bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bi-weekly administration of capecitabine + oxaliplatin (Xelox-2) in first-line treatment of advanced colorectal cancer (ACRC): A phase II study of the Gruppo Oncologico dell’Italia Meridionale (GOIM)
Authors: Fedele P. , Di Maggio G. , Leo S. , Nanni L. , Giuliani F. , Biglietto M. , Lorusso V. , Cinieri S. , Colucci G. , Maiello E. 
Published: August 2020

e15066 Introduction: FOLFOX regimen represents a standard first-line therapy for ACRC pts. Oral capecitabine (XEL) has been shown to be a convenient and well tolerated alternative to intravenous 5-fluorouracil (5-FU) in the treatment of ACRC. Experimental data demonstrated the synergism of XEL with Oxaliplatin (OHP), but the questions about the most appropriate dosage and schedule of capecitabine have not yet been completely resolved. Taking into account these data the GOIM started a phase II study to evaluate the activity and the toxicity of biweekly administration of XEL plus OHP (XELOX-2) in ACRC pts. Methods: Previously untreated pts with histological diagnosis of metastatic colorectal cancer, measurable disease, ECOG PS<2, and age 18–75 yrs entered into this trial. The schedule of treatment was as follows: OHP at 100 mg/mq i.v. on days 1 and XEL at 2,000 mg/mq p.o. in two daily administrations from the 1 to the 7 day, every 2 weeks. RECIST and NCI criteria were employed to determine the activity and the toxicity of this regimen. Results: Fifty-one pts have been enrolled and up to now forty-seven are evaluable for activity and toxicity. The main characteristics of the entered pts were: sex (M/F) 38/13, median age 66,5 yrs (range 54–75 yrs), 28 (55%) single and 23 (45%) multiple site of disease. The main site of disease were liver in 38 pts (75%), lymph-nodes in 17 (33%), lung in 9 (18%). Two CR (4%) and 22 PR (47%), 13 SD (28%) and 10 PD (21%) were observed, with an overall response rate of 51% and a disease control rate (CR+PR+SD) of 79%. Median TTP was 5+ months (range 2–19). A total of 413 cycles were administered. In the evaluable pts the main toxicity rate (G1- 2 vs G3–4) were as follows: thrombocytopenia 51/6, anemia 42/0, neutropenia 15/0, nausea/vomiting 30/2, diarrhea 19/2, neurotoxicity 57/0 and asthenia 30/2. Only one pts presented G4 toxicity (diarrhea). Conclusions: These preliminary data show that the combination of XEL and OHP with a biweekly administration is active and well tolerated in ACRC pts. No significant financial relationships to disclose.
Bevacizumab (Bev), irinotecan (IRI), folinic acid (FA), and 5-fluorouracil (FU) every 2 weeks (BIFF regimen) as first-line treatment for metastatic colorectal cancer (MCRC) patients (pts): The SICOG experience
Authors: Comella P. , Massidda B. , Natale D. , Filippelli G. , Farris A. , Condemi G. , Palmeri S. , Tafuto S. , Vessia G. , Barberis G. 
