Thalidomide in the Treatment of Chronic Radiation Proctitis With Intractable Bleeding

Prospective, Open Clinical Trial of Thalidomide in the Treatment of Chronic Radiation Proctitis With Intractable Bleeding

Chronic radiation proctitis (CRP) is the main secondary toxic injury after pelvic radiotherapy. Hematochezia is the most common symptom for more than 80% of CRP patients.

Non-surgical treatment is the first choice to the treatment of CRP to avoid the occurrence of serious complications. Conventional oral medication for the treatment of bleeding CRP is very few and has little effect. At present, no oral medication has been found to significantly alleviate and control refractory bleeding of CRP. Therefore, it is an urgent problem to screen out a drug that is more effective, safe and highly compliant for the treatment of hemorrhagic CRP.

Thalidomide has anti-inflammatory, immune regulation, anti-angiogenesis and other effects. For the patients of CRP with intractable bleeding, a prospective, open clinical trial will be carried out to observe the safety and effectiveness of thalidomide in treating hemorrhagic CRP.

Radiotherapy is an essential therapeutic tool for pelvic malignancies such as uterine cervix, uterine corpus, prostate, testicular, urinary bladder and rectal cancers. According to reports, the estimated number of new cases of malignant pelvic tumors in China in 2015 alone exceeded 500,000. Chronic radiation proctitis (CRP) is an unavoidable and commonly observed side effect, occurs 3 months later and in 5-20% of patients after pelvic malignancy radiation. Hematochezia is the most common symptom for more than 80% of CRP patients, which is a persistent, irreversible and progressive symptom, and will probably give rise to anemia. In clinic, the treatment for intractable bleeding of CRP is very difficult.

Non-surgical treatment is the first choice to the treatment of CRP to avoid the occurrence of serious complications. Conventional oral medication for the treatment of bleeding CRP is very few and has little effect. At present, no oral medication has been found to significantly alleviate and control refractory bleeding of CRP. Therefore, it is an urgent problem to screen out a drug that is more effective, safe and highly compliant for the treatment of hemorrhagic CRP.

Thalidomide has anti-inflammatory, immune regulation, anti-angiogenesis and other effects. A large number of studies have shown that thalidomide can be used to treat Crohn's disease, ulcerative colitis, radiation cystitis, etc., and it can treat moderate to severe of IBD patients can inhibit inflammatory response, improve clinical symptoms, promote intestinal mucosal repair. Further, recent studies have proved that thalidomide can be used to treat intestinal bleeding due to vascular dysplasia. And a case report from Gut described that refractory bleeding of CRP of a 78-year-old woman were significantly alleviated after taking thalidomide.

Therefore, for the patients of CRP with intractable bleeding, a prospective, open clinical trial planed to carry out to observe the safety and effectiveness of thalidomide in treating hemorrhagic CRP.

Inclusion criteria

1. Patients aged 18-75 years;
2. Patients with ECOG physical condition score of 0-2;
3. Patients with previous pathological diagnosis of pelvic tumors (Gynecology, prostate, urinary system);
4. Patients with a history of pelvic radiotherapy, at least 6 months from the end of the last radiotherapy;
5. Patients with no primary tumor recurrence or metastasis;
6. Patients with refractory hemorrhagic CRP who have failed to conventional treatment (SOMA score for hematochezia≥2, hemoglobin level ≤90g/L, or a history of blood transfusion due to CRP)
7. Subjects and their family members can understand the research plan, and are willing to participate, and sign an informed consent form.

Exclusion Criteria:

1. Patients with active bleeding requiring emergency treatment;
2. Patients with severe complications of CRP, such as Rectal ulcer (VRS>Grade 3) or fistula, perforation, stenosis, necrosis, perianal intractable pain and so on
3. Patients with a history of rectal resection;
4. Other bleeding diseases, such as grade III or IV hemorrhoids, coagulation dysfunction, etc.;
5. Patients with other diseases requiring long-term use of anticoagulant drugs;
6. Combined intestinal obstruction, requiring surgery;
7. The absolute value of neutrophils of patients is lower than 750/mm3;
8. Patients who are allergic to thalidomide;
9. Pregnant or lactating women;
10. Patients with severe mental illness;
11. Patients who cannot take medication or follow up as planned;
12. During the trial and within 3 months after the trial, the subjects and their partners are not willing to contraception;
13. Participants in other clinical investigators 3 months before the trial