Background The endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and provides direction towards more effective and less toxic adjuvant treatment strategies for women with endometrial cancer. Primary Objective(s) The RAINBO program of clinical trials will investigate four molecular class-directed adjuvant treatment strategies following surgical resection to either increase cure rates through the addition of novel targeted therapies or safely reduce toxicity and improve quality of life through treatment de-escalation. Study Hypothesis Molecular-directed adjuvant treatment strategies will improve clinical outcomes and reduce toxicity of unwarranted therapies in women with endometrial cancer. The overarching and translational research RAINBO program will advance knowledge of predictive and prognostic (bio)markers that will improve prognostication and treatment allocation. Trial Design The RAINBO program is a platform of four international clinical trials and an overarching research program. The randomized phase III p53abn-RED trial for women with invasive stage I–III p53abn endometrial cancer compares adjuvant chemoradiation followed by olaparib for 2 years with adjuvant chemoradiation alone. The randomized phase III MMRd-GREEN trial for women with stage II (with lymphovascular space invasion (LVSI)) or stage III mismatch repair-deficient (MMRd) endometrial cancer compares adjuvant radiotherapy with concurrent and adjuvant durvalumab for 1 year to radiotherapy alone. The randomized phase III NSMP-ORANGE trial is a treatment de-escalation trial for women with estrogen receptor positive stage II (with LVSI) or stage III no specific molecular profile (NSMP) endometrial cancer comparing radiotherapy followed by progestin for 2 years to adjuvant chemoradiation. The POLEmut-BLUE trial is a phase II trial in which the safety of de-escalation of adjuvant therapy is investigated for women with stage I–III POLEmut endometrial cancer: no adjuvant therapy for lower-risk disease and no adjuvant therapy or radiotherapy alone for higher-risk disease. The overarching RAINBO program will combine data and tumor material of all participants to perform translational research and evaluate molecular class-based adjuvant therapy in terms of efficacy, toxicity, quality of life, and cost-utility. Major Inclusion/Exclusion Criteria Inclusion criteria include a histologically confirmed diagnosis of endometrial cancer treated by hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel lymph node biopsy, with no macroscopic residual disease after surgery and no distant metastases, and molecular classification according to the WHO 2020 algorithm. Primary Endpoint(s) Recurrence-free survival at 3 years in the p53abn-RED, MMRd-GREEN, and NSMP-ORANGE trials and pelvic recurrence at 3 years in the POLEmut-BLUE trial. Sample Size The p53abn-RED trial will include 554 patients, the MMRd-GREEN trial 316, the NSMP-ORANGE trial 600, and the POLEmut-BLUE trial 145 (120 for lower-risk disease and approximately 25 for higher-risk disease). The overarching research program will pool the four sub-trials resulting in a total sample size of around 1600. Estimated Dates for Completing Accrual and Presenting Results The four clinical trials will have different completion dates; main results are expected from 2028. Trial Registration Number The RAINBO program is registered at clinicaltrials.gov (NCT05255653).

Introduction Here we aimed to evaluate the prevalence and prognosis of Lynch Syndrome (LS)-associated endometrial cancer (EC) in relation to sporadic mismatch repair deficient EC (MMRd-EC) in the combined PORTEC-1,-2 and 3 trials comprising 1336 ECs. Methods MMR-status was determined by MMR-immunohistochemistry (MLH1/PMS2/MSH6/MSH2). MMRd-ECs with detected promoter hypermethylation of MLH1 were classified as sporadic (methylated MMRd-EC). For unmethylated MMRd-EC cases tumor and normal tissue next-generation sequencing was performed. ECs with MMR germline mutations were classified as LS-associated (LS MMRd-EC). Unmethylated MMRd-ECs without MMR germline mutations were classified as MMRd-EC due to other causes (other MMRd-EC). Overall and recurrence-free survival were estimated and compared using Kaplan-Meier method and pairwise log-rank test. Results Among the 1336 ECs, 926 were MMR proficient. Of the 410 MMRd-EC, 376 could be fully triaged; 281 (75%) were methylated MMRd-ECs; 37 (10%) LS MMRd-ECs, and 58 (15%) other MMRd-ECs. The overall LS prevalence was 2.8%. Overall 5-year survival for LS MMRd-EC was 89% (95%CI 79–100%; p=0.055), other MMRd-EC 96% (92–100%; p=0.001), both compared to methylated MMRd-EC 79% (74–84%); 5-year recurrence-free survival was 92% (84–100%; p=0.123), 95% (89–100%; p=0.002), compared to 79% (74–84%), respectively. Conclusion The prevalence of LS in the PORTEC EC trial population was 3% and within the MMRd group 10%. LS MMRd-EC seems to have a better overall and recurrence-free survival than sporadic MMRd-EC caused by hypermethylation. Further research into the underlying causes of non-hypermethylated somatic MMRd-EC is ongoing.