Published: August 2020

e15067 Background: The IRIFAFU regimen produced in MCRC pts a consistent activity (RR, 33% [95% CI, 27–39%], PFS, 7.4 [95% CI, 6.5–8.3] mo.) in 2 consecutive randomized SICOG trials . Bev was proven to significantly improve the efficacy of IFL regimen. Here we report the safety and activity results of the BIFF regimen as first-line treatment of MCRC. Patients: From Feb 2007 to Jul 2008, 95 pts with MCRC were treated: so far, 85 pts were evaluated for safety: M/F were 47/38, median age (range) was 64 (35–78) yrs. Fifty-six pts had a colon, and 29 pts a rectal carcinoma. ECOG PS was 0 (63 pts, 74%), or 1 (22 pts, 26%). Thirty-four (40%) pts had 1 site, 33 (39%) 2 sites, and 18 (21%) pts ≥3 sites of disease. Liver was involved in 66 (78%), lung in 23 (24%) pts. Twenty-one (25%) pts had an unresected primary (colon 13, rectum 8). Bev 5 mg/kg (1-h), and IRI 180 mg/sqm (1-h) were given IV on day 1, 6S-FA 250 mg/sqm (2-h), and FU 850 mg/sqm (bolus) were given IV on day 2 biweekly for a maximum of 12 cycles. Bev was continued until progression, severe toxicity, or refusal. Results: A median of 9 (range, 1–12) cycles of BIFF were delivered. G4 hematologic toxicity was: neutropenia (21%), and febrile neutropenia (10%). G≥3 non-hematologic toxicity was: diarrhea 15%, vomiting 7%, stomatitis 4%, hypertension 1%. No severe episodes of bleeding were registered. Among 81 assessable pts, 5 CRs (3 in liver, 1 in liver & nodes, 1 in liver & lung), and 41 PRs were registered, giving a RR of 57% (95% CI, 45–68%). Overall, 71/81 (88%, 95% CI, 77–93%) pts obtained a disease control. Liver mets resection, or primary resection, was safely performed in 3 pts and in 2 pts, respectively. After a median follow- up of 12 (range, 6–24) mo., median FFS was 8.4 (95% CI, 6.8–10.0), and median PFS was 14.1 (95% CI, 9.6–18.6) mo. With only 14 deaths, OS results are still immature. Conclusions: Unexpected side effects of the BIFF regimen were not registered. Addition of Bev increased the activity without worsening the tolerability of IRIFAFU combination as compared with our previous experience. Efficacy of BIFF was comparable with that reported with other Bev plus IRI-based combinations. Updated follow-up will be presented. No significant financial relationships to disclose.
Predictors of adjuvant chemotherapy (AT) decision-making in referred patients (pts) with stage II and III colon cancer (CC)
Authors: Ksienski D. S. , Levesque M. , Gill S. 
Published: August 2020

e15070 Background: Randomized clinical trials have demonstrated a robust survival benefit of AT for node positive (stage III) CC patients; similar evidence for node-negative (stage II) patients is lacking. While guidelines recommend AT for stage III colon cancer but AT is not a routine recommendation for stage II. Actual practice of the evidence varies and suggests the interplay of additional variables. We sought to identify factors associated with practice patterns which vary from conventional AT guidelines, ie no AT in stage III CC and receipt of AT in.stage II CC. Methods: Data pertaining to pt demographics, tumor characteristics, and treatment for pts with resected stage II (n=176) and III CC (n=235) referred to the British Columbia Cancer Agency in 2004 was collected by retrospective chart review. One-sided Fisher's exact test was used to assess statistical significance (p<0.05) by univariate analysis. Results: 28% (n=49) of stage II pts received AT. Compared to untreated pts, stage II pts who received AT were significantly more often younger than 66 years (57% vs 21%), lived in a city with a regional cancer center (71% vs 51%), had T4 disease (33% vs 9%), vascular invasion (22% vs 5%), perineural invasion (10% vs 2%) and high grade (26% vs 2%). Marital status, ethnicity, lymphatic invasion and high CEA were not associated with AT in stage II. 29% (n=69) of stage III pts did not receive AT. Compared to treated pts, stage III pts who did not receive AT were significantly more often older than 65 years (91% vs 51%), had low grade disease (96% vs 84%) and presented for oncology consultation greater than 42 days from surgery (29% vs 11%). Marital status, ethnicity, residence, T4 status or N2 status were not associated with no AT in stage III. Conclusions: For pts with stage II CC, subgroups associated with high risk for relapse were more likely to receive AT although the majority of stage II pts in this cohort remained untreated. For stage III disease, almost one-third of referred pts did not receive AT. Older age and delayed presentation were strongly associated with failure to receive AT. Within the limitations of a retrospective review, these data highlight the significant and commonly observed implications of factors other than stage in AT decision-making for high risk resected CC. No significant financial relationships to disclose.
