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

NEW YORK-While only about15% of patients with renal cell carcinomarespond to standard treatmentwith interferon and interleukin-2, patientsin a phase II trial of the targetedagent SU011248 showed a responserate of 35%. The trial involved patientswith metastatic renal cell cancerfor whom standard therapy had failed."This early study of SU011248 inthe treatment of renal cancer has shownmore activity as a single agent than anyother drug I've studied in the past 15years," reported Robert J. Motzer, MD,of Memorial Sloan-Kettering CancerCenter in New York (abstract 4500).SU011248 simultaneously blocksmultiple tumor growth factor receptors,including vascular endothelialgrowth factor receptor (VEGFR),platelet-derived growth factor receptor(PDGFR), KIT, and FLT3.Failed PriorCytokine TherapyDr. Motzer and colleagues testedSU011248 in 63 patients in a singlearm,multicenter trial. To be eligible,patients had to have metastatic renalcell cancer and failed one prior cytokinetherapy. Among those participating,26 patients had been treated previouslywith interferon, 19 withinterleukin-2, and 8 with interferonplus interleukin-2. Eighty-seven percentof patients had two or more sitesof metastasis, including 50% with bonemetastases and nearly 20% with livermetastases. Median age was 60 years,and the oldest patient was 87.The treatment regimen was 50 mgof daily oral SU011248 given in repeated6-week cycles of 4 weeks treatment,2 weeks rest. Treatment continueduntil disease progression ortoxicity. In 22 patients, the dose wasreduced to 37.5 to 25 mg owing tograde 3-4 toxicity, primarily includingasymptomatic amylase or lipase elevations.Limited OvertProgressionPatients' response was assessedusing RECIST (Response EvaluationCriteria in Solid Tumors) criteria. Theprimary endpoint was overall responserate.Dr. Motzer reported that 22 patients(35%) had partial responses, 22(35%) had disease stabilization lastingfor more than 3 months, and 19 (30%)had disease progression. "Very fewpatients had overt progression," hesaid."Fourteen of the partial remissionsremain durable, and patients continueon treatment (range 5.1+ to 12.0+months)," Dr. Motzer said. Mediantime to progression was 8.3 months.Probability of survival at 1 year was65%, and 43 patients are alive withmedian follow-up of 10.5 months.Toxicity included 25% grade 2 fatigueand 8% grade 3 fatigue. Fatiguewas the only adverse effect that oc-curred in more than 5% of patients."There was no hemorrhage and nohypertension," Dr. Motzer reported.Grade 3 or 4 laboratory abnormalitiesincluded 30% grade 3 lymphopeniawithout infection, 10% grade 3neutropenia, and 2% grade 4 neutropenia,21% elevated lipase, 8% elevatedamylase without clinical signs ofpancreatitis, and 8% fatigue/asthenia.Two patients were taken off the studybecause of decreases in left ventricularejection fraction of > 20% withoutclinical symptoms.Prolonged Timeto ProgressionTime to progression was 8.3months with SU011248 vs 4.8 monthsin historical data with bevacizumaband 2.5 months with placebo."SU011248 was well tolerated whengiven once daily by oral administrationon a 4-weeks-on/2-weeks-offschedule. A high level of antitumoractivity was demonstrated by a 35%partial response rate. Also, antitumoractivity was suggested by a prolongedmedian time to progression of8.3 months compared to historicalcontrols," Dr. Motzer said. "The antitumoreffect was demonstrated as asecond-line therapy following cytokinefailure, a setting where no effectivesystemic therapy exists."SU011248 is now in phase III trialsvs interferon for first-line treatmentof advanced kidney cancer and isalso being investigated in a confirmatorysingle-arm phase III trial assecond-line therapy, Dr. Motzer toldOncology News International.