Supplementation of L-arginine in Patients With Non-resectable Brain Metastases

Oral L-arginine Supplementation in Patients With Non-resectable Brain Metastases Treated With Radiation Therapy With Palliative Intent

This study evaluates the nutritional supplement arginine as supportive measure for patients with unresectable metastatic brain tumors that receive radiation therapy with palliative intent

Brain metastasis, the most common intracranial tumor, is associated with neurological disability and short survival time. For selected patients this outcome can be improved by achieving greater local control. Virtually all cancer patients with brain metastases receive radiotherapy; a majority as part of their primary treatment while others in connection with surgery or palliation. Agents that increase the sensitivity of cancer cells to radiation may improve the control of the disease. Previous data indicates that arginine supplementation can modify the metabolism of cancer and immune cells making tumors more susceptible to standard treatments liked radiation. In this phase 1/2 comparative study the investigators will investigate whether 10 mg of arginine oral supplementation (compared to placebo administration) administered twice a day prior to the radiation therapy can modify tumor metabolism, immune response and effect of radiation. The primary end-points are safety and toxicity of arginine, quality-of-life and clinical response. The secondary end-points are imaging response and neurological progression-free survival. Additional exploratory end-points include intensity of radiation administered, effects on tumor metabolism by magnetic resonance spectroscopy, immune response by cytokine pattern in serum, body composition and nutritional parameters , overall survival and progression free survival

Patients with pathology-confirmed diagnostic of solid cancer and measurable brain metastases by CT scan and/or MRI

Inclusion Criteria:

• Unresectable criteria by neurosurgeon
• Recursive partitioning analysis (RPA) -Radiation Therapy Oncology Group (RTOG) class II (Karnofsky's performance score ≥ 70 and extracranial metastases and/or non-controlled primary tumor)
• Measurable brain lesion/s by contrast-enhanced CT or MRI
• Absolute granulocyte count more or equal than 2000/mm3
• Hemoglobin more or equal than 9 g/L (patients with lower levels were transfused before the randomization)
• Normal renal laboratory (serum creatinine <1.5 mg/dL and 24-h creatinine clearance >60 mL/min)
• Normal hepatic function (aspartate aminotransferase and alanine aminotransferase <2.5 times the upper limit of normal)
• Stable body weight and composition for at least one month prior enrollment

Exclusion Criteria:

• Prior treatment for brain metastases and/or brain tumor.
• Primary brain tumor
• Hematologic malignancies
• Solid tumors of germinal origin
• Contraindication for external radiation therapy.
• Allergy to L-arginine.