A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium.
BACKGROUND
Sorafenib is an oral multikinase inhibitor that blocks cell proliferation via the ERK pathway and angiogenesis via the VEGF pathway. This phase II trial was conducted to determine the efficacy and tolerability of sorafenib for the treatment of patients with metastatic urothelial cancer (UC) who had not had prior chemotherapy for advanced disease.


METHODS
Seventeen chemo-naïve UC patients with adequate performance status and organ function were treated with sorafenib 400 mg twice daily on a continuous basis until progression or unacceptable toxicity. The primary endpoint was objective tumor response rate as measured by RECIST criteria. Secondary endpoints included rate of prolonged stable disease (>3 months), time to progression, median and 1 yr survival and safety and tolerability.


RESULTS
There were no objective responses. Only one patient had stable disease by RECIST criteria and remained on treatment more than 3 months. Three patients had stable disease by RECIST criteria but were on treatment less than 3 months due to progressive disease (PD) or adverse events (AE). Eight patients had PD by RECIST criteria as their best overall response. Two patients had symptomatic PD prior to cycle 2 evaluation, and three patients were inevaluable (1 death, 1 AE, 1 withdrew consent).The time to progression was 1.9 months (range 0.7-8.7 months) and median survival was 5.9 months. The most common grade 3+ toxicities were abdominal pain, back pain, hand-foot reaction and bladder infection.


CONCLUSIONS
Sorafenib does not show sufficient activity as a single agent in first-line metastatic urothelial cancer to warrant further investigation.
Sridhar
Srikala S
SS
Princess Margaret Hospital, Phase II Consortium, 610 University Avenue, Suite 5-222, Toronto, Ontario M5G 2M9, Canada. srikala.sridhar@uhn.on.ca
Winquist
Eric
E
Eisen
Andrea
A
Hotte
Sebastien J
SJ
McWhirter
Elaine
E
Tannock
Ian F
IF
Mukherjee
Som D
SD
Wang
Lisa
L
Blattler
Chantale
C
Wright
John J
JJ
Moore
Malcolm J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib