Thalidomide for refractory hemorrhagic chronic radiation proctitis secondary to pelvic malignancy radiotherapy: A phase II clinical trial

BACKGROUND Radiotherapy, a cornerstone for the treatment of pelvic malignancies, often causes pelvic-abdominal organ damage, with chronic radiation proctitis (CRP) as the primary toxicity. Over 90% of CRP patients experience persistent, irreversible hematochezia, and its management is challenging due to the limited availability of effective drugs. AIM To evaluate the efficacy and safety of thalidomide in CRP patients suffering from intractable bleeding. METHODS A single-arm, open-label, phase II clinical trial was implemented to evaluate the therapeutic efficacy and safety of thalidomide in treating hemorrhagic CRP. Patients who had a diagnosis of hemorrhagic CRP with a Subjective Objective Management Analysis system (SOMA) score for hematochezia ≥ 2, or a transfusion history resulting from CRP, were given 50 mg thalidomide orally for 4 months. The primary endpoint was assessment of the therapeutic efficacy of thalidomide. RESULTS From October 2020 to February 2024, 62 individuals were enrolled, of whom the median SOMA score was 3 (interquartile range 3-4), and 8 (12.9%) patients were transfusion-dependent due to hematochezia resulting from CRP. The overall efficacy rate of thalidomide in improving the SOMA score was 83.9% (52 of 62), with rates of 58.3% (7 of 12, ≤ 2 months), 95.1% (39 of 41, 3-6 months), and 100% (6 of 6, > 6 months). Significant improvements in endoscopic manifestations were visually observed in 60% (21 of 35) of patients. Adverse events occurred in 37.1% (23 of 62) of the study patients, all categorized as the National Cancer Institute’s Common Terminology Criteria for Adverse Events grade 1-2 manifestations. CONCLUSION Thalidomide is effective and well-tolerated for the treatment of hemorrhagic CRP. Further prospective multicenter research is warranted to verify these findings.