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5011 Background: A prior phase III trial (TARGETs) demonstrated that sorafenib (SOR) doubled median progression-free survival versus placebo in previously treated clear cell renal cell cancer (RCC) patients (pts). The ARCCS trial made SOR available to a broader range of RCC pts through an expanded access program. Methods: This open-label, nonrandomized trial enrolled pts with advanced RCC not eligible for, or without access to, other SOR clinical trials; ECOG PS 0–2 with waivers granted for pts with ECOG PS 3–4; age =15 yrs; and adequate prior treatment of brain metastases. Major exclusion criteria included treatment <4 wks prior, life expectancy <2 mos, uncontrolled hypertension, and severe renal impairment requiring dialysis. Objectives were to analyze the safety and efficacy (response by RECIST) of 400 mg bid SOR in a community-based setting. Enrollment ceased on 12/20/05 when SOR became commercially available in the US, and those with no prior therapy or non-clear cell RCC continued in an extension protocol. Enrollment completed in Canada in 8/06. Results: A total of 2488 pts were valid for safety: 69% male with median age 63 yrs and most (83%) had prior nephrectomy; histologies included 78% clear-cell, 7% papillary, 1% chromophobe, and <1% collecting duct and oncocytoma. Median time from diagnosis for all pts was 1.4 yrs (range <1–34). Of those pts receiving prior therapy (n=1249), treatments included interferon alfa (54%), interleukin 2 (43%), bevacizumab (23%), thalidomide (12%), and sunitinib (2%). Grade 3 and 4 adverse events occurring in > 2% pts were hand- foot skin reaction 7.2%, fatigue 5.3%, hypertension 4.4%, rash/desquamation 4%, dehydration and dyspnea 2.7%, and diarrhea 2.5%. Efficacy assessment, mainly PFS, was limited by the short median time (14 wks) on study due to many pts enrolling during the last 2 months of the study. Of 1,850 pts evaluable for response, 17.5% had unconfirmed PR. One (0.1%), 67 (3.6%), 1479 (79.9%) and 303 (16.4%) had CR, PR, SD, and PD, respectively. Conclusions: ARCCS pts were representative of the broader range of RCC pts in the community including those excluded from previous SOR trials. Toxicity and response rates were similar to those reported previously, supporting the generalizability of the phase III trial data. [Table: see text]

4581 Background: ABT-869 is a novel orally active, potent and selective inhibitor of the vascular endothelial growth factor and platelet derived growth factor families of receptor tyrosine kinases. Results of an interim analysis of a phase 2 trial of ABT-869 in HCC are presented. Methods: An open-label, multicenter phase II trial (M06–879) of oral ABT-869 at 0.25 mg/kg daily in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity, is ongoing. Key eligibility criteria included unresectable or metastatic HCC; up to one prior line of systemic treatment; and at least one measurable lesion by computed tomography (CT) scan. The primary endpoint was the progression free (PF) rate at 16 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed centrally and by the investigators; presented results are from central assessment. Results: 44 pts were enrolled from 09/07 to 08/08 at 6 centers internationally, with interim data available for 34 pts. There were 28 C-PA pts (median age, 63.5 y [range, 20- 81]) and 6 C-PB pts (median age, 64.5 y [range, 36–69]) and 73.5% received no prior systemic therapy. For the 19 evaluable C-PA pts included in the per-protocol interim analysis, 8 (42.1%) were progression free at 16 weeks [95% CI 20.3, 66.5]. The estimated ORR was 8.7% [95% CI, 1.1, 28] for the 23 C-PA pts and 0% for the 2 C-PB pts who had at least one post-baseline CT scan reviewed by central imaging. For all 34 pts, median TTP was 112 d [95% CI, 110, -], median PFS was 112 d [95% CI, 61, 168] and median OS was 295 d [95% CI, 182, 333]. The most common adverse events (AEs) for all pts were hypertension (41%), fatigue (47%), diarrhea (38%), rash (35%), proteinuria (24%), vomiting (24%), cough (24%) and oedema peripheral (24%). The most common grade 3/4 AEs for all pts were hypertension (20.6%) and fatigue (11.8%). Most AEs were mild/moderate and reversible with interruption/dose reductions/or discontinuation of ABT-869. Conclusions: ABT-869 appears to benefit HCC patients, with an estimated TTP of 112 days and an acceptable safety profile. Updated results from this ongoing study will be presented. [Table: see text]

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ObjectiveThis phase i study aimed to determine the maximal tolerated dose of cisplatin administered every 2 weeks with infusional 5-fluorouracil (5fu) and concurrent radiation therapy (rt) in patients after complete resection of gastric adenocarcinoma. MethodsPatients with resected stage ib to iv (M0) gastric adenocarcinoma were treated with 12 weeks of infusional 5fu (200 mg/m 2 daily) and with rt (45 Gy in 25 fractions starting on day 16). Cisplatin was administered in escalating doses (0,20, 30, and 40 mg/m 2 ) in weeks 1, 3, 5, and 7. In the final cohort, patients received an additional dose of cisplatin (40 mg/m 2 ) in week 9. ResultsAmong the 34 patients [median age: 56 years (range: 31-77 years)] who were assessable for toxicity, 5 experienced dose-limiting toxicities: 1 sepsis (cohort 1), 1 fatigue (cohort 2), 3 upper gastrointestinal toxicity (1 in cohort 2, 2 in cohort 5). Cohort 5 exceeded the maximal tolerated dose. Median follow-up was 2.5 years (range: 0.3-5 years). The 3-year overall and relapse-free survival rates were 86% and 71% respectively; median survival was not reached. ConclusionsCisplatin was well tolerated in combination with infusional 5fu and rt, showing promising activity in the adjuvant treatment of gastric cancer. Infusional 5fu 200 mg/m 2 daily for 12 weeks with cisplatin 40 mg/m 2 in weeks 1, 3, 5, and 7 and with concurrent rt 45 Gy in 25 fractions, starting at day 16, is being explored in a phase ii study at our institution.