bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vandetanib plus mFOLFOX6 in patients with advanced colorectal cancer (CRC): A randomized, double-blind, placebo-controlled phase II study
Authors: Yang T. S. , Oh D. Y. , Guimbaud R. , Szanto J. , Salek T. , Thurzo L. , Vieitez J. M. , Pover G. M. , Kim T. W. 
Published: August 2020

4084 Background: Vandetanib is a once-daily oral agent that selectively targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. Methods: Eligible patients with advanced CRC and who had previously progressed after an irinotecan- and fluoropyrimidine-containing regimen were randomized 1:1:1 to receive once-daily oral vandetanib (100 or 300 mg) + modified FOLFOX6 (mFOLFOX6) or placebo + mFOLFOX6; mFOLFOX6 was given as standard 14-day treatment cycles (oxaliplatin 85 mg/m2 2-hr and leucovorin 400 mg/m2 2-hr i.v. infusions, followed by 5- fluorouracil [5-FU] 400 mg/mg2 i.v. bolus and 5-FU 2400 mg/m2 46-hr i.v. infusion). The primary objective was to compare the number of patients with a progression event on or before a mandatory tumor assessment visit at data cut-off (∼4 months after last patient randomized). A progression event was defined as the earliest of objective and/or clinical disease progression, or death from any cause. Results: Between March and November 2007, 104 patients (aged 32–81 years) were randomized to receive study treatment ( Table ). At data cut-off on 8 March 2008, there was a greater % of progression events in the vandetanib 100 mg arm compared with placebo (72% [n=23] versus 65% [n=24]; HR=1.21, 2-sided 80% CI 0.82–1.80; 2-sided P=0.53), and also in the vandetanib 300 mg arm compared with placebo (77% [n=27] versus 65% [n=24]; HR=1.41, 2-sided 80% CI 0.96–2.07; 2-sided P=0.25). All except one patient in each group experienced an adverse event (AE) during the study with diarrhea, nausea, thrombocytopenia, and peripheral sensory neuropathy the most commonly reported AEs ( Table ). Neutropenia was the only CTC grade 4 AE to occur in >1 patient in any group (n=2, vandetanib 100 mg arm; n=0, vandetanib 300 mg arm; n=3, placebo arm). Conclusions: In this study of patients with advanced, previously treated CRC, there was no efficacy benefit for vandetanib (100 or 300 mg) + mFOLFOX6 versus placebo + mFOLFOX6. [Table: see text] [Table: see text]
Resectability and agreement between surgeons: Review of CT and MR scan of the CELIM study: (Multicenter randomized trial of cetuximab/FOLFOX versus cetuximab/FOLFIRI in unresectable liver metastases
Authors: Bechstein W. O. , Lang H. , Köhne C. , Parisi F. , Raab H. R. , Frilling A. , Konopke R. , Weitz J. , Stroszczynski C. , Folprecht G. 
Published: August 2020

4091 Background: Liver resection of patients with colorectal cancer liver metastasis (mets) may provide curative therapy. The decision for resection is based on CT- or MRI scans and includes technical aspects (esp. remaining liver tissue) and prognostic factors (i.e. number of metastases). Methods: During two workshops, CT- or MRI scans at baseline (BL) and after 4 months treatment (follow-up, F-U) of CELIM-patients (pts) were presented to surgeons (surg.) who were blinded to each other, the time of investigation (BL or F-U) and clinical data. Scans were allocated to one of the following categories: (1) resection, (2) exploration, (3) borderline resectable (prior chemotherapy preferred) or (4) non-resectable If scans were allocated to category (3) or (4), the reason (technical or poor prognosis) was stated. For evaluation of resectability over time, pts were regarded as resectable according to presented imaging, if ≥ 50% of surg. voted for (1) or (2). Inter-observer variability was evaluated by a reduced model, too: operation (1+2), borderline, primary chemo therapy preferred (3) and non-resectable, chemotherapy (4). Critical disagreements were assumed if ≥1 surg. voted for (4) and ≥ 50% surg. for (1+2) or vice versa. Results: Seven surg. (≥ 5/workshop) participated at the review. A total of 180 scans were reviewed. Both, BL and F-U scans, were available for 75 pts (68% of study pts). During the review, 24 pts changed from ‘non-resectable‘ at BL to ‘resectable‘ at F-U, 5 pts from ‘resectable‘ to ‘non-resectable‘, 29 pts remained ‘non-resectable‘, and 17 pts ‘resectable‘ (19 pts more resectable at F-U; chi-square: p=.021). R0 resection was actually performed in 16/29 pts classified as ‘resectable‘ (55%) and 13/54 pts not classified as ‘resectable‘ (24%) according to presented BL- images. In the full model (6 possibilities), the agreement between surg. was 51.4 %, p<.001. In the clinically more important reduced model, the agreement was 63.5% (p<.001). Critical disagreements were observed in 18 cases (10%). Conclusions: Resectability according to scans increased significantly during the CELIM trial. Regarding the clinical approach, different surgeons had a high degree of agreement. [Table: see text]
Postoperative liver function recovery after hepatic resection for colorectal metastases previously treated with bevacizumab
Authors: Adam R. , Wicherts D. A. , de Haas R. J. , Lévi F. , Paule B. , Azoulay D. , Castaing D. 
Published: August 2020

