bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of oxaliplatin-based adjuvant therapy on post-relapse survival (PRS) in patients with stage III colon cancer: A pooled analysis of individual patient data from four randomized controlled trials.
Authors: Twelves Christopher , Schmoll Hans-Joachim , O'Connell Michael , Cartwright Thomas H. , McKenna Edward , Sun Weijing , Saif Wasif M. , Lee Luen F. , Yothers Greg , Haller Daniel G.
Published: March 2020

3523

Background: Oxaliplatin-based adjuvant therapy is the standard of care for stage III colon cancer; however, its impact on PRS in these patients is unclear. We therefore compared PRS in trials of patients with stage III colon cancer treated with oxaliplatin plus capecitabine (XELOX) or 5-flourouracil (5-FU; FOLFOX) vs. leucovorin/5-FU (LV/5-FU). Methods: Individual patientdata (N = 4,819) from NSABP C-08, XELOXA, X-ACT, and AVANT were pooled and analyzed by XELOX/FOLFOX vs. LV/5-FU; patients treated with bevacizumab were excluded. Hazard ratios (HR) were estimated by Cox regression analyses and multivariate Cox regression analyses controlled for age, gender, T, and N stage. Post-relapse treatment data were collected when available. Results: Patient demographics and disease characteristics (except lymph nodes examined) were well balanced across analytic groups. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) than in XELOXA and X-ACT (83 and 74 months). PRS was very similar for XELOX/FOLFOX and LV/5-FU (HR 0.94, 95% CI, 0.82–1.07; P = .33). Multivariate analyses supported these findings, but showed that PRS was associated with younger age and lower N stage at diagnosis after controlling for gender and T stage. PRS was also comparable for capecitabine or XELOX vs. LV/5-FU or FOLFOX (N = 5,819, HR 1.07, 95% CI, 0.95–1.20; P = .26). Post-relapse therapies were comparable across the two cohorts. Conclusions: Adjuvant chemotherapy regimen did not impact on PRS in patients with stage III colon cancer; however, both N stage and age demonstrated independent effects on PRS. Studies have demonstrated significantly improved disease-free and overall survival for oxaliplatin-based therapy, and our data show that survival is not compromised by worsened PRS at subsequent relapse. [Table: see text]
Smoking status and prognosis in patients with stage III colon cancer: A correlative analysis of NCCTG phase III trial N0147.
Authors: Phipps Amanda I. , Shi Qian , Limburg Paul J. , Nelson Garth D. , Sargent Daniel J. , Newcomb Polly A. , Alberts Steven R.
Published: March 2020

3526

Background: Prior observational studies have suggested that smoking is associated with poorer overall survival after colon cancer (CC) diagnosis. Using data from N0147, a phase III randomized adjuvant trial of patients with stage III CC, we assessed the relationship between smoking status and cancer outcomes (disease-free survival (DFS) and time to recurrence (TTR)), accounting for possible heterogeneity by patient and tumor characteristics. Methods: Patients completed a risk factor questionnaire at baseline prior to randomization to FOLFOX or FOLFOX+cetuximab (N=1968). Information was collected on smoking and other lifestyle factors, including alcohol consumption, body mass index (BMI), and physical activity. Multivariate Cox models assessed the association between smoking history and the primary trial outcome of DFS, as well TTR, adjusting for other lifestyle and clinical factors. The median follow-up was 3.5 years. Results: Overall, 52% of patients were former or current smokers. Compared to never smokers, ever smokers experienced significantly shorter DFS [3-year DFS: 70% vs 74%, hazard ratio (HR)=1.21, 95% confidence interval (CI): 1.02-1.42]. This association persisted after adjusting for age, sex, tumor subsite, number of nodes involved, T-stage, mismatch repair deficiency, BRAF mutation status, performance score, physical activity, BMI, and alcohol consumption (HR=1.23, 95% CI: 1.02-1.49). There was significant interaction in this association by BRAF mutation status (p=0.02): smoking was associated with shorter DFS in BRAF wildtype CC patients (HR=1.25, 95% CI: 1.04-1.51) but not in BRAF mutant CC patients (HR=0.72, 95% CI: 0.47-1.10). Patterns of association with smoking, overall and by BRAF status, were identical in analyses of TTR. Conclusions: Overall, smoking was significantly associated with shorter DFS and TTR in CC patients. These adverse relationships were most evident in patients with BRAF wildtype CC.
BRAF V600 mutant colorectal cancer (CRC) expansion cohort from the phase I/II clinical trial of BRAF inhibitor dabrafenib (GSK2118436) plus MEK inhibitor trametinib (GSK1120212).
Authors: Corcoran Ryan Bruce , Falchook Gerald Steven , Infante Jeffrey R. , Hamid Omid , Messersmith Wells A. , Kwak Eunice Lee , Ryan David P. , Kurzrock Razelle , Brenner Adrienne A , Luan Jennifer , Sun Peng , Allred Alicia J , Little Shonda M , Patel Kiran , Kopetz Scott , Venook Alan Paul
Published: March 2020

