Pilot trial of bone-targeted therapy with zoledronate, thalidomide, and interferon-gamma for metastatic renal cell carcinoma.
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.
Tannir
Nizar
N
Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77230, USA.
Jonasch
Eric
E
Pagliaro
Lance C
LC
Mathew
Paul
P
Siefker-Radtke
Arlene
A
Rhines
Laurence
L
Lin
Patrick
P
Tibbs
Rita
R
Do
Kim-Anh
KA
Lin
Sue-Hwa
SH
Tu
Shi-Ming
SM
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000556:secondary*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D013792:Thalidomide / Q000627:therapeutic use*; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D013792:Thalidomide; D000077211:Zoledronic Acid; D007371:Interferon-gamma