Introduction/Background The TCGA molecular classification of endometrial cancer (EC) has proven prognostic impact for patients with intermediate-risk EC. The randomised PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) compared with RT alone for women with high-risk EC (HREC). We evaluated the prognostic significance of the molecular classification in HREC using tissues from consenting PORTEC-3 trial participants. Methodology 423 paraffin-embedded tissue samples (64% of 660 participants) were collected. Through targeted DNA-sequencing for pathogenic POLE-exonuclease domain mutations (EDM) and immunohistochemistry for p53 and mismatch repair (MMR) proteins, the HREC were classified as POLE-ultramutated (POLEmut), p53 mutant staining (p53abn), MMR-deficient (MMRd) or no specific molecular profile (NSMP). The Kaplan-Meier method, log-rank test and Cox's proportional hazard model were used for analysis. Results Molecular analysis was successful in 410 HREC (97% of the 423), identifying 4 molecular subgroups: p53abn (n=92, 22%), POLEmut (n=52, 13%), MMRd (n=137, 33%) and NSMP (n=129, 32%). Five-year recurrence-free survival (RFS) for patients with POLEmut, p53abn, MMRd and NSMP EC was 98%, 50%, 74% and 76%, respectively (p<0.0001), and overall survival was 98%, 55%, 81% and 88% (p<0.0001). Multivariable analysis showed that p53abn was the strongest prognostic factor for decreased survival, while pathogenic POLE EDM was the strongest favourable factor (table 1). Patients with p53abn HREC had significant benefit of combined adjuvant chemotherapy and radiotherapy (5-year RFS with CTRT 61% versus 37% for RT, log-rank p=0.015). Conclusion The molecular classification provides better risk stratification than histopathology alone. Patients with POLEmut HREC have excellent clinical outcome, suggesting these should be classified as low-risk, independent of other pathologic variables. P53abn EC is the strongest predictor of poor clinical outcome, and these patients had significant benefit from added chemotherapy. Molecular characteristics should be incorporated in clinical diagnostics and decision making and future trials should address molecular subgroup-based treatments. Disclosure AL reports receiving advisory board fees from AstraZeneca, Tesaro, Clovis, MSD, Grisdstone, Seattle Genetics, Gamamabs, and Biocad, and travel support paid to her institution from Roche and AstraZeneca. HN reports is the founder of SME Vicinivax and has collaborated with Aduro, TRON & Merck.