Palliative first-line treatment with weekly high-dose 5-fluorouracil and sodium folinic acid (s-FA) (AIO-schedule) as 24h-infusion plus biweekly oxaliplatin (ox) in patients with definitively non-resectable metastatic colorectal cancer (CRC) following secondary (sec.) metastatic resection: An interdisciplinary phase II trial
Authors: Albrecht H. , Boxberger F. , Wolff K. , Ostermeier N. , Reulbach U. , Maennlein G. , Meyer T. , Hohenberger W. , Hahn E. G. , Wein A. 
Published: August 2020

e15073 Background: In an interdisciplinary phase II trial performed from 1995 to 1997 and based on a 5-FU monotherapy it was possible to achieve both a sec. metastatic resection after downsizing in 9 patients (17%) and a R0 resection offering curative option in 6 patients (11%) out of a total collective of 53 treated patients (Wein et al, Ann Oncol 2001). The objective of this phase II trial is to verify whether a combination therapy based on ox may improve the curative option in terms of a sec. metastatic resection in a patient cohort with identical inclusion - and exclusion criteria. Methods: Prospective evaluation of 50 patients.; palliative chemotherapy: ox (oxaliplatin, 85 mg/m2 i.v. as a 2h-infusion (inf.); d 1, 15, 29 qd 57) followed by 5-FU (2000 mg/m2 i.v. as a 24h- inf.; d 1, 8, 15, 22, 29, 36 qd 57) together with s-FA (Oncofolic, 500 mg/m2 i.v. as a 24h-inf.; d 1, 8, 15, 22, 29, 36 qd 57) via a miniature pump system. Results: Last date of evaluation: Sep/30/2008; median age: 63 years; chemoth. appl.: total number: 935; higher grade toxicity (grade 3+4): diarrhea 20,0 %, nausea 4,0 %; vomitus 6,0 %; hand-foot-syndrome 2,0 %; fever/infection 2,0 %; response: CR: 2,0 %; PR: 52,0 %; SD: 32,0 %; PD: 12,0 %; not evaluable: 2,0 %; tumor control (CR, PR, SD): 86,0 %; sec. metastatic resection: R0: 28,0 %; R1: 2,0 %; R2 8,0 %; TTP (n = 50): 9,8 months. Conclusion: Combination chemotherapy with weekly 5-FU and s-FA (AIO) plus bi-weekly ox on an outpatient basis is an effective palliative treatment schedule offering a high rate of curative metastatic resection with solely low grade toxicity and no higher grade neurotoxic side effects. Final results in terms of median survival remain to be seen whereas they are certainly influenced by the second line therapy. No significant financial relationships to disclose.
RIPK1 gene polymorphism as a prognostic marker for survival in patients with colorectal cancer
Authors: Chae Y. , Kim J. , Sohn S. , Kim S. , Lee S. , Moon J. , Jeon S. , Cho Y. , Choi G. , Jun S. 
Published: August 2020

e15078 Background: Since apoptosis plays a key role in cancer progression, we hypothesized that single nucleotide polymorphisms (SNPs) of apoptosis-related gene can affect survival after curative resection in patients with colorectal cancer. Patients and Methods: Three hundred and ninety seven patients with colorectal cancer who underwent surgery with curative intent were enrolled in the present study. The genomic DNA was extracted from fresh colorectal mucosal tissue, and the 19 SNPs of 15 apoptosis-related genes (CASP3, CASP6–10, FAS, FAS ligand [FASLG], TNSFR1A, TNSFR10B, RIPK1, BCL2, BCL2 ligand [BCL2L], TP53, and PTGS2) were determined using a PCR-RFLP assay. Results: The median age of the patients was 63 years (range, 21–85), and 218 (54.9%) patients had colon cancer and 179 (45.1%) patients rectal cancer. Pathologic stages after surgery were as follows: stage 0/I (n=86, 21.7%), stage II (n=146, 36.8%), stage III (n=145, 36.5%), and stage IV (n=20, 5.0%). Multivariate survival analysis including pathologic stage, differentiation, age, and CEA level showed that relapse-free survival for the patients with the GA+AA genotype of RIPK1 (Receptor interacting serine/threonine kinase 1) +83G>A (rs2272990) was worse than for the patients with the GG genotype (hazard ratio [HR]=1.66, 95% confidence interval [CI]=1.03–2.68, p=0.038). However, no associations were observed between the polymorphisms and overall survival (OS) in a multivariate analysis. Conclusions: RIPK1 gene polymorphism can be considered as a possible prognostic marker for survival after curative resection in patient with colorectal cancer. No significant financial relationships to disclose.