3528

Background: BRAF V600 mutations occur in 10-15% of CRC and may predict lack of response to standard chemotherapy and anti-EGFR treatment. There have been no significant recent changes in the treatment of CRC. Novel therapeutic strategies for BRAF mutant CRC are critically needed. To collect preliminary efficacy data, an expansion cohort of 25 BRAF mutant CRC patients (pts) was included in part 2 of a phase I/II study evaluating the combination of dabrafenib (BRAFi) and trametinib (MEKi). Methods: Eligible pts had BRAF V600 mutant CRC, measurable disease per RECIST 1.1, and previous treatment with anti-cancer therapies. Pts were treated with established dose of dabrafenib (150mg BID) and trametinib (2mg QD). Results: Data for 23 pts are available at data cut-off: median age 54 years, 74% female, ECOG performance status 0 (48%) or 1 (52%). 39% had received prior EGFR inhibitor treatment. 74% had received ≥ 2 prior chemotherapy regimens; 48% had ≥ 1 biologic therapy. 48% had ≥ 3 metastatic sites. Three of the 23 pts were non-evaluable at data cut-off as they had not reached the first restaging assessment. Among the 20 evaluable pts, 1 (5%) achieved partial response and 10 (50%) stable disease. Minor responses (>10% to <30% tumor shrinkage) were observed in 4/10 patients (40%) with stable disease. The most frequent adverse events observed in all Part 2 patients who received the same dosing combination (n=75) included pyrexia (65%), fatigue (47%), nausea (44%), chills (41%), vomiting (31%), constipation (28%), diarrhea (24%) and rash (21%). Conclusions: Dabrafenib at 150 mg BID combines safely with trametinib 2 mg QD in this BRAF mutant CRC cohort. Based on the preliminary anti-tumor activity seen, further investigation is warranted in BRAF mutant CRC pts. Updated safety and efficacy data and an analysis of the relationship between efficacy and potential predictive biomarkers, including microsatellite status, PTEN loss, PIK3CA mutation, and total and phosphorylated EFGR levels, will be presented.
Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer.
Authors: O'Neil Bert H. , Cainap Calin , Van Cutsem Eric , Gorbunova Vera A. , Karapetis Christos Stelios , Berlin Jordan , Goldberg Richard M. , Qin Qin , Qian Jiang , Ricker Justin L. , McKee Mark D. , Carlson Dawn M. , Kim Tae Won
Published: March 2020

3532

Background: Linifanib is a potent and selective inhibitor of VEGF/PDGF receptors. This trial assessed the efficacy and safety of mFOLFOX6 in combination with linifanib or bevacizumab as second-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients (pts) with measurable mCRC refractory to 1 prior regimen and ECOG PS 0–1, stratified by prior bevacizumab treatment and radiotherapy, were randomized to receive mFOLFOX6 with bevacizumab 10 mg/kg on day (d) 1 of 14-d cycle (Arm A), mFOLFOX6 with daily linifanib 7.5 mg (Arm B), or mFOLFOX6 with daily linifanib 12.5 mg (Arm C). The primary endpoint was progression-free survival (PFS). Severity of adverse events (AEs) was graded using NCI-CTCAE v3.0. Results: 148 pts were randomized at 45 sites in 14 countries. 32 pts (21.6%) had received prior bevacizumab. PFS and response data are shown below (Table). Median survival (OS) was not reached at median follow up 7.6 months. Palmar-plantar erythrodysesthesia (PPE) was the only Grade 3/4 AE significantly higher on linifanib (high dose, 16.3%) vs. bevacizumab (0%). Rate of any Grade 3+ AE was significantly higher on linifanib vs. bevacizumab.Hypertension rates were 41.7% (Arm A), 40.0% (Arm B), and 36.7% (Arm C). AEs dose-related to linifanib were constipation, proctalgia, stomatitis, fatigue, weight decrease, decreased appetite, and PPE. Conclusions: The addition of linifanib to mFOLFOX6, compared to mFOLFOX6 + bevacizumab, did not provide a PFS advantage for mCRC. OS results will be updated for conference presentation. [Table: see text]
Phase Ib study of dulanermin combined with FOLFIRI (with or without bevacizumab [BV]) in previously treated patients (Pts) with metastatic colorectal cancer (mCRC).
Authors: Kasubhai Saifuddin M. , Bendell Johanna C. , Kozloff Mark , Kapp Amy V. , Ashkenazi Avi , Royer-Joo Stephanie , Portera Chia C.
Published: March 2020

3543

Background: Dulanermin is a recombinant soluble human Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) that activates apoptotic pathways by binding to the pro-apoptotic death receptors DR4 and 5. This is the final update of the study assessing the safety of dulanermin combined with FOLFIRI (± BV) in previously treated mCRC pts. Methods: This was a multicenter, open-label, dose-escalation and cohort expansion study. Dulanermin was administered intravenously in 14-day cycles on Days 1, 2 and 3 at 9 mg/kg or 18 mg/kg, with FOLFIRI (+ BV in pts not previously treated with BV) on Day 1. Dose-limiting toxicity (DLT) was assessed through 2 cycles (28 days). Adverse events (AE) were recorded through all cycles. Response was assessed with RECIST (v1.0). Results: A total of 27 pts received 1-48 cycles (median 10) of dulanermin with FOLFIRI (1 pt received BV). No DLTs were reported and no relationship between dulanermin dose level and AE incidence or severity was detected. The most frequent AEs reported as dulanermin-related were fatigue (37%), anemia (19%), diarrhea, nausea, stomatitis, and weight decreased (15% each). The most frequent Grade ≥3 AEs reported as dulanermin-related were fatigue (15%), anemia, febrile neutropenia and vomiting (7% each). Serious AEs reported as dulanermin-related included: vomiting, dehydration, and febrile neutropenia (1 pt each). Some of these events were reported as related to dulanermin and other study drugs. One pt died on study due to disease progression. Other reasons for discontinuation of study treatment included disease progression (21 pts, 78%), and physician’s decision and pt’s decision (2 pts each, 7%). One pt is still receiving treatment. Among the 27 pts, best responses included 6 (22%) partial responses (5 confirmed, 1 unconfirmed), 17 (63%) stable disease, 3 (11%) progressive disease and 1 (4%) pt with no on-study tumor assessment. Conclusions: The addition of dulanermin to FOLFIRI (± BV) was well tolerated in previously treated mCRC pts. AEs were similar to those previously reported for the chemotherapy alone. Tumor responses were consistent with treatment response to FOLFIRI in this patient population.
A UGT1A1 *28 and *6 genotype-directed phase I study of irinotecan plus infusional leucovorin and 5-fluorouracil (sLV5FU2) in patients with previously untreated metastatic colorectal cancer (mCRC).
Authors: Hong Yong Sang , Kim Kyu-Pyo , Lee Jae-Lyun , Bae Kyun Seop , Kim Ho-Sook , Shin Jae-Gook , Lee Jung Shin , Kim Tae Won
Published: March 2020

3592

Background: We designed a phase I study to determine maximum tolerated dose (MTD) of irinotecan when combined with sLV5FU2 in mCRC patients (pts). Methods: Pts were genotyped for UGT1A1 *28 and *6, and stratified into 3 groups according to the number of defective allele (DA), designated 0 (*1/*1), 1 (*1/*28, *1/*6), and 2 (*28/*28, *6/*6, *6/*28). Within each group, the dose of irinotecan was escalated (table) in combination with fixed dose of sLV5FU2. Plasma drug levels and dose-limiting toxicity (DLT) were evaluated at cycle 1. Results: A total of 43 pts were accrued: 19 for 0 DA, 20 for 1 DA and 4 for 2 DA group. The MTD was estimated as 300 mg/m2/2-week for the 1 DA group with 2 DLTs in the level 3, and the MTD was not reached for the 0 DA group with 1 DLT in the level 4 (table). The mean relative extents of glucuronidation, AUClast ratio of SN-38G to SN-38, were 9.36, 6.81, and 5.09 for the 0, 1, and 2 DA groups, respectively (P=0.017). Of the 43 pts, five pts showed AUClast, SN38 that exceeded 400 ng·h/mL (1.02 umol·h/L) and DLT was observed in 40% (2/5). The overall response rate was 67.4% (95% CI, 51.5-80.9) with 6 complete responses and 23 partial responses. Median progression-free and overall survival was 8.0 months (95% CI, 7.1-8.9) and 25.6 months (95% CI, 23.4-27.7), respectively. Grade 3 or 4 toxicity during all treatment cycles included neutropenia (79% [0 DA]; 90% [1 DA]; 75% [2 DA]), leucopenia (21%; 30%; 0%), febrile neutropenia (0%; 10%; 0%) and diarrhea (0; 5%; 0) per patient. Conclusions: Dose-normalized exposure of SN38 was significantly higher in the 2 DA UGT1A1 group. Higher doses of irinotecan based on UGT1A1 genotyping are feasible when combined with sLV5FU2 in mCRC pts. The recommended dose of irinotecan was 330, 270, 150 mg/m2/2-week for pts with 0, 1, 2 DA based on pharmacokinetic analysis. [Table: see text]
Reappraisal of the risks and benefits of major liver resection in patients with initially unresectable colorectal liver metastases.
Authors: Cauchy Francois , Aussilhou Beatrice , Dokmak Safi , Fuks David , Farges Olivier , Faivre Sandrine J. , Belghiti Jacques
Published: March 2020

3609

Background: Improvements in both surgical technique and efficacy of chemotherapy have increased the rate of resection for patients with initially unresectable colorectal liver metastases (IU-CRLM). We aimed to evaluate the short and long-term outcomes of major hepatectomy for such patients. Methods: From 2000 to 2011, 257 patients underwent major hepatectomy for CRLM. Seventy-eight (30%) of these patients were considered IU and required portal vein occlusion and/or ≥12 cycles or change in induction chemotherapy regimen to achieve resectability. Results: IU patients had respectively more lesions (5.6 vs.3.6, p=0.001), more frequently bilobar (70% vs.50% p=0.008) and synchronous (83.3% vs.70%, p=0.027) than initially resectable (IR) patients. Post-operative mortality (12.8% vs.1.7%, p=0.001) and major complications (46.2% vs.22.3%, p=0.0001) were higher in IU patients. An associated metabolic syndrome (HR 5.2, CI 1.2-21.9, p=0.025), high grade sinusoidal lesions (HR 2.4, CI 1.1-5.8, p=0.044) and the need for vascular reconstruction (HR 6.3, CI 1.2-34.4, p=0.032) were significant risk factors for major morbidity in IU patients. Significantly fewer IU patients received adjuvant chemotherapy in case of major postoperative complications compared to IR patients (47% vs. 83%, p=0.001). Overall 5-year survival was significantly lower in IU than in IR patients (26% vs.55%, p=0.032) and all IU patients had tumor recurrence within 3 years. The absence of adjuvant chemotherapy and tumor size ≥5 cm were the only factors associated with poor survival in multivariate analysis for IU patients. Conclusions: IU-CRLM patients requiring major liver resection displayed higher morbidity and mortality rates than IR ones, therefore compromising both short and long-term outcomes. Multimodal strategy should be reassessed in the presence of metabolic syndrome, sinusoidal lesions or major vascular involvement.
Association of HER2 and IGF1 germline polymorphisms with outcome in metastatic colorectal cancer (mCRC) patients (pts) treated with second-line irinotecan (IR) with or without cetuximab (CB): The EPIC experience.
Authors: Yang Dongyun , Bohanes Pierre Oliver , Zhang Wu , Harbison Christopher , Trifan Ovidiu C. , Ning Yan , Benhaim Leonor , Wakatsuki Takeru , El-Khoueiry Anthony B. , Lenz Heinz-Josef
Published: March 2020