Women with high-risk endometrial cancer (HREC) are at increased risk of recurrence. The PORTEC-3 trial investigated the benefit of adjuvant chemotherapy during and after radiation therapy (CTRT) versus pelvic radiation therapy alone (RT) for women with HREC. In the present analysis we updated outcomes, focusing on patterns of recurrence, and survival and on results for serous cancers. Women with HREC (FIGO-stage I grade 3 with deep myometrial invasion and/or LVSI; stage II or III; or serous/ clear cell histology) were randomized (1:1) to CTRT (two cycles of cisplatin 50 mg/m2 in week 1&4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 at 3-week intervals) or RT alone (48.6 Gy in 1.8 Gy fractions). The co-primary endpoints were overall survival (OS) and failure-free survival (FFS). Secondary endpoints vaginal, pelvic, and distant recurrence were analyzed according to first site of recurrence. The Kaplan-Meier method, log-rank test, and Cox regression analysis were used according to intention-to-treat, and competing risk methods for FFS and recurrence. Analysis of the primary endpoints was adjusted for the stratification factors (participating group, lymphadenectomy, stage of cancer and histological type). PORTEC-3 is registered with ISRCTN (ISRCTN14387080) and ClinicalTrials.gov (NCT00411138). Six hundred eighty-six women were enrolled between 2006 and 2013; 26 were excluded for immediate informed consent withdrawal or ineligibility, leaving 660 patients in the final analysis, 330 CTRT and 330 RT. Median follow-up was 72.6 months (IQR 59.9-85.6). 5-year OS was 81.4% vs 76.1% for CTRT vs RT [HR 0.70, 95% CI 0.51-0.97, p=0.034], and 5-year FFS was 76.5% vs 69.1% [HR 0.70, 95% CI 0.52-0.94, p=0.016]. Women with serous cancers had significantly lower OS compared with other histologies (62.0% vs 81.9% at 5 years), while 5-year OS for serous cancer was 71.4% with CTRT vs 52.8% with RT [HR 0.48, 95% CI 0.24-0.96, p=0.037], and 5-year FFS was 59.7% vs 47.9% [HR 0.42, 95% CI 0.22-0.80, p=0.008]. For women with stage III disease an absolute 5-year OS improvement of 10% (HR 0.63, 95% CI 0.41-0.99, p=0.043) and FFS improvement of 12.5% at (HR 0.61 (95% CI 0.42-0.89, p=0.011) was found with CTRT. Distant metastases were the first site of recurrence in the majority of patients, 21.4% (CTRT) vs 29.1% (RT) (p=0.047), and most patients received chemotherapy for recurrence. Survival after recurrence was 1.2 vs 1.4 years (p=0.7). Pelvic control was high in both arms with isolated vaginal or pelvic recurrence in only 1.2%. This updated analysis with median FU of 6 years showed a significantly improved OS and FFS with combined adjuvant chemotherapy and radiation therapy for HREC. The largest improvement was found for women with stage III and/or serous cancers. Shared decision making remains essential to weigh the costs and benefits for individual patients.

Background. The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway.Methods. We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63.Results. About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% C1237-7.27) and 7.48 (95% C13.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed.Conclusion. Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease. 2017 Published by Elsevier Inc.

Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m(2) in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m(2)). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation. Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (j). Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (j = 0.72), lymph-vascular space invasion (j = 0.72) and histological grade (j = 0.70). Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over-or undertreatment, especially when treatment modalities with substantial toxicity are involved. This study is registered with ISRCTN (ISRCTN14387080, www. controlled-trials. com) and with ClinicalTrials. gov (NCT00411138).

646Aneka is an Application Platform-as-a-Service (Aneka PaaS) for Cloud Computing. It acts as a framework for building customized applications and deploying them on either public or private Clouds. One of the key features of Aneka is its support for provisioning resources on different public Cloud providers such as Amazon EC2, Windows Azure and GoGrid. In this chapter, we will present the Aneka platform and its integration with one of the public Cloud infrastructures, Windows Azure, which enables the usage of Windows Azure Compute Service as a resource provider of Aneka PaaS. The integration of the two platforms allows users to leverage the power of Windows Azure Platform for Aneka Cloud Computing, employing a large number of compute instances to run their applications in parallel. Furthermore, customers of the 647Windows Azure platform can benefit from the integration with Aneka …

