Paclitaxel, carboplatin, and capecitabine (TCX) with and without radiation in locally advanced and metastatic distal esophageal and esophagogastric junction cancer: A single-center retrospective review

197 Background: Toxicities of the active triple-drug DCF regimen (docetaxel, cisplatin and 5-FU) in gastric cancer limit its broad use and general acceptance as first-line therapy. To improve the toxicity profile of triple-drug therapy, distal esophageal and esophagogastric junction (DE-EGJ) poorly differentiated and moderately differentiated adenocarcinoma patients were treated with TCX. This single-center retrospective review is reported for patients treated between 2005 and 2013. Methods: Patients with DE-EGJ adenocarcinoma were treated with capecitabine (850 mg/m2 5 out of 7 or 14 out of 21 days), carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 3 weeks. Those with locally advanced disease received concomitant radiation therapy (50.4 Gy using 3D approach) during the first 2 cycles. Dose reductions (25-50%), delay of therapy and hospitalizations for disease and treatment-related Grades 3/4 toxicities were recorded. Growth factors were prescribed reactively. Kaplan-Meier statistics were used for survival analyses. The institutional tumor registry data provided the historical median survival. Results: Thirty-one males and 3 females (median age 56, range 37-82) with locally advanced (N=17) and metastatic (N=17) disease were included. Median overall survivals are shown below. Two patients were admitted for neutropenic fever and 7 total hospitalizations occurred. Conclusions: A triple-drug combination first-line regimen (TCX) with and without radiation in DE-EGJ cancer is active, and associated with a manageable toxicity profile. The median survival of 15.8 months in patients with metastatic disease treated with TCX compares favorably with the DCF regimen (9.2 mos), the EOX regimen (11.2 mos) as well as institutional historical controls. Our data suggests that future prospective trials evaluating triple-drug regimens in combination with targeted therapy may be feasible in patients with esophageal and gastric adenocarcinoma. [Table: see text

Defining the optimal timing of adjuvant therapy for resected pancreatic cancer: A statewide cancer registry analysis

406 Background: Recent long-term results from the ESPAC-3 trial suggest that while completing adjuvant therapy (AT) is necessary after resection of pancreatic adenocarcinoma (PDAC), early initiation of AT before 8 weeks may not be associated with improved overall survival (OS). The primary aim of this study was to evaluate the impact of early vs. late AT initiation on OS in a statewide population-based analysis. Methods: Among all patients with stage I-III PDAC in the Surveillance Epidemiology and End Results (SEER) - Kentucky Cancer Registry (KCR) from 2004-2012, those undergoing pancreatectomy were stratified by postoperative chemotherapy/radiotherapy delivery and timing. Patients with preoperative therapy, no AT, or postoperative therapy beyond 16 weeks, were excluded. Remaining patients were stratified into 2 groups defined as “early” (<8 weeks) and “late” AT (8-16 weeks). A Cox regression model was created to analyze the impact of AT timing, adjusting for clinicopathologic variables. Results: Of the 4,882 total patients with PDAC, 1,193 (24%) underwent pancreatectomy. Of these, only 364 (30%) received AT within 16 weeks. With median age 65 years (range 20-101), 86% patients were stage II and 76% were node-positive. Median time to AT initiation was 52 days (range 5-111). Timing of AT did not affect OS (median OS: early AT, 19.5 vs. 19.7 mo, late AT, p=0.63). Median OS for stages I, II, and III were 46.1, 19.3, and 8.6 mo, respectively (p<0.001). Poorly/undifferentiated tumors were associated with worse median OS 17.6 vs. 21.3 mo for well/moderately differentiated tumors (p<0.001). Lymph node positivity was associated with worse median OS 18.1 vs. 25.8 mo for node negativity (p<0.001). On multivariate analysis, factors that affected OS included stage (II, HR 2.54, p=0.022; III, HR 5.16, p<0.001), node positivity (HR 1.57, p=0.008), poorly/undifferentiated grade (HR 1.50; p=0.002), but not AT timing. Conclusions: In this SEER-KCR analysis, there was no difference in OS between early and late AT initiation. Despite its proven value, the ideal window for AT initiation remains unknown as tumor biology continues to trump current treatment regimens