3615

Background: EPIC, a multinational phase III clinical trial with IR + CB vs IR alone in mCRC pts in the second-line setting after failure of FOLFOX demonstrated a benefit for IR+CB in progression-free survival (PFS) and response rate (RR). We evaluated 6 functional germline polymorphisms involved in the IGF1 and HER2 for their potential role as molecular predictors of clinical outcome in pts treated in the EPIC study. Methods: DNA was extracted from all available formalin-fixed paraffin-embedded tumor samples from the EPIC trial. Genotyping was performed using PCR-RFLP assays and 5’ -end [g-33P] ATP’ labeled PCR-protocols. Univariate analysis (Fisher's exact test for RR; log-rank test for PFS and OS) was performed to examine associations between polymorphisms and clinical outcome. Multivariate analysis (Logistic regression or Cox regression model) was conducted to control baseline patient characteristics and treatment. Results: 186 pts with available samples were treated either with IR/CB (arm A, 84 pts) or IR alone (arm B, 102 pts). Median age was 59 yrs (range 34-85yrs) for arm A and 61 yrs (range 25-90 yrs) for arm B. In arm A, 11/84 pts (13%) showed CR or PR, whereas 73/84 (87%) pts had SD or PD. For arm B, 6/102 pts (6%) showed CR or PR, whereas 96/102 pts (94%) had SD or PD. Median PFS for arm A was 3.0 months (95%CI 2.4- 4.1 months) vs 2.7 months (95%CI 2.2-2.9 months) for arm B; median OS was 9.3 months (95%CI 7.1-21.1 months) for arm A vs 12.3 months (95%CI 10.4- 17.9 months) for arm B. KRAS mutation status was not significantly associated with outcome in our patient cohort. We found that HER2 rs 1136201 was significantly associated with response (RR: AA 6.5%, AG 12.5%, and GG 27.3%, Fisher’s exact test p=0.045). IGF1 rs 2946834 was significantly associated with PFS in both univariate and multivariate analyses (median PFS was 2.8 months in patients with CC or CT vs 1.8 months in patients with TT; log-rank p=0.009; Wald test p=0.008). Conclusions: Our study suggests the prognostic value of polymorphisms in the IGF1 and HER2-pathway in mCRC pts treated with IR± CB. Prospective validation of these findings in clinical trials is warranted.
Pharmacogenetic profiling for oxaliplatin-based adjuvant chemotherapy (CT) benefit in stage II-III colon cancer (CC) patients: A GEMCAD study.
Authors: Feliu Jaime , Custodio Ana , Moreno Juan , Aparicio Jorge , Gallego Javier , Yaya Ricardo , Maurel Juan , Fernandez-Martos Carlos , Sánchez Antonio , Calatrava Ana M , Burgos Emilio , Martinez Marín Virginia , De Castro Javier , Barriuso Jorge , Moreno Victor , Hindi Nadia , Madero Rosario , Lapunzina Pablo , Cejas Paloma
Published: March 2020

3618

Background: Identifying molecular biomarkers for tumour recurrence is critical in successfully selecting early-stage CC patients who are more likely to benefit from adjuvant CT. We tested whether single nucleotide polymorphisms (SNP) within genes involved in biological pathways of interest for CC progression and treatment resistance would predict the risk of recurrence in stage II-III CC patients treated with oxaliplatin and fluoropyrimidines-based adjuvant CT. Methods: Genomic DNA was extracted from formalin-fixed paraffin-embedded samples from 202 surgically treated high-risk stage II (29.7%) and stage III (70.29%) CC patients receiving adjuvant CT (25.24% FOLFOX, 74.75% XELOX) from January 2004 to December 2008. Minimum follow-up was 36 months. Genotyping was performed for 62 SNPs in 31 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 stage II-III CC. Results: After a median follow-up of 51.4 months (7-96), 63 patients (31.18%) had experienced a relapse and 31 (15.34%) had died. Three-year disease-free survival (DFS) and overall survival (OS) were 72.2% (+/-0.032) and 89.1% (+/-0.022), respectively. Multivariate analysis showed that the risk of recurrence for patients with the E-selectine rs3917412 G>A G/G genotype was higher than for those with any A allele genotype [relative risk (RR): 2.02, 95% confidence interval (CI): 1.09-3.73, p=0.024]. In haplotype analysis, patients harboring the E-selectine rs3917412 G>A G/G and methylentetrahydrofolate reductase (MTHFR) rs1801133 C>T T/T haplotype had a higher risk of developing tumor recurrence compared to the E-selectine rs3917412 G>A any A and/or MTHFR rs1801133 C>T any C haplotype (RR: 3.39, 95% CI, 1.51-7.62, p=0.003). The ability to predict recurrence of this combined analysis was independently validated in the second cohort (RR: 3.75, 95% CI, 1.32-10.68, p=0.013). Conclusions: E-selectine and MTHFR SNPs were found to be independent prognostic markers for stage II-III CC patients, suggesting that this combined analysis provides additional prognostic information to that offered by clinicopathologic variables.
Comparison of incidence and patterns of recurrence in colon cancer (Cca) treated by sentinel lymph node (SLN) mapping (M) versus conventional surgery.
Authors: Shaik Mohammed Saifullah , Kanaan Mohammed Nawaf , Tesfaye Anteneh A. , Nagpal Sunil , Elfakharany Mohamed , Johnston Gregory , Arora Madan L. , Singh T.Trevor , Eilender David S. , Saha Sukamal
Published: March 2020

3619

Background: Recurrence of Cca patients (pts) depends on the initial stage at diagnosis. SLNM upstages more pts than conventional surgery (Conv. Surg.) for nodal metastasis, this might have an impact on the incidence and pattern of recurrence. Hence comparative study was undertaken for recurrence in Cca pts undergoing SLNM Vs Conv.Surg. Methods: Group (Gp) A pts underwent SLNM with 1% Lymphazurin. The first 1-4 blue nodes were marked as SLNs followed by standard oncologic resection. Gp B pts underwent Conv. Surg. Data was collected for, TNM staging, Recurrence sites and follow up treatment. Minimum follow up of all pts was 12 month, with mean follow up period 44 months for both Gps. Results: There were 357 pts in GpA and 466 pts in GpB. For GpA pts, SLNM was successful in 99.6% of pts with average (Avg.) SLN was 2.8/pts. Avg. no. of LNs in GpA was 15.4/pts vs. 12.8/pt in GpB (p=0.001). For GpA pts, 46% was LN +ve vs 34% in GpB . Excluding T0, Tis and M1 pts at diagnosis, recurrence was calculated for 313 pts in GpA vs. 314 pts in GpB. An overall recurrence was 7.9% in GpA vs 22.2% (p=0.001) in GpB with distant mets being most common in both Gps. Recurrence of LN +ve and LN –ve pts also were significantly lower in GpA vs GpB (Table). The pattern of recurrence between the two Gps is shown in the Table. Conclusions: SLNM upstages significantly more pts in Cca than conv. surg. Even though pattern of recurrence was similar in both Gps, better staging may have resulted in better treatment, reducing the recurrence in SLNM Gp. Hence SLNM may be beneficial for Cca surgery. [Table: see text]
Effect of perioperative complications on recurrence and survival after resection of hepatic colorectal metastases: Analysis of data from a randomized controlled trial.
Authors: Correa-Gallego Camilo , Gonen Mithat , Fischer Mary , Grant Florence , Kemeny Nancy E. , Kingham T. Peter , DeMatteo Ronald P. , Fong Yuman , Allen Peter J , D'Angelica Michael Ian , Jarnagin William R.
Published: March 2020