A predictive test for therapeutic treatment outcomes of advanced gastrointestinal cancer patients (AGC)
Authors: Pandya N. B. , Tkaczuk K. R. , Tait N. , Ioffe O. , Tan M. , Van Echo D. A. , Sutula M. J. , Lesko S. A. , Deamond S. F. , Ts’o P. O. 
Published: August 2020

e15079 Background: There are currently limited options for selecting an optimal treatment regimen for AGC patients. The Drug Response Indicator Test (DRIT) is a platform technology that provides a detailed profile of a patient's tumor response to commonly used chemotherapeutic drugs, as a basis for individualized treatment. Establishment of DRIT will allow physicians to choose effective drug treatments to improve the efficacy of cancer therapies on an individual basis. Methods: DRIT analysis is based on fluorescent dye-labeled monoclonal antibody staining followed by computer-assisted microscopy to measure expression levels in tumor sections. The interpretation of the Drug Response Indicator (DRI) expression levels result in classification of tumors as sensitive or resistant to treatment with a mechanistically related drug. Clinical outcomes are then analyzed with respect to the DRI data. This study utilized the following drug/DRI combinations: capecitabine, 5-flurouracil/thymidylate synthase; docetaxel, paclitaxel, abraxane/β-tubulin isoform III; gemcitabine/ribonucleotide reductase; platinum salts/ERCC-1; Irinotecan/Topoisomerase I. Results: DRIT retrospective studies were performed on a cohort of 33 consented patients (pts) receiving 55 treatments for AGC at UMGCC. This cohort included pts treated for rectal/colon, gastric, esophageal & pancreatic cancers. DRIT sensitivity was 0.96, positive predictive value 0.84, negative predictive value 0.67 and overall predictive accuracy 83 %. DRI expression level cut-off points indicating sensitivity or resistance to a specific treatment were derived from previous retrospective breast cancer studies using similar drug complements (abstract 6075 San Antonio Breast Conference 2008). Conclusions: This study indicates that DRIT can provide accurate prediction of treatment outcomes for individual AGC patients. DRI expression level cut-off points indicating sensitivity or resistance to a specific treatment may be applied to both breast cancer & AGC. DRIT will allow for tailoring of chemotherapy based on the specific biomarker expression within each patient's tumor tissue. [Table: see text]
Association of integrin beta-3 polymorphism and chronic oxaliplatin-induced peripheral neuropathy: Preliminary results
Authors: Antonacopoulou A. , Argyriou A. , Kottorou A. E. , Scopa C. D. , Kalofonos H. P. 
