bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and quality of life (QoL) findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5-FU/LV + O (FOLFOX-6) in metastatic colorectal cancer (MCRC)
Authors: Hebbar M. , Bennouna J. , Boige V. , Ychou M. , Lledo G. , Adenis A. , Faroux R. , Rebischung C. , Douillard J. , Conroy T. 
Published: March 2020

4099 Background: A recent phase III trial in first-line MCRC showed that XELOX is non-inferior to infusional 5-FU + oxaliplatin (FOLFOX-4) for progression-free survival (PFS) [Cassidy ESMO 2006]. Here we present safety and QoL findings from a study of XELOX vs. FOLFOX-6 in first-line MCRC. Methods: Between 16 May 03 and 31 Aug 04, 306 patients (pts) were randomized to receive either XELOX (156 pts: × 1,000mg/m2 bid d1–14, O 130mg/m2 d1, q3w) or FOLFOX-6 (150 pts: O 100mg/m2 d1 LV 400mg/m2 2h infusion then 5-FU 400mg/m2 i.v. bolus then 2,400–3,000mg/m2 46h infusion, q2w) for 6 months. Primary objective: demonstrate non inferiority of XELOX in terms of best response rate (RECIST). Secondary objectives: evaluate QoL and pt satisfaction with care by EORTC QLQ-C30 and FACIT (chemotherapy convenience and satisfaction) questionnaires. Pts completed questionnaires at baseline, before cycles 3/4, 6/8 and at final visit in XELOX/FOLFOX-6 arms, respectively. Results: 245 pts (QLQ-C30) and 225 pts (satisfaction) were evaluable for QoL. The compliance rate was >70%. At baseline, QoL scores were not significantly different. QLQ-C30 functional and symptomatic scores were stable in both arms. According to FACIT, there was no difference between arms, although XELOX-treated pts wasted less hours of their free time than those on FOLFOX-6: 10±23 vs. 37±68 hours, respectively (p=0.007). XELOX was a more ‘comfortable’ treatment (p<0.001 vs. FOLFOX-6 at 2nd evaluation and p=0.009 at 3rd evaluation). Safety profile was acceptable in both arms. In the safety population (n=304), XELOX pts had more grade 3/4 hand-foot syndrome (3 vs. 1% p=0.215), thrombocytopenia (12 vs. 5% p=0.052) and diarrhea (12% vs. 7% p=0.1), but less grade 3/4 febrile neutropenia (0 vs. 6% p=0.001) and neuropathy (8 vs. 19% p=0.003) than those on FOLFOX-6. Treatment discontinuation for toxicity was 19% and 23% for XELOX and FOLFOX-6 arms, respectively. Conclusions: XELOX is comparable to FOLFOX-6 in terms of QoL with less time wasted receiving XELOX. XELOX is also non-inferior to FOLFOX-6 (primary endpoint met/presented at same meeting) with a similar safety profile in first-line MCRC. No significant financial relationships to disclose.
Outcomes differences for African Americans and Caucasians treated with bevacizumab, FOLFOX4 or the combination in patients with metastatic colorectal cancer (MCRC): Results from the Eastern Cooperative Oncology Group Study E3200
Authors: Catalano P. J. , Mitchell E. P. , Giantonio B. J. , Meropol N. J. , Benson A. B. 
Published: March 2020

4100 Background: The relationship between race and clinical outcomes with systemic chemotherapy in patients with metastatic colorectal cancer is uncertain. E3200 is a large, randomized, multicenter phase III trial that demonstrated a gain in overall survival (OS), progression free survival (PFS) and response (RR) for the addition of bevacizumab to FOLFOX4 in previously treated patients with MCRC. We analyzed outcomes for African Americans and Caucasian patients enrolled in E3200. Methods: Patients enrolled in E3200 were randomized to one of three treatments: FOLFOX4, bevacizumab, or the combination. OS, PFS, RR and cycles of chemotherapy were examined as a function of race in 779 patients. Demographic information including race was collected by data management personnel at study sites and reported at registration. Results: There were no differences noted for Caucasians and African Americans with regards to: disease extent, performance status, gender, prior therapy and age distribution (not shown). Outcomes by race are tabulated. Conclusion: These results suggest outcomes differences based on race in the treatment of patients with MCRC. Additional studies are required to elucidate the cause for the observed variation. [Table: see text] No significant financial relationships to disclose.
Tissue factor promoter polymorphism as a prognostic factor in patients with metastatic colon cancer
Authors: Yang D. , Schultheis A. M. , Lurje G. , Iqbal S. , Chang H. , Zhang W. , Groshen S. , Gordon M. , Nagashima F. , Lenz H. 
Published: March 2020

4108 Background: Tissue Factor (TF), a transmembrane glycoprotein, initiates the physiologic coagulation cascade. Cumulative evidence implies that TF plays a key role in tumor angiogenesis. Elevated TF expression has been reported to be associated with poor survival in patients in solid tumor. We investigated whether a functional TF promoter polymorphism -603 A/G is a prognostic factor in patients with advanced colon cancer because the G allele had been linked to high constitutive TF gene expression in human monocytes in healthy volunteers. Methods: 318 patients with metastatic colon cancer treated at the USC/Norris Comprehensive Cancer Center or the LA County/USC Medical Center during 1992 through 2003 were included in this study. Genomic DNA was extracted from white blood cells of peripheral blood samples using the QiaAmp kit (Qiagen, Valencia, CA). The TF polymorphism was genotyped by PCR-RFLP-based approach. The association between the TF polymorphism and overall survival was examined using the log-rank and trend test. The association between TF polymorphism and baseline demographic characteristics was tested using the χ2 test or Fisher’s exact test when appropriate. Results: There were 141 females and 177 males, with a median age of 58 years (range 25–86). The cohort comprised 234 whites, 43 Asians, 15 Blacks, 24 Hispanics, and 2 Native Americans. The median survival was 13.7 months with a median follow-up of 2.3 years. Asians were less likely to bear the G allele compared to other racial groups (P < 0.001, Fisher’s exact test). Patients who carried 1 or 2 G alleles were at higher risk of poor survival compared to patients with no G alleles (A/A) (P = 0.038, trend test). The median overall survival was 14.7 vs. 11.9 months for patients with A/A vs. patients with G/G or A/G, respectively. Conclusions: This study suggests that TF may be a prognostic factor for patients with metastatic colon cancer. The finding should be validated with future prospective clinical studies. No significant financial relationships to disclose.
Serum matrilysin (MMP7) levels are associated with progression, in curatively resected colorectal cancer (CRC) patients
Authors: Martinez-Fernandez A. , Pineda E. , Visa L. , Garcia-Albeniz X. , Auge J. , Nadal C. , Castells A. , Lacy A. , Maurel J. 
Published: March 2020

4124 Background: Matrilysin (MMP7) has been shown to be over-expressed in CRC, specially in liver metastases. Additionally MMP7 over-expression in primary tumor, predict metastatic potential in early-stage disease (Gut 12:1751;2005). As the activated pro-domain, could be detected in serum by ELISA method, we search if it could also identify a subgroup of non-metastatic CRC patients with a higher risk of relapse. Methods: Serum MMP7 (S-MMP7) was measured by commercially available ELISA, in 92 healthy controls and 175 consecutive patients before undergoing laparoscopy-assisted or open curative resection for CRC, between July 2003 to December 2004. Clinic- pathologic variables were tested for their effect on disease-free survival (DFS) in univariate and multivariate Cox regression analysis. Results: S-MMP7 levels were significantly higher in CRC patients than in controls (p=0.02). Mean age in CRC patients was 71 years (range 31–90). Median nodal retrieval was 14 (range 0–47). The median S-MMP7 (4.9 ng/ml) was chosen for cut-off value. After a median follow- up of 26 months, the rate of DFS was 72%. Univariate analysis identified high S-MMP7 levels, CEA concentration, age, extent of primary tumor and lymph-node metastases as variables associated with DFS. Multivariate analysis identified lymph-node metastases (OR.1,88, p=0.046) and S-MMP7 (OR.1,103, p=0.039) as independent prognostics factors. Conclusions: With a short follow-up, S-MMP7 levels predict recurrence in curatively resected CRC. As a subset of these patients could be managed with secondary liver resection, S-MMP7 determination would be particularly warranted for more intensive surveillance strategies. No significant financial relationships to disclose.
Vascular endothelial growth factor (VEGF) gene polymorphisms associated with prognosis for patients with colorectal cancer
Authors: Chae Y. , Kim J. , Sohn S. , Cho Y. , Moon J. , Jeon S. , Park J. , Lee I. , Choi G. , Jun S. 
Published: March 2020

4125 Background: Vascular endothelial growth factor (VEGF) or its family may be considered to play an important role in lymphangiogenesis and lymphatic tumor spread, thereby affecting prognosis of colorectal cancer. Accordingly, the present study analyzed VEGF gene polymorphisms and their impact on the prognosis for patients with colorectal cancer. Patients and Methods: Four hundred and sixty-five consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tumor tissue and 3 VEGF (-2578C > A, -634G > C, and +936C > T) gene polymorphisms determined using a PCR/DHPLC (Polymerase chain reaction/Denaturing high-performance liquid chromatography) assay. Results: The median age of the patients was 64 years (range, 21–89), and 264 (56.7%) patients had colon cancer and 201 (48.2%) patients rectal cancer. Pathologic stages evaluable (n=464) after surgery were as follows: stage I (n=79, 17.0%), stage II (n=157, 33.8%), stage III (n=157, 33.8%), and stage IV (n=71, 15.3%). Multivariate survival analysis including stage, differentiation, and CEA level showed that survival for patients with the -634CC (overall survival [OS]: hazard ratio [HR]=0.175, P<0.001; progression-free survival [PFS]: HR=0.554, P=0.040) or GC genotype (OS: HR=0.158, P<0.001; PFS: HR=0.630, P=0.044) were better than for patients with the -634GG genotype, whereas the +936TT (OS: HR=65.959, P<0.001; PFS: HR=2.823, P=0.016) or CT genotype (OS: HR=16.116, P<0.001; PFS: HR=3.507, P<0.001) were associated with a worse survival compared to the CC genotype. In haplotype analysis, the -2578A/-634G/+936T haplotype exhibited a significantly worse survival when compared to the wild -2578C/-634G/+936C haplotype (OS: HR=4.670, P<0.001; PFS: HR=3.624, P<0.001). Conclusions: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome. No significant financial relationships to disclose.
EGFR, Cox-2, and EGF polymorphisms associated with progression-free survival of EGFR-expressing metastatic colorectal cancer patients treated with single-agent cetuximab (IMCL-0144)
Authors: Nagashima F. , Zhang W. , Gordon M. , Chang H. M. , Lurje G. , Borucka E. , Yang D. , Ladner R. , Rowinsky E. , Lenz H. J. 
Published: March 2020

4129 Background: A phase II study of cetuximab (IMCL-0144) has shown response rate of 12 % in patients with EGFR expressing metastatic colorectal cancer (mCRC). Recently, we reported that polymorphisms in the EGFR pathway may be useful molecular markers to predict clinical outcome. In this larger study, we tested whether polymorphisms in genes involved in the EGFR and angiogenesis pathway will be associated with clinical outcome. Methods: We analyzed 136 tissue samples from 346 mCRC pts enrolled in the phase II study of cetuximab (IMCL-0144), 133 cases were informative. The response rate in these 133 pts was 10% with a median progression-free survival (PFS) of 1.3 months (95% CI, 1.2 to 1.5) and an overall survival time (OS) of 5.5 months (95% CI, 4.1 to 7.5). Gr3–4 toxicity was observed in 56%. Gene polymorphisms of EGFR, Cox-2, EGF, cyclin D1, fragment c γ receptor 2A (FCGR2A), FCGR3A, VEGF, IL-8 were assessed from gDNA extracted from tissue samples by using PCR-based RFLP technique. Univariate analysis (Fisher’s exact test for response; log-rank test for PFS and OS) was performed to examine associations between polymorphisms and clinical outcome. A classification and regression tree (CART) analysis was used to identify subgroups of patients who were more likely to benefit from cetuximab. Results: Pts with EGFR G497C GA, Cox-2 G-765C CC, EGF A61G GG genotype showed better PFS (p=0.02, 1.8mo. vs. 1.2mo.; p=0.03, 6.9mo. vs. 1.3mo.; p=0.04, 1.4mo. vs. 1.2mo.), respectively. We found trends in associations between Cox-2 and tumor response (p=0.09), between EGF and Gr3–4 toxixity (p=0.06). CART analyses indicated that germline polymorphisms in EGFR, EGF, Cox-2, Cyclin D1, IL-8, FCGR2A and FCGR3A genes could be used to identify patients who benefit most likely of cetuximab therapy. Conclusions: Our data suggest that the polymorphisms of EGFR, Cox-2, and EGF may be useful molecular markers to predict clinical outcome in mCRC pts treated with single-agent cetuximab. And prospective studies will need to be done to confirm these preliminary findings. [Table: see text]
Infusion-related reactions (IRR) associated with cetuximab plus irinotecan treatment in patients with irinotecan-resistant metastatic colorectal cancer (mCRC): Findings from the MABEL study
Authors: Siena S. , Glynne-Jones R. , Thaler J. , Adenis A. , Preusser P. , Aguilar E. Aranda , Aapro M. , Loos A. , Esser R. , Wilke H. 
Published: March 2020

4137 Background: Cetuximab is an IgG1 anti-EGFR monoclonal antibody, active alone and in combination with irinotecan in mCRC patients (pts) who have failed prior irinotecan therapy. In previous studies with cetuximab, IRRs were observed in a small proportion of pts especially at the first infusion. Methods: MABEL investigated cetuximab plus irinotecan in pts with EGFR-detectable mCRC whose last treatment regimen contained irinotecan. A secondary objective of MABEL was to further study cetuximab-related adverse events. Study treatment was cetuximab, initial dose 400 mg/m2, weekly 250 mg/m2, plus irinotecan with dose and schedule as pre-study. Data analyzed included prophylactic pre-medication, IRRs and medication for IRRs. Prophylactic medication given before the first cetuximab infusion was categorized as chlorphenamine antihistamines, antihistamines other than chlorphenamine, and any antihistamines plus corticosteroids. Results: Overall, 1147 pts were treated in this study: median age was 62 years [25–84], Karnofsky performance status was =70% and 64% pts were male. 1,122 patients were pre-treated with antihistamines. The frequency of IRRs was lower in pts who received antihistamines plus corticosteroids than in pts who received antihistamines alone (9.6% vs 25.6% any grade, 1% vs 4.7% grade 3/4 IRRs). The primary efficacy variable of MABEL was the 12-weeks progression-free survival (PFS) status. Efficacy results by pre-medication groups for PFS (see table ) and overall survival do not suggest differences related to prophylactic pre-medication. Conclusions: The data suggest that the type of pre-medication impacts on the occurrence of IRRs, and that the addition of corticosteroids to antihistamines reduces IRRs without altering antitumor efficacy in the analyzed pre-medication groups. [Table: see text] No significant financial relationships to disclose.
A prospective study to evaluate the role of gene expression profiles (GEP) in predicting clinical outcome of patients (pts) receiving preoperative chemotherapy for oesophagogastric (OG) cancer
Authors: Rao S. , Cunningham D. , Benson M. , Te Poele R. , Welsh L. , Starling N. , Norman A. , Saffery C. , Workman P. , Clarke P. 
Published: March 2020

4501 Background: Whilst preoperative chemotherapy has demonstrated survival benefit for pts with potentially resectable OG cancer it is not possible to predict the benefit for an individual pt. This study was designed to prospectively correlate GEP with clinical outcome. Methods: Eligible pts were deemed to have resectable disease after staging CT, EUS, and laparoscopy as indicated & following discussion at the multidisciplinary team meeting. All pts received neoadjuvant platinum & fluoropyrimidine based chemotherapy & clinical data were entered prospectively onto a study specific database. GEP were produced from total RNA isolated from snap frozen pre treatment tumour biopsies obtained at baseline endoscopy. Labelled cDNA was hybridised versus a universal human reference using an in house c DNA array of 22,000 clones. Results: Of the pts with adequate follow up accrued between 2002–2005, 35 met the quality control measures for the arrays. Median age=66 yrs (47–83); male=32, female=3; tumour subsites: oesophagus=23, oesophago-gastric junction (OGJ)=12; adenocarcinoma=35; T stage: T 2=3, T3=30, T4=2; N stage: N0=12, N1=23; performance status 0=7, 1=28. Median follow up=938 days. Median overall survival (OS) = 570 days. Prognostic groups were designated according to the median OS (days) of the group: good > median and poor < median. Supervised hierarchical clustering of normalised data revealed significantly differentially expressed genes based on OS (p<0.01) with 2 distinct clusters: a poor outcome group: N= 17 (2yr OS 17.6%) [95% CI: 4.3–38.3], a good outcome group: N=18 (2 yr OS 55%) [95% CI: 30.5–74.8]. Of the differentially expressed genes, those involved in receptor tyrosine kinase signalling & cell growth were amongst the most significantly affected pathways. Conclusions: This novel technique using GEP in tumour biopsies has successfully identified groups of tumours with distinct gene expression profiles that correlate with survival. The approach warrants further validation in a larger cohort. It could facilitate the development of tailored treatment according to individual tumour biology in OG cancer. No significant financial relationships to disclose.
Individual patient data-based meta-analysis assessing pre-operative chemotherapy in resectable oesophageal carcinoma
Authors: Thirion P. G. , Michiels S. , Le Maître A. , Tierney J. 
Published: March 2020

4512 Background: Optimal management of operable localised oesophageal carcinoma remains to be determined. The debate is fuelled by some positive individual trials showing a benefit of preoperative chemotherapy (CT+S) or preoperative chemo-radiotherapy (CRT+S) over surgery alone (S). Our group has initiated an individual patient data-based meta-analysis to quantify the potential benefit of CT+S over S. Methods: The methodology used for trial identification and data analysis has been previously reported. The primary endpoint was overall survival (OS). The secondary endpoints were disease-free-survival (DFS) analyzed with a 6 months landmark method, tumour resectability (complete resection rate) and post-operative mortality. The logrank-test, stratified by trial, and hazard ratio (HR) were used for comparison. Subgroup analyses by age, sex, performance status, and histologic type were prospectively planned. Results: Twelve eligible randomized trials (2,284 patients) were identified. Individual patient data from 9 trials (2,102 patients) with a median follow-up of 5.3 years were available for the OS analysis. There was a statistically significant OS benefit in favour of CT+S (HR=0.87, 95% CI 0.79–0.95, p=0.003) translating into a 5-year absolute OS increase of 4% (from 16 to 20%). Based on 7 trials (1,849 patients), the HR for DFS was 0.82 (95% CI 0.74–0.91, p=0.001) in favour of CT+S, representing a 5-year absolute DFS benefit of 4% (from 6 to 10%). The complete resection rate across 8 trials (1,933 patients) was significantly greater in the CT+S arm (67%) compared to the S arm (62%) (OR=0.81, 95% CI 0.67–0.98, p=0.03). No difference was seen in postoperative death (6.7%). No interaction between treatment effect and patients characteristics was seen. Conclusions: Individual patient data-based meta-analysis represents the highest level of evidence and this study shows a small but significant overall and disease-free survival benefit in favour of preoperative chemotherapy over surgery alone. Unrestricted grants from LNCC and Sanofi-Aventis. No significant financial relationships to disclose.
A randomized second line trial in patients with gemcitabine refractory advanced pancreatic cancer - CONKO 003
Authors: Riess H. , Pelzer U. , Stieler J. , Schwaner I. , Heil G. , Görner M. , Mölle M. , Hilbig A. , Dörken B. , Oettle H. 
Published: March 2020

4517 Objective: For nearly ten years gemcitabine (G) was standard first line therapy for patients (pts) with advanced pancreatic cancer (APC). There is no consensus about second line therapy after disease progression while receiving G, but 5-FU-based regimens are considered. Results about randomized second line studies in APC are very rare. Our phase II study (ASCO 2002) showed activity of the OFF (oxaliplatin/folinic Acid (FA)/5-fluorouracil (FU) [24h] ) regimen in 23 pts. To examine the impact and the side effects of oxaliplatin we initiated a multicenter phase III study to compare OFF and FF in pts with G refractory APC. Methods: Pts with CT/ MRT confirmed failure with G in first line therapy, Karnofsky Performance Status (KPS) >60%, controlled pain, adequate hematological, renal and liver functions were eligible. Pts were stratified according to duration of first line therapy, KPS and tumor stage. We randomized pts to outpatient treatment with FF (FU 2g/m2 (24h)/ FA 200 mg/m2 (30min) on d1, d8, d15 and d22) or OFF (FF+Oxaliplatin 85mg/m2, d8, d22). In both arms the next cycle started on day 43. Pts were followed with regular staging every 3 months or at any signs of disease progression. Results: Until now we randomized 161 of 165 (planned) pts between 02/2004 and 01/2007. So we expect to present first results (side effects, progression free survival, overall survival) at the meeting. No significant financial relationships to disclose.
Phase II study of docetaxel in combination with oxaliplatin in patients with metastatic or locally advanced esophagogastric cancer previously untreated with chemotherapy for advanced disease. Results of the CECOG-Study ESGAS.1.2.001
Authors: Hejna M. , Zacherl J. , Ba-Ssalamah A. , Püspök A. , Pluschnig U. , Brodowicz T. , Zielinski C. C. , Raderer M. 
Published: March 2020

4527 Background: A phase II trial was performed to determine the antitumor efficacy and tolerance of combined docetaxel and oxaliplatin in previously untreated, advanced patients with gastroesophageal adenocarcinoma. Methods: Thirty-six patients with histologically confirmed advanced gastroesophageal adenocarcinoma were entered in this trial. Treatment consisted of 3-weekly courses of docetaxel 80 mg/m2 and oxaliplatin 100 mg/m2 both given on day 1. A 5-day course of human granulocyte colony stimulating factor (G-CSF) 5 μg/kg/day was given subcutaneously to prevent neutropenia; in addition, if haemoglobin was <12.0 mg/dl, erythropoietin 10,000 IU was administered subcutaneously 3 times per week. Primary objective was to evaluate the time to progression. Results: The confirmed overall response rate was 36%, including 3 complete responses (8.3%) and 10 partial responses (27.7%). Fifteen patients (41.7%) had stable disease and 8 (22.3%) progressed while on treatment. The median time to response was 2.5 months, the median time to progression was 5.3 (1- 33+) months and the median overall survival time was 9.8 (2.5–35+) months with 8 (22%) patients currently alive. Hematologic toxicity was common, though WHO grade 3/4 neutropenia occurred only in 6 (17%) patients and anaemia also in 6 (17%) patients, respectively. Nonhematologic adverse reactions were usually mild to moderate; grade 3 toxicities included emesis, diarrhoea and mucositis each in 1 patient (3%). Conclusion: Our data suggest that the combination of docetaxel and oxaliplatin with G-CSF and erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal adenocarcinoma. No significant financial relationships to disclose.