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Early Study Shows 35% Response to SU011248 in Patients With Metastatic Renal Cell Carcinoma

Early Study Shows 35% Response to SU011248 in Patients With Metastatic Renal Cell Carcinoma

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. Failed Prior Cytokine Therapy 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. Limited Overt Progression Patients' response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. The primary endpoint was overall response rate. 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 said. "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 clinical symptoms. Prolonged Time to Progression 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.

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