Published: August 2020

e15082 Background: Peripheral neuropathy (PN) is widely recognised among the major non-haematological dose- limiting toxicities of oxaliplatin (OXL) which is used to treat advanced or metastatic colorectal cancer (CRC). OXL induces two clinically distinct forms of PN. The acute transient syndrome and the chronic OXL-induced peripheral neuropathy (OXLIPN). The integrin beta-3 (ITGB3) polymorphism at residue 33 (L33P) has been previously associated with altered adhesion ability and ERK2 activation. Thus it may affect neuronal survival. The aim of the current study was to investigate the role of the ITGB3 polymorphism at residue 33 in the development of chronic OXLIPN. Methods: Thirty four patients with advanced CRC were genotyped. All patients, 22 males and 12 females had received adjuvant chemotherapy consisting of 12 courses of the formal FOLFOX-4 regimen. Following the discontinuation of treatment, 20 of the patients (58.8 %), developed OXLIPN, whereas the remaining 14 (41.2%) patients remained unaffected with normal peripheral nerve function. The grading of the OXLIPN severity was defined by Total Neuropathy scores, corresponding to the WHO grading scales 1–3 for chemotherapy-induced PN. Genotyping was performed using allele specific primers and sybr green in real time polymerase chain reactions. Statistics were performed using the SPSS for Windows (release 16.0). Results: Patients with normal peripheral nerve function OXLIPN were 14.3% homozygous for C, 28.6% heterozygous and 57.1% homozygous for T. The corresponding percentages for patients who developed OXLIPN did not differ significantly and were 5%, 25% and 70%, respectively. The majority of patients with mild OXLIPN were heterozygotes (50%, with 16.7% CC and 33.3% TT), whereas the majority of patients with moderate OXLIPN were homozygous for TT (85.7% with the remaining 14.3% being CT). Notably, the TT genotype was associated with increased OXLIPN compared to the genotypes containing the C allele (p= 0.046). Conclusions: The ITGB3 polymorphism at residue 33 appears to be unrelated to the development of OXLIPN but related to the grade of OXLIPN.Further study on this important clinical issue is warranted. No significant financial relationships to disclose.
Correlation between K-ras mutations status and benefit from cetuximab treatment in advanced colorectal cancer
Authors: Xie L. , Lai R. , Wu X. , Zhang S. , Tang X. , Chen T. 
Published: August 2020

e15084 Background: Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We follow -up study the efficacy and toxicity of cetuximab with chemotherapy in the treatment of advanced colorectal cancer from Chinese in East China. Methods: We analyzed tumor samples from 120 patients with advanced colorectal cancer by direct sequencing, to observe the mutations status in exon 2,3 of K-ras gene. And 30 patients were followed up according the RECIST standard for their treatment outcome of cetuximab plus chemotherapy at 2 -12 months. Results: K-ras mutations were identified in 48 of 120(40%) patients with colorectal cancer in exon2, which including 8 mutation types; 38/48(79.2%) mutations in 12 codon(G12D 43.7%,G12V 25%,G12C 10.4%,G12R 6%,G12S 4%,G12A 2%) and 10/48(18.7%) in 13 codon(G13D 18.7%,G13C 2%). None mutation was found in 61codon of exon3. we observed the clinical efficacy of 30 patients treated by cetuximab plus chemotherapy, of 21 patients with wild-type K-ras tumors as compared with 9 patients with mutated K-ras significantly improved the response rate (5/21 21.8% vs 1/9 11.1%,P<0.01)and the disease control rate (19/21 90.4% vs,2/9 22.2%,P<0.01). There were a few patients with mutated K-ras tumors benefit from cetuximab, in which the fluorescence intensity of mutation cells of all detected tumor tissue approach to 1:3 status by sequencing analysis. The major toxicities of treatment were acne-like rash, which were found in 14/21(66.6%)of patients with wild-type K- ras, and 5/9(55.5%)of patients with mutated K-ras . Conclusions: The East-China patients share the same (40%) mutation frequency and type of k-ras gene with other races . Patients with wild type K-ras mutation have significantly higher Response rate and disease control rate on cetuximab plus chemotherapy treatment .Our results once again show that somatic mutations status of k-ras is a major determinant of cetuximab response in advanced colorectal cancer. There was no statistical correlation between acne-like rash of the major toxicities and mutations status of k-ras. There were a few patients bearing mutated k-ras did benefit from cetuximab, that would need to be validation between Chinese or Ethnicity association phenotype by a large numbers of samples. No significant financial relationships to disclose.
Nfy-c expression in colorectal cancer
Authors: Kottorou A. E. , Antonacopoulou A. G. , Skarlas L. , Grivas P. D. , Scopa C. D. , Makatsoris T. , Kalofonos H. P. 
