A phase II trial of oral temozolomide in patients with metastatic renal cell cancer.
OBJECTIVE
To determine the activity of temozolomide, an oral imidazotetrazine alkylating agent that has exhibited broad antitumor activity in preclinical studies, in renal cell cancer (RCC) patients. METHODS. Metastatic RCC patients were treated with temozolomide, 200 mg/m(2) per day orally, and traditional radiologic response endpoints were assessed. O(6)-Alkylguanine-DNA alkyltransferase (AGT) activity was measured in four pretreatment biopsies.


RESULTS
Among 12 patients, there were no responses. High AGT activity was observed in all four biopsies analyzed.


CONCLUSIONS
Temozolomide is not active against RCC and this clinical observation may be due to high levels of AGT in this tumor.
Park
D K
DK
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Ryan
C W
CW
Dolan
M E
ME
Vogelzang
N J
NJ
Stadler
W M
WM
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000032:analysis; D016879:Salvage Therapy; D016019:Survival Analysis; D000077204:Temozolomide; D017211:Treatment Failure
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide