bluuebunny/crossref_metadata_2025_split huggingface dataset:
Encouraging results from a phase I study of capecitabine (X), irinotecan (I) and oxaliplatin (O) as first-line therapy in patients (pts) with metastatic colorectal cancer (MCRC)
Authors: Maroun J. , Jonker D. , Cripps C. , Goel R. , Lister D. , Chiritescu G. 
Published: March 2020

4086 Background: First-line treatment with I, O and infusional 5-FU/Leucovorin (LV) triplets is associated with high response rates and long survival in MCRC. The oral fluoropyrimidine X is better tolerated and shows improved response rates vs. 5- FU/LV in MCRC. This dose-escalation study aims to establish dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of I, O and X and to evaluate efficacy and safety in first-line. Methods: Starting doses were: I (180mg/m2 i.v. d1), O (85mg/m2 i.v. d1), × (850mg/m2 bid orally d2–15). Dose escalations are based on toxicity observed at previous dose level (DL), until DLT, MTD and RPIID are reached. Results: We have enrolled 27 pts (21 men, 6 women), median age 59 years (range 25–74), at 6 DLs. ECOG PS was 0 or 1 in 25 pts, and 2 in 2 pts. Pts received a median of 10 cycles (range 1–23). All pts are evaluable for toxicity (24 for efficacy). Most common grade 3/4 hematological adverse events (AEs) during dose escalation: granulocytopenia (41%), anemia (7%), and thrombocytopenia (15%). Most common grade 3 non-hematological AEs: late-onset diarrhea (11%), fever (14%), and fatigue (4%). DLTs at each dose level: DL1 (1 febrile neutropenia with bowel perforation); DL2 (1 grade 3 diarrhea); DL3 (1 febrile neutropenia with grade 2 edema); DL4 (1 severe febrile neutropenia in cycles 2&3, pt deceased due to sepsis); no DLTs were reported at DL5 & 6. MTD has not yet been reached. Overall response rate is 79% (95% CI, 62–97%), including 2 CRs and 17 PRs (3 still unconfirmed). Disease control rate is 92%. Two pts had subsequent curative liver resection and 4 pts are under consideration for curative procedures. Median progression-free survival is 15 months (95% CI, 8–22). Conclusions: XIO is well tolerated and highly effective as first-line treatment for MCRC. Severe neutropenia was significant but of short duration and manageable; it is likely to be the main DLT. MTD has not yet been identified but is expected shortly. A phase II study to confirm the efficacy and safety of XIO, possibly in combination with targeted agents, will follow. Supported by Roche, Sanofi-Aventis, and Pfizer Canada. No significant financial relationships to disclose.
CETUFTIRI, a new combination of UFT with leucovorin (LV), irinotecan, and cetuximab as first-line treatment for patients (pts) with unresectable metastatic colorectal cancer (mCRC): Preliminary results from a multicenter phase II trial
Authors: Bennouna J. , Faroux R. , François E. , Ligeza C. , El Hannani C. , Perrier H. , Jacob J. , Desseigne F. , Perrocheau G. , Douillard J. Y. 
Published: March 2020

4087 Background: A phase II study (ASCO 2004) established that the combination of UFT (tegafur-uracil) with LV and irinotecan (TEGAFIRI) could be safely administered to pts with unresectable mCRC, with an objective response rate (ORR) of 34% and a median time to progression (TTP) of 5.7 months. We initiated CETUFTIRI, a phase II study, to evaluate the efficacy and tolerability of cetuximab added to TEGAFIRI in chemonaïve pts with unresectable mCRC. Methods: Patients in this single-stage study were aged =18 years, with histologically or cytologically confirmed, bidimensionally measurable mCRC, ECOG performance status 0 or 1, and adequate bone marrow, renal, and hepatic function. EGFR expression was not an inclusion criterion. Treatment consisted of UFT 250 mg/m2/day d1–14, LV 90 mg/day d1–14, and irinotecan 250 mg/m2 d1 every 3 weeks, plus cetuximab 400 mg/m2 week 1 then 250 mg/m2 weekly thereafter. The primary endpoint was ORR and the planned sample size was 61 pts. The study is now closed to accrual. Results: To date, 48 patients are evaluable for safety and 31 are evaluable for efficacy. Patient characteristics (n=48): median age 65 years (range 45–84 years); ECOG PS 0/1: 73/27%; male 65%; tumor sites: colon 69%; rectum 17%; junction 14%; liver metastasis 83%; lung metastasis 46%; other 27%. Adverse events per patient (n=48) after a total of 230 cycles were: grade G3 mucositis 10%; G3/4 neutropenia 10%; G3 nausea/vomiting 8%; G3 asthenia 6%; febrile neutropenia 6%; G3 hypokalemia 6%; G3/4 anemia 4%; G3 diarrhea 2%; acne-like rash G1/2 50% (G3 4%); infusion- related reaction to cetuximab 6%. Two of 31 evaluable pts had a complete response and 11 had a partial response, for an ORR of 42%; 5 pts had stable disease (16%) and 11 pts had progressive disease (35.5%). An independent radiologist review is planned for all 61 pts included up to December 2006. Conclusions: The CETUFTIRI combination seems to have an acceptable toxicity profile with an attractive objective response rate in the first-line treatment of pts with mCRC. No significant financial relationships to disclose.
Results of a phase II trial of cetuximab + XELIRI as first-line therapy of patients with advanced and/or metastatic colorectal cancer
Authors: Cartwright T. H. , Kuefler P. , Cohn A. , Hyman W. , Yoffe M. , Boehm K. A. , Ilegbodu D. , Asmar L. 
Published: March 2020