Effect of complications after pancreaticoduodenectomy on adjuvant therapy utilization and survival in pancreatic cancer

422 Background: While adjuvant therapy (AT) completion is a necessary component of multimodality therapy for pancreatic adenocarcinoma (PDAC), its timing and utilization can be hindered by complications after pancreaticoduodenectomy (PD). The primary aim of this study was to evaluate the impact of post-PD complications on AT utilization and overall survival (OS). Methods: Patients treated with PD for PDAC at a single institution (2000-2012) were evaluated. Data on 90-day complications were extracted from the electronic medical record with postoperative major complications (PMC) defined as Grade ≥3. Patient records were linked to the Surveillance Epidemiology End Results - Kentucky Cancer Registry for AT and OS data. Early AT required a first dose before 8 weeks, while late was 8-16 weeks. Initiation after 16 weeks was not considered adjuvant. Chi-square statistics, Kaplan-Meier plots, and log-rank tests were used to examine associations among complication status and AT timing, AT utilization, and OS. Results: Of 84 total patients, 54 (64%) received AT (34 [41%] early; 20 [24%] late). Rates of patients with 90-day complications were as follows: 44 (52%) Grade ≥1, 37 (44%) Grade ≥2, and 18 (21%) Grade ≥3. Low-grade (Grades 1-2) complications were not associated with late AT or lack of AT (both p>0.082). However, PMC were associated with lower rates of AT (7/18, 39% with PMC vs. 47/66, 71% without PMC, p=0.011). Even patients who recovered from PMC were less likely to meet the early 8-week window (4/18, 22%, patients with PMC, vs. 30/66, 46%, patients with no PMC, p=0.039). PMC were associated with worse median OS (6.1 mo, 95% confidence interval, CI, 1.6-12.1, vs. 20.8 mo, 95% CI 17.3-23.8, with no PMC, p0.079). Conclusions: In this series,low-grade complications had minimal effects on AT timing, AT utilization, and OS, but PMC were associated with late and decreased AT utilization and negatively impacted OS.These data suggest that strategies to decrease PMC and/or treatment sequencing alternatives to increase multimodality completion rates in high-risk patients may improve oncologic outcomes

Neoadjuvant nab-paclitaxel and gemcitabine (AG) in borderline resectable (BR) or unresectable (UR) locally advanced pancreatic adenocarcinoma (LAPC) in patients ineligible for FOLFIRINOX

328 Background: AG is superior to gemcitabine in patients with advanced pancreas cancer. There are limited data on the use of AG in BR or UR LAPC. Although FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) is an option for such patients, many are not eligible due to age, poor performance status (PS) or comorbidities. Herein, we report our experience with neoadjuvant AG for BR/UR LAPC in patients ineligible for FOLFIRINOX. Methods: In this retrospective series, we included patients with BR/UR LAPC who received neoadjuvant AG. The treatment algorithm included AG for 3-4 months followed by radiation, then re-evaluation for surgery. The published AG regimen doses were modified based on patient tolerance. The primary outcome measure was R0 resection rate. Secondary outcomes were response rate, tolerability, and overall survival (OS). Results: Between 10/2013-9/2015, 20 patients (14 BR, 6 UR) at two institutions were treated with this approach. Median age was 69 years (range 44-90); 11/20 were female; PS ranged from 0-3; 14 patients have completed therapy and 6 remain on treatment. Five were converted to resectability by imaging and subsequently underwent operation; 4 had R0 resections (29% of patients who have finished therapy). To date, 6 patients died from progressive disease (PD), 2 are alive with PD and 12 remain alive on therapy or surveillance. All patients who achieved R0 resections are alive and disease free. The best response to AG was a partial response in 4 patients (20%), stable disease in 11, and progression in 2 with 3 patients still pending re-evaluation. Mean dose intensity was 77% for AG. Toxicities were similar to the published AG regimen. Conclusions: In this small series, both the R0 resection rate and the response rate were at least 20%, despite frequent dose reductions and relatively low dose intensity. Elderly and/or poor PS patients with LAPC have been historically excluded from curative-intent strategies. Our data suggest that these patients may now have a possibility for cure with the use of neoadjuvant AG