Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

4576 Background: Evidence suggests that changes in unidimensional measurements (using RECIST criteria) may not accurately reflect actual changes in tumor size, and do not correlate well with other biomarkers of response, tumor progression, or patient outcome. We evaluated changes in tumor volume of target lesions with volumetric CT, and compared them with response assessments derived from RECIST criteria. Methods: We evaluated target lesions, including lymph node, liver, peritoneal and lung metastases in 25 patients with metastatic gastric cancer or gastroespohageal junction adenocarcinoma treated on a phase II clinical trial with irinotecan, cisplatin and bevacizumab. All patients underwent thin-section multidetector CT at baseline and 6-week follow-up for 10 cycles. Target lesions were measured unidimensionally and volumetrically, using validated automated and semiautomated segmentation algorithms. For initial analysis, correlation was made with the RECIST response using a cut-off value of 65% volume change. A ratio of change in RECIST measure to volume measure was calculated at time of maximal clinical response for each patient, as well as for responders versus non-responders. Results: 18 of 25 (72%) patients showed a clinical response. Of these 18 responders, 5, 6, 4, and 3 were identified as responders using RECIST criteria after cycles 1, 2, 3, and 4, respectively. Using a cut-off of 65% volume change, 14 of these responders were indentified after cycle 1, and 4 were identified after cycle 2. Using a cut-off value of 65%, volume measurements identified responders a mean of 50.3 days earlier than did RECIST criteria. There was a statistically significant (p<0.01) change in ratio of volume measurement change to RECIST measurement change for responding versus stable patients. Conclusions: Volumetric change in tumor size appears to predict clinical response earlier than do RECIST criteria in the majority of cases. Changes in volume are more sensitive because they exhibit a wider dynamic range. Ratios of size changes volumetrically appears to better discriminate RECIST responders from those with stable disease. Further work is needed to define the biologically relevant cut-off value for volume change, and to correlate volume change with other biomarkers. No significant financial relationships to disclose.

13521 Background: Cetuximab is a human-murine chimeric monoclonal antibody against EGFR with approximately a 3% reported incidence of severe (≥ grade 3) anaphylactoid reactions. The overwhelming majority of such reactions have been reported with the initial dose of cetuximab. Diphenhydramine (Benedryl)or a related antihistamine is often given as a premedication for cetuximab, however this may cause fatigue or other side effects. Most early clinical trials of cetuximab permitted investigator discretion in use of premedication beyond the initial cetuximab dose. Methods: We obtained an IRB waiver of authorization to review the records of patients treated with cetuximab at Memorial Sloan Kettering Cancer Center for the first year of commercial availability of cetuximb (Feb, 2004 through Feb, 2005). Computerized pharmacy records were reviewed to identify all patients who were treated with cetuximab (outside of a clinical trial) and use of premedication was then evaluated. Records of institutional adverse event reports regarding chemotherapy administration were reviewed, and, any moderate or severe/life-threatening reactions were evaluated for presence or absence of concurrent premedication. Results: As per our institutional guidelines, all patients received 50 mg of diphenhydramine prior to the initial loading dose of cetuximab, and 25 mg of diphenhydramine prior to the second dose. While there was inconsistency in terms of cessation of diphenhydramine, overall a total of 115 patients received one or more doses of cetuximab without premedication. A total of 746 doses of cetuxmab without diphenhydramine premedication were given over this time period. No severe/life-threatening reactions to cetuximab occurred during these doses given without premedication. Conclusions: Omission of diphenhydramine premedication after the initial two doses of cetuximab is our current institutional practice, and appears not to alter the safety profile of cetuximab. Considering the side effects of diphenhydramine, routine long tern use of antihistamine premedication with cetuximab administration does not appear to be warranted. [Table: see text]

4502 Introduction: Preoperative chemotherapy is a standard option for the treatment of locally advanced gastric cancer(GC). FDG-PET scans have been examined to identify early treatment response in esophagus and GEJ adenocarcinoma. We evaluated the utility of an early change in FDG-PET/CT at several time points in predicting response to preoperative chemotherapy in gastric cancer. Methods: 42 pts with locally advanced GC(preoperative stage T2N+M0 or T3–4NanyM0) were treated with CPT 65 mg/m2 and CIS 30mg/m2 on day(d)1 and d8, every 21 days for 4 cycles. FDG-PET/CT scans were performed at baseline, and in FDG avid patients, again on d15 and d35. The primary objective was to demonstrate that a decrease in FDG-SUV discriminates treatment response. Response was defined pathologically based on microscopic inspection for residual cancer cells and fibrosis(Mandard, Cancer 1994). Disease free survival(DFS) and overall survival(OS) were secondary endpoints. Results: Pt characteristics are as follows: median age 59(35–77), KPS 90%(70–100%), 27 male, gastric:GEJ 31:11. Median follow up is 23.3 months, with median DFS 23.8 months(95%CI 14-infinity) and median OS 39.1 months(95%CI 31–39months). Surgical resection occurred at a median of 101 days from study initiation. Pathologic response correlates significantly with DFS(p=0.005) and with OS(p=0.01). Amongst 31 FDG avid pts, a drop in SUV from baseline to d35 significantly predicts pathologic response(p=0.007) and DFS(p=0.01), whereas the change at d15 does not. 45% decrease in SUV at d35 best distinguishes good from poor pathologic response. With this cutoff, median DFS has not been reached(eg.>23.3 months) for patients with good PET response, and is 14.4 months(95%CI 8.3-infinity) for poor PET responders, p=0.03. Conclusions: Following preoperative chemotherapy, pathologic response at the time of resection significantly correlates with DFS and OS. We confirm that FDG-PET/CT response predicts both pathologic response and DFS following preoperative chemotherapy for locally advanced GC, although at d35. An early PET response assessment provides an opportunity to change therapy in non responding patients, and is currently under investigation(supported by ASCO CDA). No significant financial relationships to disclose.