4592 Background: Until ASCO 2007, the there was no proven systemic therapy for HCC, but dox was used often because of a response rate (RR) of up to 10%. We tested the effects of B, dox and B + dox in HCC cell lines and mouse models and found dox + B to be at least additive compared to dox alone. Methods: Eligible pts had biopsy proven HCC with no prior chemotherapy or hormonal therapy, ECOG PS 0–2, with measurable and biopsiable disease. Pts had adequate bone marrow function (lower levels allowed for splenomegaly), bilirubin ≤ 2.0 mg/dl, Child’s Pugh class A or B cirrhosis, INR ≤ 1.5, no peripheral neuropathy of grade 2 or higher and normal ejection fraction. Primary endpoint is RR. Null hypothesis = 10% RR. 40 pts were planned (37 eligible) to give 91% power to detect RR of 27% (7 responses) with 1-sided significance of 0.07. Secondary endpoints were toxicity, survival (OS) and progression-free survival (PFS). Dox (20 mg/m2 initially, then changed to 15mg/m2 due to heme toxicity) was given days 1, 8 (day 1 dox was omitted in cycle 1) and B (1.3mg/m2) (from NCI/CTEP) was given days 1, 4, 8 and 11 of a 21-day cycle. Serum was analyzed prior to treatment, cycle 1 day 8 and cycle 2 day 8 for changes in chemokines/cytokines (CKS). Results: 42 pts accrued, 39 confirmed eligible: 28 male, 11 female; 27 white, 9 African American, 3 other; PS = 0 :6, PS = 1: 28, PS =2: 5. 1 response (2.3%, 90% CI [0.1%, 11.6%]) was seen. 10 (25.6%) pts had stable disease, 17 pts (43.6%) had progression. The null response rate of 10% was not rejected (one-sided p-value = 0.98). Median OS was 5.7 months (90% CI [4.4, 7.9]) and PFS was 2.4 months (90% CI [2.1, 3.0]). 28/39 had grade (gr) 3 toxicity, 11 had gr 4. Most common toxicities were gr 3 leukocytes (11 pts), gr 3 platelets (8 pts) and gr 4 platelets (8 pts). Gr 3 fatigue occurred in 7 pts and gr 3 diarrhea in 5 pts. CKS evaluations showed changes in serum levels of GROα, MIP-1α, IL-6 and IL-8 in several pts. Conclusions: Dox + B did not show significant activity in HCC. The regimen was generally well-tolerated with mostly hematologic toxicity and no toxic deaths. B caused changes in several CKS levels in pts with HCC. We will analyze the lab data to correlate with clinical efficacy and toxicity prior to the ASCO 2008 meeting. No significant financial relationships to disclose.

4506 Background: The role of radiation therapy (RT) as part of treatment for pancreatic cancer is uncertain in the post-gemcitabine era. The primary endpoint of this trial was to evaluate the impact upon overall survival for the combination of RT plus gemcitabine (G) versus G alone in locally unresectable pancreatic cancer. Methods: Patients (pts) with histologically proven, locally unresectable pancreatic adenocarcinoma, PS <2, without prior chemotherapy or radiation therapy were eligible. Pts were randomized to ARM A: G alone (1,000 mg/m2 weekly x 3 every 4 weeks) for 7 cycles, or ARM B: RT (50.4 GY in 28 fractions) plus G (600 mg/m2 weekly x 6) followed by 5 cycles of G alone (1,000 mg/m2 weekly x 3 every 4 wks). With a planned sample size of 316 eligible pts, the trial was designed to have an 88% power to detect a 50% improvement in median overall survival from 8 to 12 mos (one-sided log-rank test; significance level = 0.025). Pts were stratified by PS (0 vs.1) and weight loss in prior 6 mos (>10% vs. < 10%). Quality of life (using FACT-Hep) was prospectively measured. Results: From April, 2003 to December, 2005, 74 pts were enrolled. The study was closed early because of slow accrual. Three pts were ineligible because of metastatic disease. Five pts not receiving assigned therapy (metastasis noted during RT planning-2; clinical deterioration-2; withdrew consent-1) are included for survival. Grade IV toxicity, principally gastrointestinal and hematologic, was more common in ARM B (5.7% vs 41.2%; p<0.0001). Objective responses were observed in 2.7% (95% CI [0.09%, 14.1%]) and 8.8% (95% CI [1.9%, 23.7%]) in ARM A and ARM B respectively; the corresponding progression free survivals were 6.1 vs. 6.3 mos (p=0.34). All 71eligible pts have now died (early deaths: ARM A-3, ARM B-1). The MST were 9.2 (95% CI [7.8, 11.4]) and 11.0 (95% CI [8.4, 15.5]) mos for the two arms respectively (p=0.044 two sided stratified log-rank test; one-sided p=0.022). Conclusions: Gemcitabine plus radiotherapy has increased, but generally manageable, toxicities compared to chemotherapy alone. Gemcitabine plus involved field RT is associated with an improved overall survival compared to gemcitabine alone for localized, unresectable pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly

4642 Background: Gemcitabine (G) is standard for metastatic pancreatic cancer (PC), with median survivals of 6 months (m). We conducted this randomized phase II trial to determine the activity of this non-G regimen, and whether combining it with cetuximab (C ) was feasible and active. Primary endpoint was response. 50% fall in CA19–9 is examined as a response surrogate in this update because restaging was not performed in 32% of pts; we previously demonstrated 50% fall in CA19–9 to correlate with survival (p=.02). Methods: Pts required histologic confirmation of adenocarcinoma of the pancreas, distant metastases, ECOG PS 0–1, normal. bilirubin, written informed consent, and were randomly assigned to Arm A or B. CT or MR within 4 weeks (wk) was used for tumor measurement. Pts on Arm A received docetaxel 35 mg/m2 and irinotecan 35 mg/m2 weekly x 4 in a 6 wk cycle. Pts on Arm B received the same therapy, with C (400 mg/m2 wk 1, 250 mg/m2 weekly thereafter). Pts not receiving therapeutic anticoagulation received enoxaparin 40 mg per day. Pts were restaged (RECIST) after 2 cycles (12 weeks). Results: In eligible, treated pts (Arm A = 44, Arm B = 43) (EGFR = 97%): Median age Arm A: 60.2, Arm B: 60.6 years. Arm A 55% male, 34% PS 0. Arm B 86% male, 44% PS 0. Mean number of cycles Arm A = 2.8, Arm B = 3.3. Dominant grade ¾ toxicities were neutropenia, nausea, diarrhea. 32% pts were never restaged (related to baseline PS, p =.03). Responses were seen in 4.5%: Arm A (90% CI 1.5%, 18.4%) and 7%, Arm B (90% CI 2.3%, 19.3%). CA19–9 fell 50% from baseline in 30% Arm A, 39% Arm B (p=0.47). Median progression-free survival Arm A 3.9 m, Arm B 4.5 m. Median overall survival (OS), with 89% of pts known to have died, 6.5m in Arm A. With 98% of pts known to have died in Arm B, OS 5.3 m. Median OS for pooled arms was greater for pts with lesser EGFR immunoreactivity than for pts with 3+ staining on > 50% of cells (p= 0.086). Conclusions: Weekly I/D ± C is associated with grade 3/4 neutropenia/diarrhea. The study did not meet the goal of 4 responding pts in either arm; however, the rate of restaging was markedly lower than projected. The surrogate response endpoint of 50% fall in CA19–9 is exploratory: 11 pts in Arm A and 14 in Arm B experienced a 50% decline in CA19–9. Non-G containing therapy is active in metastatic PC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, ImClone Systems, Pfizer, sanofi-aventis Bristol-Myers Squibb, ImClone Systems, Pfizer