4093 Background: The influence of bevacizumab on postoperative morbidity in patients with colorectal liver metastases (CLM) submitted to hepatectomy has been evaluated. However, in spite of a potential inhibition of liver regeneration, its impact on postoperative liver function recovery remains unknown. Methods: From July 2005 to December 2007, we evaluated 37 patients treated with bevacizumab prior to hepatectomy. Postoperative evolution of liver function variables was compared with that of 70 bevacizumab-naïve patients. Recorded parameters included prothrombin time, serum aspartate and alanine aminotransferase levels, and serum gamma-glutamyltransferase and total bilirubin levels. Results: Most patients of the bevacizumab group received 1 line of chemotherapy (62% vs 54% in the control group) (P=0.43). Bevacizumab was combined to 5-fluorouracil (5-FU), leucovorin (LV) and irinotecan or 5-FU, LV and oxaliplatin in the last preoperative line, in 57% and 30% of cases, respectively. Patients received a mean total number of 10.4+5.7 and 11.1+6.2 cycles of preoperative chemotherapy in the bevacizumab and control group (P=0.56). The median number of administered bevacizumab cycles was 6 (range: 3–25). Bevacizumab administration was stopped at a median of 7.9 weeks before surgery (range: 3.6–18.0). Major hepatectomies were performed in 41% and 36% of bevacizumab and control patients, respectively (P=0.62). Baseline liver function tests as well as postoperative liver function recovery were similar between patients treated with or without bevacizumab (Table). Postoperative morbidity occurred in 35% of bevacizumab patients and in 43% of control patients (P=0.44). Conclusions: Preoperative bevacizumab treatment has no impact on short-term liver function recovery after hepatic resection for CLM and has no deleterious effect on the incidence of postoperative morbidity. [Table: see text] No significant financial relationships to disclose.
An animal model for chemotherapy-associated steatohepatitis (CASH) and its prevention by the oral administration of fatty acid bile acid conjugate (FABAC)
Authors: Keizman D. , Maimon N. , Ish-Shalom M. , Buchbut D. , Inbar M. , Klein B. , Bernheim J. , Goldiner I. , Leikin- Frenkel A. , Shpigel S. , Konikoff F. 
Published: August 2020

4098 Background: Preoperative chemotherapy (irinotecan and oxaliplatin), used in patients undergoing hepatic resection of colorectal liver metastases, is associated with the development of CASH. This hepatic injury increases the risk of perioperative morbidity and mortality. An animal model for CASH has not yet been described. Fatty acid bile acid conjugates (FABACs) are novel synthetic lipid molecules that were shown to prevent the formation of diet induced fatty liver. The present study was designed to establish an animal model of CASH and to use it to study the effect of FABAC on its occurrence. Methods: C57B1/6 mice were given different doses of intraperitoneally injected oxaliplatin and irinotecan. Once weekly administered oxaliplatin at a dose of 6mg/m2 for a total dose of 24mg/ m2, was best tolerated and most consistently associated with CASH in comparison to higher doses of oxaliplatin or different irinotecan regimens. Thus it was chosen as the induction model for CASH. Subsequently, 32 mice were divided into a control group (no treatment, n=6), oxaliplatin group (n=14), and a CASH prevention group (n=12) treated by oxaliplatin and C20-FABAC (arachidyl-amido-cholanoic acid) at a dose of 150 mg/kg/day administered by gavage. The animals were sacrificed after 28 days. Their livers were homogenized and analyzed for fat content (measured as mg lipid/g liver tissue). Results: There were no significant differences in animal or liver weights between the groups. Liver fat content, was significantly lower (P<0.0001) among the control (51.63 mg/g) and prevention (62.13 mg/g) groups versus the oxaliplatin group (95.35 mg/g). The difference between the control and prevention groups was not significant. To the best of our knowledge this is the first description of a model and a potential preventive treatment for CASH. Conclusions: C57B1/6 mice treated by intraperitoneal injection of weekly oxaliplatin at a dose of 6mg/m2 for a total of 24mg/m2, can be used as a model for CASH. Oral FABAC therapy reduces the development of chemotherapy associated steatohepatitis in animals treated with oxaliplatin. No significant financial relationships to disclose.
Evaluation of the treatment of peritoneal carcinomatosis of colorectal cancer (CRC) with complete cytoreduction and hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) with oxaliplatin: A Belgian multicenter prospective phase II clinical study
Authors: Hompes D. , D’Hoore A. , Van Cutsem E. , Ceelen W. , Peeters M. , Van der Speeten K. , Bertrand C. , Kerger J. , Legendre H. 
Published: August 2020

