Internal Radiation Therapy in Treating Patients With Liver Metastases From Neuroendocrine Tumors

Clinical Trial of Sir-Spheres® in Patients With Symptomatic or Progressive Hepatic Metastases From Neuroendocrine Tumors

RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PURPOSE: This phase II trial is studying how well internal radiation therapy works in treating patients with liver metastases from neuroendocrine tumors.

OBJECTIVES:

Primary

• Determine tumor response to selective internal radiation therapy with yttrium Y 90 resin microspheres (Sir-Spheres®) in patients with progressive liver metastases from neuroendocrine tumors.

Secondary

• Determine the toxicity of this treatment in these patients.
• Determine the symptomatic relief of patients treated with this regimen.
• Determine the health-related quality of life of patients receiving this treatment.

OUTLINE: Patients have an catheter placed into the hepatic artery percutaneously through the groin and then undergo selective internal radiation therapy with yttrium Y 90 resin microspheres (Sir-Spheres®) via the catheter on day 1. Patients also receive octreotide acetate IV 1 hour prior to, during, and 2 hours after Sir-Spheres® injection. Patients may undergo above treatment in another lobe of the liver (if each lobe is treated separately) 4 weeks later.

Patients undergo functional performance, health-related quality of life, and symptom severity assessment prior to initial treatment and after completion of study treatment.

After completion of study treatment, patients are followed periodically for at least 1 year.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Pathologically confirmed neuroendocrine tumor metastatic to the liver

  • Well-differentiated or moderately well-differentiated neuroendocrine tumors

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral CT scan

• Symptomatic disease, meeting one of the following criteria:

  • Refractory carcinoid symptoms, defined as Carcinoid Symptom Severity scale > 2 despite use of octreotide acetate at ≥ 200 mcg subcutaneously three times daily (or 20 mg intramuscularly once monthly) for ≥ 4 weeks

  • Evidence of radiographic progression with either of the following manifestations:

    • Moderate-severe right upper quadrant pain and unintentional weight loss > 10%
    • Decline in Karnofsky performance status > 10 points

• At least a 20% increase in the sum of the longest diameters of target lesions in the liver within the past 12 months

• No more than 75% replacement of normal liver by neuroendocrine tumor

• No more than 20% arteriovenous lung shunting on a technetium Tc 99m macro-aggregated albumin nuclear scan

• No equivocal, nonmeasurable, or nonevaluable liver metastasis

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%
• Life expectancy ≥ 6 months
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Creatinine ≤ 1.5 mg/dL
• Bilirubin ≤ 2.0 mg/dL
• Albumin ≥ 3.0 g/dL
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 65,000/mm³
• Hemoglobin > 9.0 g/dL
• INR ≤ 1.4
• No hepatic arterial anatomy that would preclude the administration of study treatment into the liver
• No nonmalignant disease that would preclude study participation
• No other malignancy within the past 5 years except for cured basal cell carcinoma of the skin or cured carcinoma in situ of the uterine cervix

PRIOR CONCURRENT THERAPY:

• Prior surgery, chemotherapy, or locally ablative technique for the liver cancer allowed
• No prior radiotherapy to the upper abdomen that includes the liver in the treatment field
• No investigational drug or agent/procedure (i.e., participation in another clinical trial) within the past 4 weeks
• No other specific anticancer treatment (other than octreotide acetate) during and for 3 months after completion of study therapy