4094 Background: We have previously shown that capecitabine/irinotecan (XELIRI) is effective and well-tolerated in metastatic colorectal cancer (mCRC). Cetuximab, a monoclonal IgG1 antibody that binds to the extracellular domain of EGFR, is active in mCRC alone or in combination with chemotherapy. This study was designed to evaluate if cetuximab (Erbitux®) added to XELIRI improves outcome in first-line treatment of mCRC. Methods: Subjects had histologically confirmed colorectal adenocarcinoma with T4 lesions that were unresectable after preoperative chemoradiation therapy and/or metastases. The study regimen was capecitabine 1700 mg/m2 (850 mg/m2 PO BID Days 1–14), irinotecan 200 mg/m2 IV Day 1 every 3 weeks, and weekly cetuximab (initial dose 400 mg/m2 IV over 120 minutes, subsequent doses 250 mg/m2 over 30 minutes). Results: Between February and October 2005, 70 subjects enrolled. Baseline characteristics: 43 males (61%), median age 61.5 years, and ECOG PS 0/1= 66%/34%; 94% of subjects had adenocarcinoma. Prior therapy; surgery (91%), chemotherapy (20%), or radiotherapy (7%). Responses (pts >2 cycles) were; CR (4%), PR (36%), SD (40%) and PD (20%); 15 patients failed treatment; (n=4 allergic reaction, n=2 MD request, n=2 withdrew consent, n=2 Grade 4 neutropenia, and n=5 other AEs). The overall response rate was 40% and the disease control rate was 80%. Median duration of response was 8.8 months (range, 2.6–15.1) and median time to response was 2.0 months (range, 1.2–8.3). 64% of patients remain alive; of the 25 deaths, 84% were due to PD. No death was drug related. The most frequent Grade 3 and 4 treatment-related adverse events (AEs) included: diarrhea (25%), neutropenia (18%), nausea/vomiting (12%), rash and dehydration (9%, each), HFS and fatigue (7%), and allergic reaction (6%). 54% of patients required dose reductions. To date, 64 patients (91%) have gone off study, primarily due to PD (39%) or AE (33%); 3 patients remain on treatment. Conclusions: The combination of cetuximab and XELIRI is feasible and tolerable in first line mCRC. Toxicities are expected and manageable with dose reductions/delay. Funded in part by Bristol-Myers Squibb, Plainsboro, NJ. No significant financial relationships to disclose.
Predictors of colon cancer screening among low-income urban minority residents: The Cancer Risk Assessment in Baltimore (CRAB) Study
Authors: Mentor-Marcel R. A. , Visvanathan K. , Garza M. A. , Xie Y. , McCaffrey L. , Ford J. G. 
Published: March 2020

