Prophylactic Nanocrystalline Megestrol Acetate Versus Placebo for Chemoradiotherapy-Related Anorexia in Nasopharyngeal Carcinoma

Inclusion Criteria:

* Newly diagnosed, histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma, clinical stage II-III according to the American Joint Committee on Cancer (AJCC) 9th edition staging system, and planned to receive concurrent chemoradiotherapy (CCRT).
* No prior radiotherapy to the primary tumor.
* Induction chemotherapy may be administered at the investigator's discretion according to local guidelines.
* Aged 18-70 years, male or female.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Able to comply with the study procedures and voluntarily provide written informed consent.
* Adequate organ function, defined as follows:

  * Hematologic function: neutrophil count ≥1.5 × 10⁹/L, hemoglobin ≥90 g/L, and platelet count ≥100 × 10⁹/L.
  * Coagulation function: international normalized ratio (INR), prothrombin time (PT), or activated partial thromboplastin time (aPTT) ≤1.5 × the upper limit of normal (ULN).
  * Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, total bilirubin ≤2.0 × ULN, and serum albumin ≥30 g/L.
  * Renal function: serum creatinine ≤1.5 × ULN or calculated creatinine clearance (CrCl) ≥60 mL/min using the Cockcroft-Gault formula.

Exclusion Criteria:

* Prior antitumor therapy, including chemotherapy, radiotherapy, or surgery, other than induction chemotherapy permitted according to the study protocol.
* Pregnant or breastfeeding women.
* Inability to comply with regular follow-up because of psychological, social, familial, or geographical factors.
* Concurrent participation in another clinical study involving investigational treatment during the study treatment period.
* Known allergy to any chemotherapeutic agent that may be used in the study.
* Severe uncontrolled infection or other serious uncontrolled medical illness.
* Major organ dysfunction, including decompensated cardiac, pulmonary, renal, or hepatic failure, that would preclude tolerance of chemoradiotherapy.
* Conditions that may substantially affect drug administration, distribution, metabolism, or excretion, including significant psychiatric disorders, central nervous system disorders, chronic diarrhea, ascites, or pleural effusion.
* Long-term use of immunosuppressive agents following organ transplantation.
* History of another malignancy before enrollment.
* Conditions affecting gastrointestinal absorption or oral intake, including dysphagia, malabsorption, or uncontrolled vomiting; difficulty with food intake or requirement for enteral or parenteral nutritional support; anorexia nervosa or anorexia related to psychiatric illness; or difficulty eating because of pain.
* Current or planned use of other medications that may increase appetite or body weight, including systemic corticosteroids (except short-term dexamethasone administered during chemotherapy), androgens, progestogens, thalidomide, olanzapine, anamorelin, or other appetite stimulants.
* Cushing syndrome, adrenal insufficiency, or pituitary insufficiency; poorly controlled diabetes mellitus; or uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg despite oral antihypertensive therapy.
* Thromboembolic disease, ascites, or lower-extremity edema within 6 months before the first dose of study treatment; history of esophageal or gastric varices, severe gastrointestinal ulceration, gastrointestinal perforation and/or fistula, gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), intra-abdominal abscess, or acute gastrointestinal bleeding.
* Known hypersensitivity to any component of the study drug.
* Any other condition that, in the investigator's judgment, would make the patient unsuitable for participation in the study.