Safety and Efficacy of RIF Combined With Anlotinib in the Treatment of Patients With Advanced Recurrent Platinum-Resistant Ovarian Cancer: A Prospective, Multicenter Clinical Study

Inclusion criteria

• The patient voluntarily participates in this study and signs the informed consent form.
• Female aged 18-70 years.
• Histologically confirmed advanced (FIGO stage III/IV) serous or ovarian endometrioid carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma.
• Disease recurrence within 6 months after the last platinum-based chemotherapy or progression during chemotherapy (i.e., platinum-resistant or platinum-refractory).
• ECOG performance status of 0 or 1, with an expected survival of ≥4 months.
• Adequate organ function, meeting the following laboratory criteria within 14 days before enrollment:

• **Complete blood count (without transfusion within 14 days):**

• Hemoglobin (Hb) ≥80 g/L;
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
• Platelet count (PLT) ≥80×10⁹/L.
• **Biochemical tests:**

• Total bilirubin ≤1.5×ULN (upper limit of normal);
• ALT and AST ≤2.5×ULN (≤5×ULN if liver metastases are present);
• Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
• **Cardiac function:** Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%).
• Ability to take oral medications.
• ≥4 weeks since the last chemotherapy, radiotherapy, targeted therapy, immunotherapy, or other antitumor treatments before the first dose of study drugs.
• Women of childbearing potential must agree to use highly effective contraception during the study and for 6 months after the last dose. A negative serum or urine pregnancy test within 7 days before enrollment is required, and the patient must be non-lactating.

Exclusion criteria

• Prior treatment with arsenic agents (e.g., arsenic trioxide, Compound Huangdai Tablets) or anlotinib hydrochloride/other targeted therapies.

• Known hypersensitivity to anlotinib or its excipients. 3. Known hypersensitivity to arsenic agents or their excipients. 4. **Comorbidities/medical history:**

• Clinically significant hemoptysis (>50 mL/day within 3 months before enrollment) or active bleeding (e.g., gastrointestinal hemorrhage, hemorrhagic gastric ulcer, baseline fecal occult blood ≥++), or vasculitis.
• Arterial/venous thromboembolic events within 6 months (e.g., cerebrovascular accident, deep vein thrombosis [unless catheter-related and resolved], pulmonary embolism).
• Uncontrolled hypertension (systolic >140 mmHg or diastolic >90 mmHg despite medication) or history within 6 months of myocardial infarction, severe/unstable angina, NYHA class ≥2 heart failure, clinically significant arrhythmias, or symptomatic congestive heart failure.
• Interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., pulmonary fibrosis, acute pneumonia).
• Renal insufficiency: urine protein ≥++ or 24-hour urine protein ≥1.0 g.
• Live attenuated vaccination within 28 days before the first dose or planned during the study.
• HIV infection or AIDS; active hepatitis (HBV-DNA ≥500 IU/mL; HCV-RNA above detection limit) or coinfection with HBV/HCV.
• Severe infection within 4 weeks (e.g., bacteremia, severe pneumonia requiring hospitalization) or active infection (CTCAE ≥grade 2) requiring systemic antibiotics within 2 weeks; unexplained fever >38.5°C during screening (unless tumor-related per investigator); active tuberculosis within 1 year.
• Other malignancies within 3 years (except adequately treated basal cell carcinoma, squamous cell skin cancer, or cervical carcinoma in situ).
• Palliative radiotherapy to >20% bone marrow within 1 week; history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Major surgery within 28 days (diagnostic biopsies or PICC placement allowed).
• Prior or planned allogeneic bone marrow or solid organ transplantation.
• Peripheral neuropathy ≥grade 2; active brain metastases, leptomeningeal disease, or spinal cord compression (stable brain metastases treated ≥14 days before enrollment allowed if no hemorrhage on MRI/CT).

• Current/recent (within 30 days) use of another investigational drug or participation in another clinical trial.

• Conditions severely affecting oral drug absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction).

• Any condition that may interfere with study results or compliance, per investigator judgment.