3620

Background: Perioperative outcomes such as blood loss, transfusions and morbidity have been associated with cancer specific survival, but this is unsupported by prospective data. Methods: Patients were derived from a previously reported prospective randomized trial of acute normovolemic hemodilution (ANH) versus standard management during major hepatectomy. Patients with metastatic colorectal cancer (mCRC) were selected for analysis. Chemotherapy and survival data were obtained from the medical record. Disease extent was measured using a clinical risk scoring (CRS) system. Log-rank test and Cox proportional hazard model were used to evaluate recurrence free (RFS) and overall survival (OS). Results: This trial enrolled 130 patients, 90 of whom had mCRC. Median follow up was 54 m; median age was 53 yr; 56% were men. The CRS was ≥3 in 55% of patients, and 57% had additional extrahepatic procedures. Morbidity and mortality were 33% and 3%. Chemotherapy was split before and after surgery in 70%; 10% received only preoperative and 19% only postoperative treatment, which was initiated after a median time of 6 wks (IQR = 4-7). RFS and OS were 29 and 59 m. On multivariate analysis, (+) resection margin, high CRS and perioperative complications predicted shorter RFS and OS. Delayed initiation of postoperative chemotherapy (≥ 8 wks) while most common in patients with complications (37 vs 12%; p: 0.01), was not a significant predictor of shorter RFS or OS. Randomization (ANH vs standard) was also not significant in this regard. (See Table.) Conclusions: In this prospective randomized cohort, perioperative morbidity was a highly significant independent predictor of cancer specific outcome, associated with but not entirely explained by delayed initiation of chemotherapy. [Table: see text]
Phase II trial evaluating a 12-week regimen of interdigitating FOLFOX chemotherapy plus pelvic chemoradiation for the simultaneous treatment of primary and metastatic rectal cancer.
Authors: Michael Michael , McKendrick Joseph James , Bressel Mathias , Leong Trevor , Cooray Prasad , Heriot Alexander Graham , Steel Malcolme , Chander Sarat , McClure Bev , Ngan Sam
Published: March 2020

3629

Background: Current chemotherapy regimens used during chemoradiation (CRT) are adequate for radiosensitization but suboptimal for systemic control. The aim of this study was to assess tolerability, and local/systemic benefits of new regimen delivering intensive chemotherapy and radical radiotherapy in an interdigitating manner. Methods: Phase II prospective study for patients (pts) with untreated simultaneous symptomatic primary and metastatic rectal cancer. The treatment regimen: 12 weeks long. FOLFOX chemotherapy (oxaliplatin 100mg/m2, leucovorin 200mg/m2, 5-FU 400mg/m2 bolus, all day 1, and 5FU continuous infusion [CI] 2.4 g/m2/46 hours) was given in weeks 1, 6, and 11. Pelvic CRT: 25.2 Gy in 3 weeks, 1.8 Gy/fr, with concurrent oxaliplatin 85mg/m2 day 1 and 5-FU CI 200mg/m2/day given in weeks 3-5, and 8-10. Pts received, in 12 weeks, 3 courses of FOLFOX and pelvic radiation 50.4 Gy with concurrent oxaliplatin/5-FU. All pt were staged with CT, MRI and FDG-PET before and post-treatment. Results: 26 pts treated. The mean age was 61 years, 69% male. Rectal primary MRI stage was T2 4%, T3 81% and T4 15%. Liver and lung metastases were present in 81%, and 35% of pts, respectively: 38% of patients had more than one site of metastatic disease. 24 pts (92%) completed the 12-week treatment regimen. All pts received the planned radiation dose. 65% of pts received the planned number of oxaliplatin courses with 88% of pts receiving at least 75% of the protocol oxaliplatin dose. In this 12-week period, grade 3 toxicities were neutropenia 23%, diarrhoea 15%, and radiation perineal skin reaction 12%. Only grade 4 toxicity was neutropenia: 15%. PET metabolic response (CR+PR) rate for rectal primary was 96%. Overall PET metabolic response rate for metastatic disease was 60% (CR rate 16%). Conclusions: It is thus feasible to deliver intensive chemotherapy and radical radiotherapy in an interdigitating manner to treat both primary and metastatic rectal cancer simultaneously. High completion and response rates are encouraging. This regimen is the subject of a current phase II neoadjuvant trial for resectable rectal cancer (TROG 09.01).
Triplet chemotherapy (TC) with FOLFIRINOX regimen in metastatic colorectal cancer (mCRC): Experience of the Val d’Aurelle Center.
Authors: Samalin Emmanuelle , Loriot Virginie , Thézenas Simon , Assenat Eric , Portales Fabienne , Carrere Sebastien , Rouanet Philippe , Bleuse Jean-Pierre , Quenet Francois , Ychou Marc
Published: March 2020