4535 Background: Adenocarcinoma of the stomach and gastroesophageal junction (GEJ) is a highly virulent disease and remains a leading cause of death worldwide. Alterations of the ras/raf pathway may contribute to the pathogenesis of the disease. Sorafenib is a potent inhibitor of raf tyrosine kinase and of several receptor tyrosine kinases (RTKs) that are involved in tumor progression (e.g. VEGFR-2, VEGFR-3, PDGFR-β ). The combination of docetaxel and cisplatin is commonly used in the treatment of gastric cancer. This study tested the efficacy and tolerability of combining sorafenib with docetaxel and cisplatin in patients with metastatic or advanced unresectable gastric/GEJ adenocarcinoma. Methods: Sorafenib 400 mg bid orally, docetaxel 75 mg/m2 IV on day 1, cisplatin 75 mg/m2 IV on day 1, administerd on 21 day cycles. Results: Forty-four patients (35 pts [79.5%] with metastatic and 9 pts [20.5%] with locally advanced unresectable disease) were included with median age of 60 (28–86) and M/F of 37/7. The median number of treatment cycles was 4.5 (1–20+). The median PFS was 5.8 months (90% CI [5.4 - 7.2]), and the median OS 14.9 months (90% CI [8.6 - 15.2]). Seventeen pts have shown an objective response (RR 38.6%, 90% CI [26.3%, 52.2%]), including one complete response (CR 2.3%). The most common grade 3 or higher toxicity was neutropenia (26 pts, 90% CI [45.6%, 71.6%]). Two patients died on study with an event attributed to treatment as the ‘probable’ cause (one died from infection but with only mild [grade 1] neutropenia, the other died of GI hemorrhage). Other common grade 3 or higher toxicities were fatigue, anorexia, hand-foot reaction, nausea, diarrhea and dehydration. Conclusions: The results of the combination of sorafenib with docetaxel and cisplatin in metastatic/advanced gastric/GEJ adenocarcinoma are very encouraging. Further phase III study with the combination should be considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer/Onyx, sanofi-aventis sanofi-aventis Bayer, sanofi-aventis

69 Background: E1201 included operable esophageal adenocarcinoma, staged II-IVa by EUS and accrual ended Oct 2004. The primary endpoint was pathologic complete response (pCR), a surrogate endpoint generally associated with survival which did not meet criteria for further study of either arm. Long term survival results are now available. Stratification included clinical/EUS stage and ECOG performance status (PS). Methods: 81 eligible patients (pts) began treatment. Arm A was cisplatin (C) 30mg/m2 and irinotecan (I) 50 mg/m2 on days (d) 1, 8, 22, 29 of 45 Gy RT/5 weeks. Post-op therapy was C 30 mg/m2 and I 65 mg/m2 d 1, 8 q21 days x 3. Arm B therapy was C 30 mg/m2 and paclitaxel (P) 50 mg/m2 1 hour infusion d 1, 8, 15, 22, 29 with RT. Postoperative therapy was C 75 mg/m2 and P 175 mg/m2 day 1 q21 days x 3. Results: In Arm A, 26/39 have died. Median survival (S) is 35 m (months) and the 5, 6, and 7 year S was 46%, 39%, and 35%. In Arm B, 31/42 pts have died (one pt refused follow-up). Median S in arm B is 21 m. The 5, 6, and 7 year S was 27%, 27%, and 23%. Survival by EUS stage strata: For strata 1 (Stages T2N0M0 or T3N0M0), 14/20 have died. Median S is 37 m and 5 year S is 44%. In stage stratum 2 (Stages T1-3N1M0 or T1-3N0-1M1a), 43/61 have died. Median S is 24 m and 5 year S is 34%. For PS Strata: Patients with PS 0, had median S 35 m and 5 year S of 37% whereas for those with PS 1, the outcomes were 20m and 35%. Survival differences for the treatments and for these strata were not statistically significant. Conclusions: Long term survival is similar for both treatment arms and does not appear superior to results achieved with 5FU based regimens. The prognostic importance of the pretreatment strata was not confirmed. These data, along with the reported pCR (15% arm A; 17% arm B) and toxicity data (> =grade 3 during chemo/RT 68% arm A; 65% arm B), may have importance in aiding in the design and interpretation of ongoing and planned phase II trials adding novel agents or treatment approaches to backbones built on variations of these two regimens.