A University of Chicago consortium phase II trial of SB-715992 in advanced renal cell cancer.
BACKGROUND
Advanced renal cell cancer (RCC) continues to have a poor overall prognosis despite new FDA-approved therapies. Although taxane-based therapies are generally ineffective in RCC, research into the role of the von Hippel-Lindau protein has shown an association with microtubule dynamics. Mitotic kinesins are a class of molecular motors that also interact with microtubules and are required for proper mitotic function. SB-715992 is a new agent that inhibits the function of a mitotic kinesin known as kinesin spindle protein and leads to cell death.


METHODS
Twenty patients with previously treated advanced RCC were enrolled on this phase II trial of SB-715992, with response rate as a primary endpoint.


RESULTS
No patients responded with complete or partial remission. Six patients had stable disease, and 1 patient continues on therapy after 12 cycles. Common toxicities included anemia (80%), elevated creatinine (70%), lymphopenia (45%), fatigue (50%), hyperglycemia (50%), and dyspnea (45%). Reported grade 3/4 toxicities included dyspnea, fatigue, neutropenia with skin infection, dizziness, hyperuricemia, and hypertension.


CONCLUSIONS
This dose and schedule of SB-715992 does not appear to have a significant cytotoxic effect for patients with previously treated advanced RCC.
Lee
Richard T
RT
Department of Medicine, Section of Hematology/Oncology, The University of Chicago, IL 60637, USA.
Beekman
Kathleen E
KE
Hussain
Maha
M
Davis
Nancy B
NB
Clark
Joseph I
JI
Thomas
Sachdev P
SP
Nichols
Katherine F
KF
Stadler
Walter M
WM
D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000627:therapeutic use*; D002291:Carcinoma, Papillary / Q000188:drug therapy*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002641:Chicago; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D012449:Safety; D014495:Universities
D001549:Benzamides; D011799:Quinazolines; C508757:ispinesib