3633

Background: TC is a treatment option for mCRC to improve the tumor response rate in selected patients (pts) and the conversion rate of initially non-resectable liver metastases. The aim of this study was to evaluate the impact and feasibility of FOLFIRINOX regimen in mCRC pts. Methods: All mCRC pts with non-resectable disease who have received FOLFIRINOX alone or combined with targeted therapies (bevacizumab or cetuximab) from October 2000 to December 2010 were selected for this analysis. Clinical data were collected in a mCRC specific data base and analyzed by the end of 2011. Results: Ninety two pts (52% of men), median age 59 yrs (range: 27-76) were treated with FOLFIRINOX (D1 oxaliplatin 85 mg/m² IV 2H then irinotecan 180 mg/m² IV 90 min and elvorin 200 mg/m², then 5FU 200 mg/m² and 2400 mg/m² by 46H infusion, D1=D15) alone (64%) or combined with cetuximab(30%) or bevacizumab (6%), as 1st-line in 82 pts (89%). Prophyllactic G-CSF was given in 58% of them. Primary tumor was located in colon (58%) or rectum (42%), and 64 (69%) of pts presented with synchronous metastases: liver 100%, lung 40%, peritoneum 17% and nodes 17%. Median number of cures was 8 (range: 1-12). There was 1 toxic death. Grade 3-4 toxicities were: diarrhea 22%, neuropathy 21%, cutaneous 12%, neutropenia 28%, febrile neutropenia 0%, thrombopenia 6%. Objective Response rate according to RECIST criteria was 72% [CI95% 61-81] including 10 pts with complete response (11%). The primary tumor was resected in 70 pts (76%) and 14% had KRAS mutated tumor. Among the pts with liver metastases, 63 (68%) pts were evaluated for secondary resectability by a multidisciplinary committee and 40 pts (43%) had resection achieved (70% R0). Median overall survival was 49 months [CI95%28-62]. Conclusions: These results confirm the feasibility of FOLFIRINOX regimen with or without targeted therapies and its efficacy in terms of response rate and overall survival as 1rst-line treatment in selected mCRC pts.
Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial.
Authors: Hussain Maha , Tangen Catherine M. , Higano Celestia S. , Crawford E. David , Liu Glenn , Wilding George , Prescott Stephen , Akdas Atif , Small Eric Jay , Dawson Nancy Ann , Donnelly Bryan J , Venner Peter , Vaishampayan Ulka N. , Schellhammer Paul F. , Quinn David I. , Raghavan Derek , Vogelzang Nicholas J. , Thompson Ian Murchie
Published: March 2020

4

The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Tivantinib (ARQ 197) versus placebo in patients (Pts) with hepatocellular carcinoma (HCC) who failed one systemic therapy: Results of a randomized controlled phase II trial (RCT).
Authors: Rimassa Lorenza , Porta Camillo , Borbath Ivan , Daniele Bruno , Salvagni Stefania , Van Laethem Jean Luc , Van Vlieberghe Hans , Trojan Jorg , Kolligs Frank T , Weiss Alan , Barahona Nancy , Gasbarrini Antonio , Lencioni Monica , Pande Amitkumar U. , Lamar Maria , Chen Yinpu , Schwartz Brian E. , Abbadessa Giovanni , Santoro Armando
Published: March 2020

4006

Background: Tivantinib (T) is a selective, oral inhibitor of c-Met, the tyrosine kinase receptor for hepatocyte growth factor involved in tumor cell migration, invasion, proliferation and angiogenesis. T has shown promising results in HCC in phase 1 studies as monotherapy and in combination with sorafenib. Methods: This multi-center RCT, enrolled pts with unresectable HCC, 1 failed systemic therapy, ECOG PS <2. Child-Pugh B-C were excluded. Pts were randomized 2:1 to oral T {360 mg bid (A), 240 mg bid (B)} or placebo (P), stratifying by PS and vascular invasion (VI). Treatment continued until disease progression (PD) or unacceptable toxicity. RECIST 1.1 response was evaluated by CT / MRI every 6 weeks. Crossover to open-label T was allowed after PD. Primary endpoint was time to tumor progression (TTP) in the intent-to-treat (ITT) population by central radiology review. Other endpoints included disease control rate (DCR), PFS, OS, efficacy in Met+ (Met ≥ 2+ in >50% of tumor at immunohistochemistry) pts, safety. Results: Characteristics of the 107 enrolled HCC pts (A= 38, B= 33, P= 36) in T/P: 58/28 male; median age 70/68; PS 0 41/21; VI 22/13; Met+ 22/15; Met- 27/13. Dose A was reduced to B in all pts due to G≥3 neutropenia (NEUT) rate. Major TTP, DCR and PFS benefits were obtained in Met+ pts, with preliminary OS trend favoring T (HR=0.47) and no detrimental effect in Met- pts. DCR (95% CI) in T/P was 44 (31-56) / 31(16-48)% for ITT and 50 (28-72) / 20 (4-48)% in Met+ pts. Most common AEs in T were asthenia (26.8%), NEUT (25.4%), low appetite (25.4%); most common drug-related AEs were NEUT (25.4%), anemia (15.5%). Most frequent drug-related serious AE was neutropenic sepsis (4.2%). Efficacy was similar in A / B with less frequent NEUT in B (21.1% / 6.1%). Final OS, PK, biomarker data will be presented. Conclusions: Compared to P, T significantly benefited second-line HCC pts, especially if Met+, with manageable safety profile at 240 mg BID. [Table: see text]
Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal poorly differentiated neuroendocrine carcinoma: The NORDIC NEC study.
Authors: Sorbye Halfdan , Welin Staffan , Langer Seppo W. , Vestermark Lene Weber , Holt Nanna , Osterlund Pia J. , Dueland Svein , Hofsli Eva , Guren Marianne Gronlie , Ohrling Katarina , Birkemeyer Elke , Thiis-Evensen Espen , Biagini Matteo , Gronbaek Henning , Soveri Leena-Maija , Olsen Ingrid Holst , Federspiel Birgitte , Assmus Joerg , Janson Eva Tiensuu , Knigge Ulrich
Published: March 2020