4101 Background: Up to 25% of patients with metastatic CRC present with peritoneal carcinomatosis (PC) as the only site of metastases. The concept of Complete Cytoreductive Surgery (CCRS) followed by Hyperthermia and Intraperitoneal Chemotherapy (HIPEC) was developed, aiming for locoregional disease control and long-term survival. Methods: This prospective multicentre registry included 48 patients (M/F ratio 17/31) with PC from CRC, who underwent CCRS and HIPEC with oxaliplatin(460mg/m2). In 72.9% of patients the primary tumor had been previously resected. Median PCI (peritoneal cancer index) was 11 [1–22], with a median of 6 [1–11] abdominal regions involved and a median lesion size score of 3 [1–3]. In 11 cases associated lymph nodes (63.6% mesenteric, 27.3% para-aortic) were resected. To obtain CCRS a median of 2 [2–6] organs needed to be resected, with anterior resection in 45.8%, total colectomy in 8.3% and small bowel resection in 12.5% of cases. A median of 1 [0–6] anastomosis was performed per patient, of which one third were low and 82.1% were performed after HIPEC. Eleven ileostomies and 5 colostomies were constructed. Results: Median operation time was 460min.[125–840], with a median blood loss of 475ml [2- 6000]. HIPEC posed few procedural problems. There was no postoperative mortality. Complication rate was 52.1%, with 18 intra- and 17 extra-abdominal complications. Anastomotic leakage occurred in 10.4% of patients, bleeding in 6.3% and prolonged ileus in 22.9%. Median hospital stay was 20 [5–65] days. Occurrence of intra-abdominal complications significantly affected hospital stay (p=0.0012), but no risk factors for occurrence of postoperative complications could be clearly identified. Median follow-up was 22.7 [3.2–55.7] months, with 91.7% 2-year overall survival. Progression-free survival at 2 years is 64.6%, with PC recurrence in 29.2% of patients and other metastatic disease in 25%. Multivariate analysis only retained the CEA-level as a significant prognostic factor (p=0.0065). Conclusions: CCRS followed by HIPEC for PC of colorectal origin is safe and has longer than expected PFS and OS. No significant financial relationships to disclose.
Oral fluoropyrimidines versus 5-fluorouracil for colorectal cancer: Results of a systematic review and meta-analysis
Authors: Sasse A. D. , Sasse E. C. , dos Santos L. V. , Lima J. S. , Nascente C. M. , Saito H. P. , Tariki M. S. , Conceicao V. C. , Carvalho A. M. , Siqueira N. S. 
Published: August 2020