Published: August 2020

e15086 Background: Nuclear factor Y- C (NFY-C) gene encodes one of the three subunits of nuclear factor Y, a highly conserved transcription factor which binds to the promoters of a variety of genes, which are implicated in cell cycle progression, drug metabolism and antigen presentation. The purpose of the current study was to investigate the role of NFY-C in colorectal cancer by evaluating its mRNA expression in both malignant and normal colonic tissue from patients with colorectal carcinomas with and without disease relapse. Methods: Publicly available expression microarray data were analyzed to reveal elevated levels of NFY-C in patients with colorectal carcinoma who relapsed compared to patients who remained disease free. The mRNA levels of NFY-C were evaluated by quantitative RT-PCR in 81 neoplastic colorectal tissue specimens and 23 normal tissue specimens from patients with colorectal cancer who had undergone curative resections at the University Hospital of Patras, Greece, between 1995 and 2005. The mRNA levels were analysed in relation to clinicopathological parameters. Results: No significant difference was found in the expression levels of NFY-C between normal and malignant tissues. The expression levels of NFY-C were not related to age, gender, grade, stage or primary site of the disease. However, a statistically significant difference (p=0.02) was observed in NFY-C levels between patients with and without disease recurrence. More specifically, patients with low NFY-C levels relapsed more often than patients who overexpressed NFY-C. Nevertheless, the expression was not related to time to disease progression. Finally, patients with higher NFY-C expression levels seem to have improved survival, compared to patients with low NFY-C expression levels although the difference was not statistically significant. Conclusions: Expression levels of NFY-C seem to be associated with disease recurrence. The role of NFY-C in colorectal cancer warrants further investigation. No significant financial relationships to disclose.
Treatment of cetuximab-associated cutaneous side effects using topical aplication oh vitamin K1 cream
Authors: Ocvirk J. , Rebersek M. 
Published: August 2020

e15087 Background: The EGFR-targeting monoclonal antibody cetuximab has been licensed by the EMEA in combination with chemotherapy for the treatment of 1st line metastatic colorectal cancer (mCRC) patients (pts) whose tumors have KRAS wild type status. The major side effects of cetuximab are cutaneous reactions (approx. 80% of pts.) predominantly consisting of an acne- like rash 60–100%, but also including pruritus, dry skin (35%), desquamation, hypertrichosis and nail disorders (10–40%). If not properly managed, they have the potential to cause dose reductions and delays, which may in turn impact on treatment efficacy. The aim of our study was to determine the efficacy of topical vitamin K1 cream in pts with cutaneus side effects caused by cetuximab therapy. Methods: Between January 2007 and August 2008, 79 pts with mCRC were treated with weekly cetuximab in combination with chemotherapy. Topical use of a cream containing urea and 0.1% vitamin K1 was applied when an acne-like rash (NCI CTCAE version 3) appeared . Pts were monitored weekly for at least 12 weeks. Results: Sixty nine patients developed an acne-like rash after a median of 1.2 weeks after first cetuximab administration (range 1- 4), 20 pts grade 3, 38 grade 2 and 11 grade 1. Twice-daily application of vitamin K1 cream resulted in a gradual decrease in cutaneous toxicity. Median time to improvement (all toxicity grades) was 1.2 weeks and 2.3 weeks to a down-staging of the rash by at least 1 grade. Dose reduction of cetuximab was necessary for only 5 of the 20 pts with grade 3 toxicity. No dose reductions or treatment delays were needed for any patient with grade 1 or 2 cutaneous toxicity. Topical clindamycin was used concomitantly in 12/20 and 2/38 pts with grade 3 and grade 2 reactions respectively. No toxicity was associated with the topical use of vitamin K1cream. Conclusions: This study demonstrated the efficacy of topically applied vitamin K1 containing cream in the management of cetuximab-induced acne-like skin rash. No significant financial relationships to disclose.