Pilot trial of bone-targeted therapy with zoledronate, thalidomide, and interferon-gamma for metastatic renal cell carcinoma

Cancer. 2006 Aug 1;107(3):497-505. doi: 10.1002/cncr.22038.

Abstract

Background: The purpose of the study was to evaluate the efficacy and safety of a bone-targeted regimen consisting of zoledronate, thalidomide, and interferon-gamma in patients with renal cell carcinoma and bone metastases.

Methods: Eligible patients had radiographic evidence of bone metastasis. Impending pathologic fractures or spinal cord compressions must have been controlled by surgery or radiation therapy before enrollment. Zoledronate (4 mg) was given intravenously every 4 weeks, thalidomide (300 mg) was given orally once a day, and interferon-gamma (100 microg) was given subcutaneously once a week. Patients were evaluated for time to skeletal-related events, the appearance of calcification in osteolytic metastases, and levels of the bone formation/resorption markers. RESULTS.: Fifteen patients were treated between November 2002 and November 2003; 12 had previously undergone surgery, radiation, or embolization for their bone metastases; 11 had more than 3 sites of bone involvement; and 9 also had nonosseous metastases in the lung, liver, lymph node, pancreas, or adrenal gland. The median time to progression was 8.3 weeks (range, 2.1-48 weeks). The median time to a skeletal-related event was 12.0 weeks (range, 3.9-46.4 weeks). Two patients discontinued treatment because of adverse drug reactions (1 deep venous thrombosis and 1 myocardial infarction). Two patients experienced pain improvement and developed calcification in osseous metastases; these patients also showed favorable changes in bone marker levels.

Conclusions: In this pilot study a bone-targeted regimen combining zoledronate, thalidomide, and interferon-gamma was well tolerated and might provide clinical benefit for a small subset of patients with renal cell carcinoma and bone metastases.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / urine
  • Bone Density Conservation Agents / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary*
  • Carcinoma, Renal Cell / secondary*
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Interferon-gamma / therapeutic use*
  • Kidney Neoplasms / secondary*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pilot Projects
  • Thalidomide / therapeutic use*
  • Zoledronic Acid

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Thalidomide
  • Zoledronic Acid
  • Interferon-gamma