4101 Background: Colorectal cancer mortality can be reduced through early detection, using recommended screening tests (fecal occult blood test (FOBT), sigmoidoscopy, or colonoscopy). However, screening is underutilized, especially among low-income and racial/ethnic minority groups. Few studies have examined determinants of screening in these groups. Methods: We analyzed data on predictors of colon cancer screening from a cross-sectional study of Baltimore City Residents (N = 534). Participants responded to a questionnaire administered by an interviewer, on screening practices, behavioral, social and demographic factors, including income level. Eligible respondents for this analysis were age = 50, aware of colorectal screening tests, but not diagnosed with colon polyps or cancer. Multivariate techniques were used to examine predictors of having undergone any recommended colon cancer screening test. Results: The eligible population for this analysis (N=202) was 49.0 % male and 51.0 % female. The median income fell within the $12,000-$24,999 bracket. The proportion of participants that had received colon cancer screening was 34.5 % among those in the highest income bracket (i.e. =$25,000) compared to 30.0 % in the lowest income bracket (i.e. =$11,999). This difference was statistically significant after adjusting for other sociodemographic factors (odds ratio (OR)=3.12, p=0.023). Multivariate analysis indicated that screening was associated with having one (OR: 3.56, p=0.016) or more than one (OR: 7.31, p=0.006) primary health care provider. Having health care coverage, a doctor who recommended exercise, and having at least some college education, were also associated with screening. Conclusions: Negative predictors of colorectal cancer screening include: extremely low income levels (= $11,999), lack of health care coverage, primary care providers, and college education level. Provider recommendations for healthy behaviors (e.g. exercise) are associated with patient adherence to recommended cancer screenings. The design of interventions to promote use of screening tests by low-income populations should be informed by the substantial heterogeneity in patient and provider characteristics within these populations. No significant financial relationships to disclose.
Randomized multicenter phase III trial of oxaliplatin plus raltitrexed compared to oxaliplatin plus fluorouracil and leucovorin treatment in recurrent and metastatic colorectal cancer
Authors: Wang J. , Li J. , Qin S. , Liu T. , Ye Z. , Zheng L. , Tao M. , Zhuang Z. , Zhang Q. , Xu N. , Zhang Y. 
Published: March 2020

4102 Purpose: To compare oxaliplatin (L-OHP) plus raltitrexed (RTX) with L-OHP plus fluorouracil and leucovorin (LV/5FU) for patients (pts) with recurrent and metastatic colorectal cancer(CRC). Methods: Eligible pts had to have histologically proven recurrent or metastatic CRC,not having previously received oxaliplatin as palliative chemotherapy,ECOG PS = 2,age:18∼70,and adequate hematological,renal and hepatic function.After written informed consent,pts were randomized to L-OHP:130 mg/m2 d1 + RTX: 3 mg/m2 d1 (Arm A) or + LV: 200 mg/m2 + 5FU:375 mg/m2 d1–5 (Arm B). Results: Between Jan 2005 and July 2006, 216 pts were enrolled at 15 centers in China.112 pts (mean age: 55.0 (19∼70), M/F: 57/46, PS 0/1/2: 46/53/13) were randomly assigned to A and 102 (mean age: 54.2(22∼70), M/F: 54/46, PS 0/1/2: 44/59/9) to B. 203 pts were eligible for response evaluation (A:103, B:100).The median number of cycles was 4 (1∼6) in A and 3 (1∼6) in B (P=0.1431).The RR was 29.1% (CR:2, PR:28, SD:50 , PD:23) in A and 17.0% (CR:2, PR:15, SD:46 , PD:37) in B (P=0.0437).The disease-control rate was 77.7% in A and 63.0% in B (P=0.0237). After a median follow-up of 10 months (4–16.5),92 pts had had progression of disease (40 in A and 52 in B); 73 deaths had occurred (35 in A and 38 in B), median time to progression was not reached. Following-up is ongoing.The median QoL scores for the two arms were comparable. 214 were included in the safety analyses (A:112, B:102). There was a higher incidence of neutropenia (48.2% verse 29.4%, P=0.005) and transaminase increase (49.1% verse 35.3%, P=0.041) among A. Grade 3 or 4 neutropenia was much common in pts in A than those in B (20.5% verse 4.9% , P=0.001), but was complicated by fever in only 3.6% of cases (4 pts) in A and in 2.9% of cases (3 pts) in B. No pts were dead or infectious due to neutropenia. There were similar rates of grade 3 or 4 transaminase elevation in the two groups. Vomitting and anorexia were much commoner with B. Conclusions: The L-OHP+RTX seems beneficial in recurrent and metastatic CRC, demonstrating better response rate and higher disease control rate with acceptable tolerability, maintenance of QoL and convenient administration schedule. No significant financial relationships to disclose.
Application of the RTOG recursive partitioning analysis classification to brain metastases from colorectal cancer
Authors: Yasui H. , Yoshino T. , Boku N. , Onozawa Y. , Hironaka S. , Fukutomi A. , Yamazaki K. , Machida N. , Tochikubo J. , Mitsuya K. 
Published: March 2020

