM assessments of 2 sites. Of these assessments, 6 revealed increased ROM during drug intervention while 1 revealed a decreased ROM. There was an overall improvement in the mental composite score of the SF36 while physical composite score was decreased and the vitality score was unchanged. Two patients were removed from the study because of syncopal episodes.

Conclusion: Several patients experienced improved function of at least 25% and reported subjective improvement. Pirfenidone may benefit patients with radiation-induced fibrosis and is worthy of a larger well controlled trial.

Figures

Figure 1
Figure 1
Average SF36 Component Scores. The average score for all patients for each component of the SF36 is shown. During drug therapy, the vitality component score shows little change (-3%), the physical composite score decreases by 33% while the mental composite score shows an increase of 17%.
Figure 2
Figure 2
Total Range of Motion Measurements. The total ROM (sum for all planes of motion) was calculated for each patient for the cervical spine, upper extremity and lower extremity. Maximum possible total ROM is represented at the top of each graph by a dotted line. Each patient is represented individually. For the four patients with cervical ROM measurements, Patient 1 showed an improvement of 73%, Patient 2 improved by 31%, and Patient 3 improved by 24%. Patient 4 had a decline in function of 8%. Both patients with upper extremity ROM measurements show an improvement of over 100 degrees of ROM during the drug therapy with Patient 1 showing a 15% improvement and Patient 2 improving by 10%. For the single patient with lower extremity ROM measurements, there is a total improvement of approximately 50 degrees of ROM during the drug therapy which is 11% above baseline.

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