4111 Background: Previous studies showed that continuous intravenous infusion (cIV) of 5-fluorouracil (5FU) is associated with best tumor response in comparison to bolus 5-FU and perhaps, a slight increase of overall survival. There are some non-inferiority trials comparing oral fluoropyrimidines with bolus or cIV of 5FU, but there is still no definitive evidence of equivalence. This systematic review evaluated the efficacy of oral fluoropyrimidines compared to bolus or cIV administration of 5FU in colorectal cancer. Methods: PubMed, EMBASE, CENTRAL and LILACS databases were searched. Eligible studies were randomized trials (RCTs) comparing chemotherapy regimens containing oral fluoropyrimidines (capecitabine, UFT or Tegafur) and 5FU (bolus or cIV) in patients with colorectal cancer. The primary outcome was overall survival (OS). Secondary outcomes included response rate (RR), progression-free survival (PFS) and disease-free-survival (DFS). Hazard Ratio (HR) and Odds Ratio (OR) with fixed effect model were used for meta- analysis and were expressed with 95% confidence intervals (CI). Results: We included results from 20 RCTs, with a total of 14,779 patients. Compared to cIV of 5FU, capecitabine resulted in lower RR (OR 0.82; 95% CI 0.72 to 0.95; p=0.006), shorter PFS (HR 1.09; 95% CI 1.01 to 1.17; p=0.02) and was associated with a non- significant reduction in OS (HR 1.05; 95%CI 0.97 to 1.14; p=0.23). Compared to bolus 5FU, capecitabine resulted in lower RR (OR 0.80; 95% CI 0.65 to 0.98; p=0.004), but similar OS and PFS. Compared to bolus 5FU, the use of other fluoropyrimidines resulted in similar RR, OS and PFS. Conclusions: Oral fluoropyrimidines are equivalent to bolus 5FU in terms of efficacy, but provides less benefit than cIV 5FU. Combination chemotherapy with cIV 5FU remains the first choice for patients with colorectal cancer. [Table: see text]
Phase II study of capecitabine and oxaliplatin with concurrent radiation therapy (XELOX-XRT) for squamous cell carcinoma of the anal canal
Authors: Eng C. , Chang G. J. , Das P. , Rodriguez-Bigas M. , Skibber J. M. , Qiao W. , Rosner G. L. , Ukegbu L. T. , Wolff R. A. , Crane C. H. 
Published: August 2020

4116 Background: Definitive therapy for squamous cell carcinoma (SCC) of the anal canal consists of external beam radiotherapy with concurrent 5-fluorouracil and mitomycin C or cisplatin. This regimen can be toxic but curative in 80–85% of cases with remaining patients requiring salvage surgical resection. The purpose of this study was to evaluate the tolerability and efficacy of XELOX-XRT as definitive treatment for anal cancer. Primary objectives were time to treatment failure and occurrence of treatment-related toxicity. Methods: Patients with histologically proven SCC of the anal canal, AJCC Stage II-IIIB (T2–4 or N+M0), ECOG PS 0–1, HIV-, and no prior therapy were eligible for XELOX-based chemoradiotherapy. Chemotherapy initially consisted of capecitabine (825 mg/m2) BID, M-F and weekly oxaliplatin (50 mg/m2) (Group 1) with subsequent modification to omission of chemotherapy during weeks 3 and 6 (Group 2). Radiation therapy was provided in the following manner: T1 (45 Gy in 25 fractions), T2 (55 Gy in 30 fractions), and T3–4 (59 Gy in 32 fractions). Intensity-modulated radiation therapy (IMRT) was allowed. Interim safety analysis was conducted 3 months after the 10th pt. Patients were followed in a multidisciplinary manner. Response was determined by CT/MRI, digital rectal examination, and proctoscopy. A biopsy was performed for clinical suspicion of residual or progressive disease. Results: Twenty patients were evaluable for toxicity; 17 for response. Five of 11 (45%) patients developed grade 3 treatment-related diarrhea (Group 1). Therefore, the chemotherapy schedule was modified and only 1 of 9 patients in Group 2 developed grade 3 diarrhea. Complete response rates were 90% in Group 1 and 100% in Group 2. One patient in Group 1 developed distant failure. After a median follow-up of 19 months, no patient has developed local recurrence or required salvage resection with colostomy for a colostomy-free rate of 100%. Conclusions: The combination of capecitabine, oxaliplatin, and radiation therapy (XELOX-XRT) is effective for locally advanced squamous cell carcinoma of the anal canal. This trial continues accrual and updated results will be provided. [Table: see text]
Colorectal cancer stem cells: Characterization and functional analysis
Authors: Yeung T. , Wilding J. , Bodmer W. 
Published: August 2020

