A phase II trial of intra-patient dose-escalated sorafenib in patients (pts) with metastatic renal cell cancer (MRCC)

Abstract

5026 Background: Sorafenib has demonstrated activity with limited toxicity at a dose of 400 mg bid in MRCC pts. This presents an opportunity to explore a more intensive drug administration. This study allowed individual pt titration designed to evaluate the ability for pts to dose escalate. Response rate (RR), time to progression (TTP) and overall survival (OS) will be assessed. Methods: Eligibility included; pathologic diagnosis of a component of clear cell, progressive measurable MRCC, no more than 1 prior therapy, karnofsky performance status (KPS) = 70%, adequate organ/marrow function and no active CNS involvement. Initial dose 400 mg bid, daily. Dose escalation defined in the table below: Re-evaluation is performed every 8 weeks. RECIST criteria is utilized. Results: 46 patients have been enrolled. 44 are evaluable. 37 male/7 female, median age 50 years (43–79). 19 pts received prior therapy. 39 pts had a KPS of 100%, 5/90%. Sites of disease included; lung, nodal, liver, bone, adrenal, pancreas and kidney. 26 pts 1 metastatic site, 12 /2, 6/3 or more. 22 pts continue to receive sorafenib therapy; 2/800 mg, 7/1,200 mg, and 13/1,600 mg. 8 pts complete response (CR), 14 pts/partial response (PR) and 14 pts stable for 3+ months. Median duration of therapy is 6+ (range 0.2+ - 12+) months. 2 pts have not been reevaluated. Treatment related adverse events to-date; hand/foot syndrome, skin rash, diarrhea, alopecia, fatigue, hypertension, hypophosphatemia, and elevated amylase/lipase. Conclusion: 91% of pts were escalated to 1,200 mg or 1,600 mg per day. Dose escalated sorafenib has promising anti-tumor activity in pts with MRCC as demonstrated by a 52% CR/PR rate. Anti-tumor activity is further suggested by prolonged TTP = 3 months for 33% of pts. Independent radiology review is in progress. Intra-patient dose escalation data in association with anti-tumor activity and toxicity will be presented. [Table: see text] [Table: see text]