NEW YORK-While only about
15% of patients with renal cell carcinoma
respond to standard treatment
with interferon and interleukin-2, patients
in a phase II trial of the targeted
agent SU011248 showed a response
rate of 35%. The trial involved patients
with metastatic renal cell cancer
for whom standard therapy had failed.
"This early study of SU011248 in
the treatment of renal cancer has shown
more activity as a single agent than any
other drug I've studied in the past 15
years," reported Robert J. Motzer, MD,
of Memorial Sloan-Kettering Cancer
Center in New York (abstract 4500).
SU011248 simultaneously blocks
multiple tumor growth factor receptors,
including vascular endothelial
growth factor receptor (VEGFR),
platelet-derived growth factor receptor
(PDGFR), KIT, and FLT3.
Dr. Motzer and colleagues tested
SU011248 in 63 patients in a singlearm,
multicenter trial. To be eligible,
patients had to have metastatic renal
cell cancer and failed one prior cytokine
therapy. Among those participating,
26 patients had been treated previously
with interferon, 19 with
interleukin-2, and 8 with interferon
plus interleukin-2. Eighty-seven percent
of patients had two or more sites
of metastasis, including 50% with bone
metastases and nearly 20% with liver
metastases. Median age was 60 years,
and the oldest patient was 87.
The treatment regimen was 50 mg
of daily oral SU011248 given in repeated
6-week cycles of 4 weeks treatment,
2 weeks rest. Treatment continued
until disease progression or
toxicity. In 22 patients, the dose was
reduced to 37.5 to 25 mg owing to
grade 3-4 toxicity, primarily including
asymptomatic amylase or lipase elevations.
Patients' response was assessed
using RECIST (Response Evaluation
Criteria in Solid Tumors) criteria. The
primary endpoint was overall response
Dr. Motzer reported that 22 patients
(35%) had partial responses, 22
(35%) had disease stabilization lasting
for more than 3 months, and 19 (30%)
had disease progression. "Very few
patients had overt progression," he
"Fourteen of the partial remissions
remain durable, and patients continue
on treatment (range 5.1+ to 12.0+
months)," Dr. Motzer said. Median
time to progression was 8.3 months.
Probability of survival at 1 year was
65%, and 43 patients are alive with
median follow-up of 10.5 months.
Toxicity included 25% grade 2 fatigue
and 8% grade 3 fatigue. Fatigue
was the only adverse effect that oc-
curred in more than 5% of patients.
"There was no hemorrhage and no
hypertension," Dr. Motzer reported.
Grade 3 or 4 laboratory abnormalities
included 30% grade 3 lymphopenia
without infection, 10% grade 3
neutropenia, and 2% grade 4 neutropenia,
21% elevated lipase, 8% elevated
amylase without clinical signs of
pancreatitis, and 8% fatigue/asthenia.
Two patients were taken off the study
because of decreases in left ventricular
ejection fraction of > 20% without
Time to progression was 8.3
months with SU011248 vs 4.8 months
in historical data with bevacizumab
and 2.5 months with placebo.
"SU011248 was well tolerated when
given once daily by oral administration
on a 4-weeks-on/2-weeks-off
schedule. A high level of antitumor
activity was demonstrated by a 35%
partial response rate. Also, antitumor
activity was suggested by a prolonged
median time to progression of
8.3 months compared to historical
controls," Dr. Motzer said. "The antitumor
effect was demonstrated as a
second-line therapy following cytokine
failure, a setting where no effective
systemic therapy exists."
SU011248 is now in phase III trials
vs interferon for first-line treatment
of advanced kidney cancer and is
also being investigated in a confirmatory
single-arm phase III trial as
second-line therapy, Dr. Motzer told
Oncology News International.