4124 Background: Cancer stem cells are defined as cells within a tumour that are able to self-renew and differentiate into all cell lineages within that tumour. With our extensive panel of colorectal cell lines, our aims are: 1) To characterise and isolate cancer stem cells based on stem cell markers, morphological appearances and the ability to form multiple lineages; 2) To understand how cancer stem cells drive tumour growth and progression. Methods: 1) Fluorescent Activated Cell Sorting (FACS); 2) In vitro soft agar clonogenic and Matrigel differentiation assays; 3) In vivo tumourigenic NOD/SCID mice assay; 4) Confocal immunofluorescence imaging. Results: 1) A subpopulation of cells can differentiate into crypt-like megacolonies, retaining the ability to self-renew and differentiate. SW1222 cell line forms heterogeneous colonies when single cells are plated in Matrigel. Megacolonies can both self-renew and form terminally differentiated small colonies, whereas small colonies cannot form megacolonies. Megacolonies develop crypt-like structures and increase their expression of differentiation markers (CDX-1, CK-20) over time. Experiments are currently under way to confirm that cells from megacolonies are able to initiate tumours in NOD/SCID mice. Some cell lines retain the ability to differentiate into both neuroendocrine and epithelial lineages. 2) CD44+CD24+ enriches for the cancer stem cell population. Colorectal cancer cell lines HCT116, HT29, LS180, LS174T and SW1222 express both CD44 and CD24. The CD44+CD24+ subpopulation is the most clonogenic. In SW1222, CD44+CD24+ cells enrich for megacolonies and can reform all four CD44/CD24 subpopulations. 3) Hypoxia reduces differentiation, increases stem-like phenotype and enhances clonogenicity. Hypoxia increases the proportion of undifferentiated colorectal cancer cells when plated on Matrigel and increases clonogenicity. Conclusions: 1) Colorectal cancer cell lines contain subpopulations of cells that have the ability to self-renew, differentiate and drive tumour growth, and may be characterised by their cell surface markers and colony morphology. 2) CD44+CD24+ can be used as markers for colorectal cancer stem cells. 3) Hypoxia increases the stem-like phenotype of cancer cells, reduces differentiation and increases clonogenicity. No significant financial relationships to disclose.
“Poker” schedule of weekly alternating 5-fluorouracil, irinotecan, bevacizumab, and oxaliplatin (FIR-B/FOX) in advanced colorectal cancer: A phase II study
Authors: Santomaggio A. , Ricevuto E. , Cannita K. , Bruera G. , Tudini M. , Lanfiuti Baldi P. , Mancini M. , Porzio G. , Marchetti P. , Ficorella C. 
Published: August 2020

4125 Background: Triplet combinations associating antimetabolites with irinotecan (CPT-11) and/or oxaliplatin (OHP) and/or bevacizumab (BEV) show increased activity in same phase III studies vs doublets, with objective responses (OR) between 40% and 60%. Thus we evaluated in a phase II study the addition of BEV to the triplet combination CPT-11/OHP/5-fluorouracil (5-FU) as first line chemotherapy in metastatic colorectal carcinoma (MCC). Methods: Main inclusion criteria: histologically diagnosis of colorectal cancer (CRC) with measurable disease; age 18–75 yrs; adequate bone marrow reserve and renal and hepatic function; no cardiac diseases; no uncontrolled hypertension; no thromboembolic diseases or coagulopathy, no preexisting bleeding diatheses. Treatment schedule: weekly 5-FU 12-h timed-flat-infusion (from 10:00 pm to 10:00 am) 900 mg/m2/d 1–2, 8–9, 15–16 and 22- 23; CPT-11 160 mg/m2 plus BEV 5 mg/kg days 1 and 15; OHP 80 mg/m2 days 8 and 22, every 4 weeks. A Simon two-stage optimal design was planned: power 80%, error probability α 5%, error probability β 20%, P0 50%, P1 70%, sample size 43 pts (I stage 8/15 OR; II stage 26/43 OR). Primary endpoint: OR. Secondary endpoints: time to progression (TTP), overall survival (OS), toxicity and quality of life. Results: Forty-eight pts were enrolled. Median number of cycles per patient was 5 (range 1–9). In the expected 43 pts assessable intent-to-treat (ITT), OR were 84% (α0.05, CI +12): 2 complete and 34 partial responses. In the overall 48 pts, 46 were assessable ITT: OR 80% (α0.05, CI +12), 2 complete and 35 partial responses, 4 stable disease and 5 progression. Median TTP was 12 months (2+-33+), median OS was 25 months (2+-34+), with a median follow-up of 12 months (2–34). Cumulative G3–4 toxicities by pts were: diarrhea 27%, mucositis 6%, hypertension 2%, hypertransaminasemy 2%, neutropenia 10%. No toxic deaths have occurred. Received-DI: CPT-11 84% of projected-DI, OHP 82%, 5-FU 85%, BEV 84%, per pt respectively. 17 pts (35%) had only liver metastasis and R0 resection was performed in 3 pts (18%). Conclusions: “Poker” combination with FIR-B/FOX schedule shows higher activity than triplet combinations. Thus it may be considered as the most active first line treatment of MCC. No significant financial relationships to disclose.