4015

Background: Gastrointestinal poorly differentiated neuroendocrine carcinoma (GI-NEC) are aggressive tumors with Ki-67>20% and usually metastatic at diagnosis. Knowledge about GI-NEC is limited. We retrospectively reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Methods: Epidemiological, biochemical, histopathological, treatment and survival data were registered for advanced GI-NEC patients diagnosed during 2000-2009 at 12 Nordic university hospitals. Results: 305 patients were included. Palliative chemotherapy was given to 252 patients, median survival was 11 months. Response rate to 1st-line chemotherapy was 31%, 33% had stable disease. Ki-67<55% was by ROC analyses the best cut-off value concerning correlation to response rate. Response rate to platinum-based chemotherapy was lower in patients with Ki-67<55% (14% vs.44%, p<0.001). Response rate for 84 patients given 2nd-line chemotherapy was 18%, whereas 33% achieved SD. The most important negative prognostic factors for survival were poor performance status, primary colorectal tumors, and elevated baseline platelets or lactate dehydrogenase (LDH) levels. Patients with Ki-67<55% had longer median survival (15 months) than patients with Ki-67>55% (10 months) (p<0.001). Survival and response rates did not differ between the different platinum chemotherapy schedules (cisplatin-based vs. carboplatin-based) or morphology subtypes. 53 patients received best supportive care only with a median survival of 1 month. Conclusions: This is, to our knowledge, the largest study reporting patient and tumor characteristics, treatment and survival in advanced GI-NEC. Performance status, location of primary tumor and blood levels of platelets and LDH were the strongest prognostic factors for survival. Patients with Ki-67<55% had significantly longer survival than patients with higher Ki-67, but were less responsive to platinum-based chemotherapy. Our data indicate that to consider all GI-NEC as one single disease entity may not be correct.
Correlation of hand-foot skin reaction (HFS) with treatment efficacy in pancreatic cancer (PC) patients (pts) treated with gemcitabine/capecitabine plus erlotinib: A subgroup analysis from the AIO-PK0104 randomized, cross-over phase III trial in advanced PC.
Authors: Haas Michael , Boeck Stefan Hubert , Laubender Ruediger Paul , Modest Dominik Paul , Vehling-Kaiser Ursula , Waldschmidt Dirk , Kettner Erika , Maerten Angela , Winkelmann Cornelia , Klein Stefan , Kojouharoff Georgi , Gauler Thomas C. , Von Weikersthal Ludwig Fischer , Clemens Michael , Geissler Michael , Greten Tim F , Hegewisch-Becker Susanna , Rubanov Oleg , Mansmann Ulrich Robert , Heinemann Volker
Published: March 2020

4023

Background: AIO-PK 0104 investigated the efficacy and safety of gemcitabine/erlotinib (G/E) followed by capecitabine (C) vs. C/E followed by G. The present subgroup analysis evaluated the correlation between C-associated skin toxicity and outcome parameters in PC. Methods: Within this multicenter phase III trial, pts with confirmed advanced PC were randomly assigned to 1st-line treatment with either C (2,000 mg/m2/d, d1-14 q d21) plus E (150 mg/d, arm A) or G (1,000 mg/m2 over 30 min weekly x 7, then d1, 8, 15 q d28) plus E (150 mg/d, arm B). A cross-over to either G (arm A) or C (arm B) was performed after treatment failure (e. g. disease progression or unacceptable toxicity). Time to treatment failure after 1st- and 2nd-line therapy (TTF2) was the primary study endpoint. Treatment-related skin toxicity was evaluated separately for each treatment arm/each regimen based on NCI-CTCv2. Results: Of 279 eligible pts, 47 had locally advanced, 232 had metastatic disease and 141 pts received second-line chemotherapy. For the present subgroup analysis data on skin toxicity were available from 255 pts. For the 73 pts (29%) with a HFS (any grade documented at any time during the treatment strategy), TTF2 and OS both were significantly prolonged compared to pts without HFS (7.4 vs 4.0 months, p<0.001 and 9.7 vs 5.5 months, p=0.002, respectively). Considering HFS during 1st-line treatment in 123 pts within the CE arm, these results could be confirmed for the 47 pts (38%) with a documented HFS of any grade (TTF2: 7.6 vs. 3.2 months, p<0.001; OS: 10.2 vs. 4.4 months, p=0.001). In pts receiving 1st-line treatment with G/E (n=132) no difference in outcome was observed for pts with (n=13) or without (n=119) HFS of any grade (TTF2: 5.7 vs. 4.2 months, p=0.375; OS: 8.4 vs. 6.6 months, p=0.505). Conclusions: The current subgroup analysis of AIO-PK0104 supports the assumption of a correlation between HFS in PC pts treated with capecitabine or capecitabine/erlotinib and efficacy endpoints like TTF2 and OS. A capecitabin-associated HFS thus might be predictive for efficacy in patients with advanced PC.
A randomized phase II study of continuous versus intermittent S-1 plus oxaliplatin in first-line treatment of patients with metastatic gastric carcinoma.
Authors: Park Sook Ryun , Park Young-Iee , Rhee Jiyoung , Nam Byung-Ho , Kong Sun-Young , Kim Sung Hyun , Choi Mihee , Choi Il Ju , Kim Chan Gyoo , Lee Jong Yeul , Cho Soo-Jeong , Kim Young Woo , Ryu Keun Won , Lee Jun Ho , Kim Noe Kyeong
Published: March 2020

4028

Background: We conducted a randomized phase II study to compare continuous vs. intermittent S-1 + oxaliplatin (SOX) after induction of 6 cycles of SOX in patients (pts) with metastatic gastric cancer (MGC). Methods: Pts >18 yrs with chemo-naive MGC, normal organ function, ECOG PS 0-2, and measurable or evaluable lesion(s) were initially given an induction treatment of 6 cycles of SOX (S-1 40 mg/m2 bid on D1-14 + oxaliplatin 130 mg/m2 on D1 q 3 wks). Pts with CR/PR or SD were randomized to continue SOX (arm A) until progression/intolerable toxicity or discontinue until progression when SOX was re-administered (arm B). The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate, safety, quality of life, and biomarker correlative studies. Results: From July 2007 to Dec 2010, a total of 250 pts entered into the study. Median age was 53 yrs (range, 24-69); PS 0/1/2=13/219/18; M/F=162/88. Three pts did not receive treatment and 126 (50.4%) discontinued treatment before or at the completion of 6 cycles of SOX due to progression (45.6%), pt refusal (2.8%), or adverse events (2.0%). A total of 121 pts were randomized: 59 (48.8%) to arm A and 62 (51.2%) to arm B. Clinical characteristics were well balanced between arms. SOX continuation resulted in a significant reduction in the risk of progression (median PFS, 10.5 months for arm A vs. 7.2 months for arm B; HR=0.57, 95% CI 0.39-0.84, p=0.005). With a median follow-up of 34.0 months (range, 10.5-53.3 months), there was no significant difference in OS (median OS, 22.6 months for arm A vs. 22.7 months for arm B; HR, 0.79, 95% CI 0.51-1.25, p=0.31). Arm A had higher rates of grade 3/4 fatigue (28.8% vs. 8.1%, p=0.004) and neuropathy (25.4% vs. 8.1%, p=0.014) but other grade 3/4 hematologic (neutropenia, 35.6% vs. 32.3%; thrombocytopenia, 23.7% vs. 21.0%; anemia, 15.3% vs. 6.5%) or non-hematologic toxicity rates were not significantly different. Conclusions: Continuous chemotherapy with SOX after induction therapy improved PFS but not OS. Supported by NCC Grant 1010180 (S-1 and oxaliplatin was provided by JEIL Pharm. Co., Ltd. and sanofi-aventis Korea Co., Ltd., respectively).
Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).
Authors: Malka David , Fartoux Laetitia , Rousseau Vanessa , Trarbach Tanja , Boucher Eveline , De La Fouchardiere Christelle , Faivre Sandrine J. , Viret Frédéric , Blanc Jean-Frédéric , Assenat Eric , Hammel Pascal , Louvet Christophe , von Wichert Goetz , Ducreux Michel , Rosmorduc Olivier , Pignon Jean-Pierre , Greten Tim F
Published: March 2020