4104 Background: Colorectal cancer infrequently causes brain metastases (BMs). Recently, the incidence of BMs from colorectal cancer (CRC) has been reported to be increasing as 3 % of all metastatic CRCs, especially in patients (pts) with lung metastases (LMs). The RTOG previously developed three prognostic classes for BMs using a recursive partitioning analysis (RPA) classification, including Karnofsky performance status, controlled primary tumor, extracranial metastases, and an age. However, the relevance of this classification for CRC remains unclear, because only a few CRC pts were included in the RTOG database. The present studies retrospectively evaluate the usefulness of RPA classification for BMs from CRC. Methods: The subjects were consecutive 290 metastatic CRCs without symptomatic BMs who treated with any chemotherapy initiated in our institution between 2002 and 2005. The treatment of BMs, including whole brain radiation therapy (WBRT), surgery, and stereotactic radiosurgery (SRS), were indicated for pts whose life expectancy was considered to exceed 3 months (M). Results: BMs were detected in 20 pts out of 133 (15%) with LMs at base line, with a median follow-up time of 17.7 M. In the remaining 157 pts, BMs were found in 3 pts out of 41(7%) who had developed LMs during follow-up and 2 pts out of 116 (2%) without LMs. In total, overall incidence of BMs was 9% (25/ 290). Median duration from the diagnosis of LMs to BMs was 12 M (range: 4.4–33.6). According to RPA, the 25 pts with BMs were classified into Class I 0 (0%), Class II 12 (48%) and Class III 13 (52%). Treatments for BMs were performed to all pts of Class II, and to 6 pts (46%) of Class III. Median overall survivals from detecting BMs were Class II 9.7 M and Class III 3.0 M (logrank test; p=0.02). In the 18 pts treated for BMs, median BMs progression-free survival of Class II and Class III were 3.0 M and 3.1 M. Conclusions: It is suggested that the incidence of BMs from CRC is more common than previously reported. Overall survivals for BMs reproduce the results from RPA classification. No significant financial relationships to disclose.
Epidermal growth factor receptor (EGFR) mRNA expression levels are strongly correlated between primary colorectal cancer and corresponding liver metastases
Authors: Kuramochi H. , Hayashi K. , Uchida K. , Yamamoto M. , Danenberg K. D. , Danenberg P. V. 
Published: March 2020

4106 Background: As it has been well known that epidermal growth factor receptor (EGFR) is strongly related to a tumor proliferation and a metastasis, new EGFR-inhibitory small molecules, such as gefitinib and erlotinib, and EGFR antibodies have been developed recently. It is reported that the high expression levels of EGFR mRNA are associated with high response probability and longer progression-free survival in gefitinib-treated lung cancer patients. Thus, since liver metastases are the main cause of death for most of colorectal cancer (CRC) patients, it is reasonable to expect that measurement of EGFR gene expression levels in liver metastases would provide the best prediction of therapy benefit, but in most cases, only biopsies of the patient’s primary tumor are readily available for analysis. Our aim was to determine how EGFR gene expression levels in primary CRC were related to those in liver metastases. Methods: Thirty-one pairs of primary CRC and corresponding liver metastases were analyzed. (18 males and 13 females: Median age 66 (range 45–85)). Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse-transcription. Quantitation of target gene and internal reference gene was performed using real-time PCR (Taqman PCR). Results: No significant difference was seen between median mRNA expression levels of EGFR in primary cancer and those in corresponding liver metastases (Median value: 1.35 vs 1.24, p=0.99 , Wilcoxon signed rank test), although the median value of EGFR mRNA from normal liver tissue is significantly higher than those from normal colon mucosa (Median value: 5.06 vs 1.39, p<0.0001). When matched tissue sets were compared on an individual basis, there was a significant correlation for EGFR mRNA expression between primary cancer and corresponding liver metastases (rs=0.78, p<0.0001, Spearman rank correlation coefficient). Conclusions: A good prediction of EGFR mRNA levels in liver metastases can be obtained by measuring those of primary CRC. No significant financial relationships to disclose.
Molecular markers associated with response and clinical outcome to cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer (BOND2)
Authors: Azuma M. , Yang D. , Carpanu M. , Hollywood E. , Lue-Yat M. , Zhang W. , Danenberg K. D. , Danenberg P. V. , Saltz L. , Lenz H. 
Published: March 2020

