Effect Of An Individualized Dose/Schedule Strategy For Sunitinib In Metastatic Renal Cell Cancer (Mrcc) On Progression-Free Survival (Pfs): Correlation With Dynamic Microbubble Ultrasound (Dce-Us) Data

356 Background: Sunitinib area under the curve (AUC) correlates with response and PFS (Houk et al). Current recommendations for dose modification do not take this into account. Methods: A single center retrospective review identified mRCC patients (pts) where individualized (individ) sunitinib dose/schedule modifications (DSM) were used to maximize dose and minimize time off therapy (Rx). Pts were started on 50 mg 28 days (d) on/14 d off. DSM were done to keep toxicity (fatigue, skin, GI) at ≤ grade-2. DSM-1 was 50 mg 14 d/7 d with individ increases in d on Rx based on toxicity. DSM-2 was 50 mg 7 d/7 d with individ increases in d on Rx. DSM-3 was 37.5 mg continuously with individ 7 d breaks. DSM-4 was 25 mg continuously with individ 7 d breaks. Results: In 171 pts; median age was 60y; 20% good, 60% intermediate, 20% poor prognosis by Heng criteria; 80% had nephrectomy; 79% clear cell histology; 60% were previously untreated. At a median follow-up of 10.7 months (mo), overall median PFS was 7.9 mo. Of 39 pts still on therapy, 37 were on a DSM Rx. Pts were allocated to three groups based on the dose/schedule used for the longest time. The PFS/response% (PR+SD) for each group was 4.4 mo/65.6% (standard 50 mg 28 d/14 d; 43 pts), 8.0 mo/78.2% (DSM-1/DSM-2; 69 pts) and 10.4 mo/81.3% (DSM-3/DSM-4; 59 pts) with improved PFS (p=0.001) in both DSM groups vs. the standard schedule but no difference in response. 30 pts were studied by DCE-US at baseline, and after 7 d and 14 d on Rx or after 14 d and 28 d on Rx. In responding pts, tumor blood volume decreased at d 7 and again at d 14 vs. baseline but was stable or increased at d 28 vs. d 14. A rebound was seen after 14 d off Rx. Conclusions: Based on the U.S. data, previous pharmacokinetic data (steady state at 10-14 d) and this clinical data, starting pts on 50 mg 14 d/7 d followed by individ DSM may be safe and active. This DSM strategy, was associated with a favorable toxicity profile, apparent improvement in PFS and a good PR+SD rate in a group of unselected mRCC pts, warranting confirmation in a prospective trial. Pts that tolerate 50 mg 28 d/14 d with minimum toxicity may need dose escalation and/or less time off therapy to optimize PFS. [Table: see text]