Genistein in Treating Patients Undergoing External-Beam Radiation Therapy for Bone Metastases

• Safety [ Designated as safety issue: Yes ]
• Frequency of severe (grade 3) toxicities [ Designated as safety issue: Yes ]

• Time to pain relief, duration of pain relief, and degree of pain relief [ Designated as safety issue: No ]
• Incidence of pathologic fractures [ Designated as safety issue: No ]
• Effect of treatment on quality of life measures as assessed by the BPI and FACT-G [ Designated as safety issue: No ]

RATIONALE: Genistein may increase the effectiveness of radiation therapy in treating pain caused by bone metastases.

PURPOSE: This phase I/II trial is studying the side effects of genistein and to see how well it works in treating patients undergoing external-beam radiation therapy for pain caused by bone metastases.

OBJECTIVES:

• To determine whether genistein is safe when administered in combination with palliative external beam radiotherapy in patients with osseous metastases.
• To determine the time to pain relief, duration of pain relief, and degree of pain relief in patients treated with this regimen.
• To determine the incidence of pathologic fractures in patients treated with this regimen.
• To determine the effect of this regimen on quality of life measures in these patients.

OUTLINE: This is a multicenter study.

Patients undergo external beam radiotherapy once daily on days 1-10. Patients also receive oral genistein once daily on days 1-60.

Patients complete pain and quality-of-life questionnaires periodically.

After completion of study therapy, patients are followed at 30 days.

• Breast Cancer
• Kidney Cancer
• Lung Cancer
• Melanoma
• Metastatic Cancer
• Pain
• Prostate Cancer

• Dietary Supplement: genistein
  Genistein will be taken orally once daily as 500 mg capsules throughout the study (60 days).
  Other Name: Bonistein
• Radiation: radiation therapy
  A course of palliative external beam radiation therapy -performed within 8 weeks prior to start of the study.

Inclusion Criteria:

• Histologically confirmed malignant solid tumor, including any of the following:

  • Breast cancer
  • Lung cancer
  • Kidney cancer
  • Melanoma
  • Prostate cancer
• Radiographic evidence* of bone metastasis within the past 8 weeks NOTE: *Acceptable studies include plain radiograph, radionuclide bone scan, CT scan, and MRI

• Has pain that appears to be related to the radiographically documented metastasis, in the opinion of the treating physician, AND a decision has been made by the responsible clinician that a course of palliative external beam radiotherapy is appropriate treatment

  • "Worst pain score" of > 5 on a scale of 10 as scored on the pain assessment questionnaire (BPI) (question #3: 0 = no pain; 10 = worst possible pain) OR taking narcotic medications with an oral morphine equivalent dose of > 60 mg/day
  • No painful metastases to the skull, hands, or feet

• Eligible treatment sites include any of following:

  • Weight-bearing sites:

    • Pelvis (excluding pubis)
    • Femur
    • Sacrum and/or sacroiliac joints
    • Tibia

  • Non-weight-bearing sites:

    • Up to 5 consecutive cervical, thoracic, or lumbar vertebral bodies
    • Lumbosacral spine
    • Up to 3 consecutive ribs
    • Humerus
    • Fibula
    • Radius ± ulna
    • Clavicle
    • Sternum
    • Scapula
    • Pubis

• If multiple osseous sites are treated, the treatment site is included as weight-bearing if any of the sites include the pelvis, sacrum, femur, or tibia

  • Treatment of multiple osseous sites allowed only if those sites can be included in ≤ 3 treatment sites
• Patients with painful metastases that are contiguous but do not fit into the definition of a site listed above are eligible but are considered to have 2 treatment sites
• No vertebral metastases with clinical or radiographic evidence of spinal cord or cauda equina compression/effacement
• No primary hematologic malignancies (e.g., lymphoma)

• Hormone receptor status (for patients with breast cancer):

  • Estrogen receptor-negative tumor
• Menopausal status not specified
• Karnofsky performance status 40-100%
• Life expectancy ≥ 3 months
• ALT normal
• Bilirubin normal
• Serum creatinine normal (≤ 1.8 mg/dL for males and ≤ 1.5 mg/dL for females)
• Free T4 and thyroid-stimulating hormone normal
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No pathologic fracture or impending fracture of the treatment site
• No history of primary hyperparathyroidism
• No malabsorptive disease or chronic diarrhea
• No history of sarcoidosis or tuberculosis

Exclusion Criteria:

• Less than 30 days since prior systemic radioisotopes for pain, including Strontium-90 (^90Sr) or Samarium (^153Sm)
• Less than 30 days since prior antibiotics
• Less than 30 days since prior initiation of systemic therapy (e.g., hormonal therapy, chemotherapy, or immunotherapy)

• Less than 90 days since prior intravenous bisphosphonate therapy

  • Concurrent oral bisphosphonates allowed
• Prior radiotherapy or palliative surgery to the painful sites
• Concurrent surgical fixation of the bone
• Concurrent treatment to the skull, hands, or feet