4113 Background: Phase II (BOND2) trial of Cetuximab/Bevacizumab/Irinotecan (CBI) vs Cetuximab/Bevacizumab (CB) has shown that bevacizumab added to the efficacy of cetuximab and cetuximab/irinotecan in irinotecan-refractory bevacizumab-naïve CRC patients. We tested whether expression levels of genes involved in angiogenesis (VEGF, IL-8), the EGFR pathway (EGFR, COX2) and DNA repair (ERCC1) are associated with clinical outcome. Patients and Methods: This randomized phase II trial enrolled 81 patients. Treatment plan as: Arm A received IRI at the same dose and schedule as last received prior to study, plus Cetuximab 400 mg/m2 loading dose, then weekly at 250 mg/m2, plus Bevacizumab 5 mg/kg given every other week. Arm B received the same as arm A, but without IRI. FFPE samples for 35 out of 81 patients (M:W 24:11, median age 56 (29–80) enrolled in the BOND2 study were tested. Patients received either with CBI (n=18, Arm A) or with CB (n=17, Arm B). FFPE tissues were dissected using laser-captured microdissection and analyzed EGFR, ERCC1, VEGFA, VEGFR2, COX2, Cyclin D1, IL-8, and NRP1 mRNA expression using a quantitative real-time RT-PCR. Gene expression values are expressed as ratios between the target gene and internal reference gene. Results: All eight genes and treatment arm were considered in the CART analysis. The classification tree for response, progression-free survival, and overall survival are evaluated. The expression levels of VEGFR2 and NRP1 classified patients in 3 response groups with response rate range from 61% to 0%. Patients who were classified as responders (Group I; VEGFR2=0.65 and NRP1<2.285) were at a lower risk for progression, compared with patients who were classified as non- responders (Group II; VEGFR2=0.65 and NRP1=2.285 and Group III; VEGFR2<0.65). The expression levels of NRP1 and ERCC1, and EGFR and VEGFR2 were chosen to classify patients into 3 groups with distinct risk of progression-free survival and overall survival, respectively. Conclusion: These data suggest that gene expression levels may be molecular markers of response for patients with mCRC treated with CBI or CB. Prospective studies are needed to validate these preliminary findings. No significant financial relationships to disclose.
Relationship of insulin-like growth factor-1 receptor and epidermal growth factor receptor expression to clinical outcomes in patients with colorectal cancer
Authors: Takahari D. , Yamada Y. , Okita N. , Hirashima Y. , Matsubara J. , Takashima A. , Kato K. , Hamaguchi T. , Shirao K. , Shimada Y. , Shimoda T. 
Published: March 2020

4117 Background: Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), and HER2 have been reported to regulate tumor growth by interfering with apoptosis, cell proliferation, angiogenesis, and metastasis. However, the clinical significance of these molecules in colorectal cancer (CRC) remains undetermined. To gain further insight, we evaluated the prognostic implications of these biomarkers in patients with CRC treated with fluoropyrimidines or irinotecan. Methods: The study group comprised 91 patients who underwent surgery at National Cancer Center Hospital and subsequently received fluoropyrimidines as 1st-line chemotherapy for recurrent or residual tumors. The expressions of IGF-1R, EGFR, and HER2 in surgically removed specimens of primary lesions were analyzed immunohistochemically to determine the prognostic significance of these biomarkers. Results: IGF-1R expression (defined as >10% membranous staining) was found in 81 tumors (89%), EGFR in 77 (85%), and HER2 in 3 (3%). IGF-1R expression significantly correlated with EGFR expression (P=0.038). Overexpression (defined as >50% membranous staining) of IGF-1R was found in 48 tumors (53%), EGFR in 57 (63%), and HER2 in 2 (2%). Overexpression of IGF-1R significantly correlated with shorter survival from the start of 1st-line chemotherapy (P=0.032). Overexpression of EGFR was a significant predictive factor for a clinical response to fluoropyrimidines (P=0.037) and tended to correlate with TTP in patients given irinotecan as 2nd-line therapy (P=0.087). A multivariate analysis of potential prognostic factors showed that IGF-1R expression and worse performance status were independent predictors of poor outcomes ( Table ). Conclusions: IGF-1R and EGFR were highly positive in patients with CRC. Overexpression of IGF-1R predicts a poor outcome, and overexpression of EGFR predicts a good clinical response to fluoropyrimidines. [Table: see text] No significant financial relationships to disclose.