4032

Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]
Multicenter phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in pancreatic neuroendocrine tumor (PNET): Results of a planned interim efficacy analysis.
Authors: Hobday Timothy J. , Qin Rui , Reidy Diane Lauren , Moore Malcolm J. , Strosberg Jonathan R. , Kaubisch Andreas , Shah Manisha H. , Kindler Hedy Lee , Lenz Heinz-Josef , Chen Helen , Erlichman Charles
Published: March 2020

4047

Background: PNET has long had few effective therapies other than chemotherapy. Recent placebo-controlled phase III trials of the mTOR inhibitor everolimus and the VEGF/ PDGF receptor inhibitor sunitinib noted improved progression-free survival (PFS). However, objective response rates (RR) with these agents are still <10%. Preclinical studies suggest enhanced anti-tumor effects with combined mTOR and VEGF targeted therapy. Methods: We conducted a phase II trial of the mTOR inhibitor TEM (25 mg IV q week) and the VEGF-A monoclonal antibody BEV (10 mg/kg IV q 2 weeks) in patients (pts) with well or moderately differentiated PNET and progressive disease by RECIST within 7 months of study entry. Co-primary endpoints were RR and 6-month PFS. Planned enrollment is 50 patients, with interim analysis for futility after the first 25 evaluable pts. Pts had no prior mTOR or VEGF targeted agents, ECOG PS 0-1, and adequate hematologic and organ function. Continued octreotide was allowed, but not required. Prior interferon, embolization, and ≤ 2 chemotherapy regimens were allowed. Results: Confirmed PR was documented in 13 of the first 25 (52%) evaluable patients. 21 of 25 (84%) patients were progression-free at 6 months. Both endpoints exceeded the protocol-defined criteria to continue enrollment. For 36 evaluable patients, the most common grade 3-4 adverse events attributed to therapy were hypertension (14%), leukopenia (11%), lymphopenia (11%), hyperglycemia (11%), mucositis (8%), hypokalemia (8%), and fatigue (8%). Conclusions: The combination of TEM/BEV has substantial activity in a multi-center phase II trial with RR of 52%, well in excess of single targeted agents in PNET. 6-month PFS was a notable 84% in a population of patients with RECIST criteria progression within 7 months of study entry. Accrual is ongoing.
A phase I study of nab-paclitaxel (A), gemcitabine (GEM), and capecitabine (X) in patients with metastatic pancreatic adenocarcinoma (MPA).
Authors: Truong Thach-Giao , Tempero Margaret A. , Kantoff Emily , Jones Kimberly , Dito Elizabeth , Ong Anna , Ko Andrew H.
Published: March 2020

4048

Background: GEM-based doublets, such as GEM + capecitabine (X), may be beneficial in select pts with MPA. Given preclinical evidence of synergy when a taxane is added to GEM + X, as well as recent phase I/II study results showing substantial activity with GEM + nab-paclitaxel (A) (ORR of 48%, median OS > 12 mos at MTD), we conducted a phase I study evaluating the 3-drug combination of A, GEM, and X (AGX) given biweekly in pts with MPA. Methods: Pts with previously untreated MPA and ECOG PS 0-1 were eligible. A (100-150 mg/m2) and GEM (750-1000 mg/m2 at 10 mg/m2/min) were both administered on day 4, and X (500-1000 mg/m2 bid) on days 1-7, of each 14-day cycle. A 3+3 dose escalation design was used, with expanded cohort at MTD. Primary objective was to establish MTD of this regimen; secondary objectives include safety and preliminary assessment of efficacy. DLT definitions: gr 3-4 ANC or neutropenic fever; gr 4 plts; gr 2-4 hand-foot syndrome (HFS), neuropathy or diarrhea; or other gr 3-4 non-heme toxicity. Results: Fifteen patients were enrolled across two dose levels (age range, 45-74 y). Final MTD was established at dose level 0, consisting of A 100 mg/m2, GEM 750 mg/m2, and X 750 mg/m2 bid. At dose level 1, two of 4 pts experienced DLTs (gr 3 LFT elevation, gr 3 ANC). For the entire study cohort, 10 pts (67%) experienced at least one gr 3-4 AE, including LFTs (20%), N/V (13%), and fatigue (7%). Gr 3-4 heme toxicity was uncommon. Other notable AEs (any grade): fatigue (87%), rash/HFS (67%), N/V (53%), diarrhea (40%), neuropathy (33%). Median # cycles received = 4 (range, 2-16). 73% of pts d/c’ed study treatment due to disease progression. Best response for the entire cohort (n=14 evaluable pts): 2 PR, 8 SD, 4 PD (disease control rate = 71%). Of 12 pts with elevated CA19-9 at baseline, 5 (42%) had >50% biomarker decline. Conclusions: Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of GEM (1000 mg/m2) + A (125 mg/m2). The modest activity seen with this AGX regimen may have resulted from suboptimal dosing, and suggests that dose intensity may be an important factor when trying to incorporate nab-paclitaxel into multidrug regimens.