Application of KANG FU PEN in Radical Concurrent Radiotherapy and Chemotherapy for Cervical Cancer to Prevent and Treat Radiation-induced Rectal Injury

Application of KANG FU PEN (Protective Irrigation Solution Against Rays) in Radical Concurrent Radiotherapy and Chemotherapy for Cervical Cancer to Prevent and Treat Radiation-induced Rectal Injury：a Multicenter, Prospective, Randomized Trail

A total of 520 cases will be randomly divided into Kang Fu Pen (liquid dressing) enema intervention group (experimental group) and non-enema intervention group (control group), according to the ratio of 1:1.

All patients are planned to receive radical concurrent chemoradiotherapy. Intensity modulated radiotherapy (IMRT) will be used for external irradiation, with a dose of 45-50.4Gy /25-28 fractions. Combined three-dimensional intracavitary/interstitial (IC/IS) brachytherapy was applied. The preferred dose fraction plan is 6Gy*5 fractions, or 7Gy*4 fractions. Whether to adopt supplement radiotherapy can be decided by the tumor regression. Cisplatin 40 mg/m2 is recommended as the first choice for concurrent chemotherapy, and TP or TC can also be considered. Single-drug weekly therapy should be completed for at least 3 cycles, and combined 3-week regimen should be completed for at least 1 cycle.

Experimental group: from three days before radiotherapy to one week after radiotherapy, Kang Fu Pen (recombinant human superoxide dismutase) retention enema, 50ml/ time, once every other day. When rectal mucosa II degree reactions (NCI-CTCAE 5.0) occur, it is changed to 1 day/time until 1 week after mucosal remission.

Control group: 3 days before radiotherapy to the end of radiotherapy, no drug retention enema was used.

Inclusion Criteria:

1. The patient is completely voluntary and has the ability to sign the research informed consent form within 30 days before enrollment;
2. Age ≥18 years old and ≤65 years old;
3. Pathologically confirmed cervical cancer;
4. Those with IB3, IIA2, IIB, IIIA, IIIB, and those with cervical tumor ≥ 4cm or involved parametrial in IIIC1 and IIIC2 (FIGO 2018 staging);
5. ECOG score 0-2 points;
6. The complete blood count and basal metabolic indexes in the 14 days before enrollment must meet the following requirements: NEUT≥1.5*10^9/L, HGB≥80g/L, PLT≥100*10^9/L, blood creatinine < 1.5mg/dl (133umol/L), AST and ALT are within 2 times of the upper limit of normal;
7. Those who have had regular bowel movements and had a negative stool routine test + occult blood before enrollment.

Exclusion Criteria:

1. Those who have a history of allergy to superoxide dismutase use;
2. Patients with skin and mucous membrane infections, patients with obvious empyema or pelvic inflammatory disease;
3. Those who have had chronic colitis, ulcerative colitis, and non-specific proctitis in the past;
4. Those who have received cervical cancer surgery (including pelvic or retroperitoneal lymphadenectomy, excluding tumor biopsy), radiotherapy or chemotherapy;
5. Those who are expected to be unable to receive brachytherapy, or brachytherapy needs to use tumor elimination, uterine tube inserted alone in one fraction, or template plan;
6. Those who need to use fluorouracil or capecitabine or tigio in the concurrent chemotherapy regimen;
7. History of other malignant tumors;
8. Pregnant or lactating women;
9. Accompanied by active infection and fever;
10. Other serious diseases that may significantly affect the compliance of clinical trials, such as unstable heart disease, kidney disease, chronic hepatitis, poorly controlled diabetes, and mental illness that require treatment.