bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capecitabine plus irinotecan versus 5-FU/FA/irinotecan ± celecoxib in first line treatment of metastatic colorectal cancer (CRC). Long-term results of the prospective multicenter EORTC phase III study 40015
Authors: De Grève J. , Koehne C. , Hartmann J. , Lang I. , Vergauwe P. , Becker K. , Braumann D. , Debois M. , Bethe U. , Van Cutsem E. 
Published: March 2020

3577 Background: Oral fluoropyrimidines in combination with irinotecan may be an alternative to infusional 5-FU/FA+irinotecan. Cox-2 inhibitors may enhance the antineoplastic activity of chemotherapy (CT). Methods: Patients with ECOG PS<2, age>18 and measurable disease were randomised in a 2×2 factorial design to FOLFIRI (Douillard’s regimen) or capecitabine 2×1g/m2 d1–14 plus irinotecan 250mg/m2 d1, qd22 (CAPIRI), and to daily celecoxib 2x400mg (C) or placebo (P). 692 patients were planned to compare PFS as primary endpoint. The trial was suspended after 85 pts (44 CAPIRI and 41 FOLFIRI) due to the occurrence of 8 fatal events unrelated to disease progression (Köhne, ASCO 2005, A3525). Results: Baseline characteristics were well balanced. Three pts did not start treatment. Of the pts who started CT, 53% (23/43) in the CAPIRI and 33% (13/39) in the FOLFIRI arms required a dose reduction. Grade ≥3 diarrhoea occurred in 37% (16/43) and 13 % (4/39) on CAPIRI and FOLFIRI, respectively. Median number of CT cycles: 3 (CAPIRI) and 5 (FOLFIRI). Median dose intensity for irinotecan: 83% (CAPIRI) and 85% (FOLFIRI). Response rate (RR): 5/23 (22%) in CAPIRI+C, 10/21 (48%) in CAPIRI+P, 6/19 (32%) in FOLFIRI+C and 10/22 (45%) in FOLFIRI+C. RR for CAPIRI vs FOLFIRI: 15/44 (34%) versus 16/41 (39%), RR for Celecoxib vs Placebo: 11/42 (26%) vs. 20/43 (46 %). Median PFS: 5.9 months (95% CI: 4.4–8.9) with CAPIRI vs 9.6 months (95% CI: 6.9–11.8) with FOLFIRI (HR=1.31, 95%CI: 0.8–2.1), and 6.9 months (95% CI: 5.5–10.4) with C vs 7.8 months (95% CI: 6.0–12.0) with P (HR=1.1, 95%CI: 0.7–1.8). Median OS: 14.8 months (95% CI: 10.7–18.3) with CAPIRI vs 19.9 months (95% CI: 18.9-n.a.) with FOLFIRI (HR=3.2, 95%CI: 1.4–7.3), and 18.3 months (95% CI: 10.2-n.a.) with C versus 19.9 months (95% CI: 16.7-n.a.) with P (HR=1.25, 95%CI: 0.6–2.6). Conclusions: The data suggest that celecoxib might reduce response to CT and this warrants further preclinical investigation. The stratified analysis failed to demonstrate the non-inferiority of CAPIRI as compared to FOLFIRI. Small sample size and confounding safety issues prevent us from drawing definitive conclusions. Results of larger studies would be needed. No significant financial relationships to disclose.
Continuous versus intermittent chemotherapy in metastatic colorectal cancer
Authors: Alexopoulos C. G. , Kotsori A. A. 
Published: March 2020

3582 Background: The current policy concerning the duration of chemotherapy in metastatic colorectal cancer (MCC) varies considerably (Clin Oncol 1997;9:248) while no benefit of continuous versus intermittent 5-FU was found in a published randomized study (Lancet 2003;361:457). Serious cumulative toxicity is not usually a problem with long-term 5-FU/FA, but this is not the case with contemporary triple regimens (FOLFIRI, FOLFOX). We, therefore, performed a randomized study of continuous versus intermittent FOLFIRI as first line chemotherapy in MCC. Methods: Patients with MCC and ECOG 0–2 were given 6 biweekly courses of FOLFIRI (Irinotecan 180mg/m2 + De Gramont). Patients with response or stable disease were randomized to continue with another 6 FOLFIRI (group A) or discontinue until relapse when 6 FOLFIRI were readministered (group B). Time to progression (TTP) was calculated from study entrance until 1st progression for group A, and 2nd progression for group B, and overall survival (OS) from study entrance until death. Results: Fifty eight (M=38, F=20) patients entered into the study. Two (3.4%) withdrew before evaluation, 1 (1.7%) died of stroke, 1 (1.7%) was lost to FU and 15 (26%) progressed before or at the completion of 6 FOLFIRI. Thirty nine (67%) patients (M=25, F=14), median age 69 (38–79) responded (21=54%) or had stable disease (18=46%) and were randomized: 19 (49%) to group A and 20 (51%) to group B. Median TTP was 8 months 95% CI: 5.3–10.7) for group A and 9 (95% CI: 7.8–10) for group B (p=NS). 10/19 (52%) in group A received 2nd line chemotherapy vs 7/20 (35%) in group B (p=NS). With a median follow-up of 13 months, 21 patients are alive (12 in group A and 9 in group B). Median OS was 21 months (95% CI: 15 - 26.7) in group A vs 15 (95% CI: 12.6 - 17.3) in group B (p=NS), and 18 months (95% CI: 15.5 - 21) for all 39 patients. Conclusions: In MCC, when response or stability has been achieved after 6 courses ofFOLFIRI there seemstobe little more benefit from continuing chemotherapy than from retreating patients at relapse No significant financial relationships to disclose.
Phase II trial of depsipeptide (NSC-630176) in colorectal cancer patients who have received either one or two prior chemotherapy regimens for metastatic or locally advanced, unresectable disease: A Southwest Oncology Group study
Authors: Whitehead R. P. , McCoy S. , Wollner I. S. , Wong L. , Harker W. G. , Hoff P. M. , Gold P. J. , Billingsley K. G. , Blanke C. D. 
Published: March 2020

3598 The treatment for metastatic colorectal cancer has markedly improved but the disease is still not curable, and additional active agents need to be found. Depsipeptide is a histone deacetylase inhibitor that has shown activity against human solid tumor cell lines and promising results in murine model systems. This phase II trial was undertaken to determine its activity in patients with advanced colorectal cancer. Eligibility requirements included measurable disease, either metastatic or locally advanced and not surgically resectable, Zubrod performance status of 0–1, and adequate renal, hepatic, hematologic and cardiac function. Prior surgery or radiation therapy was allowed and patients were required to have received either one or two prior chemotherapy regimens for advanced disease. A two-stage design was used designed to detect a difference in the null hypothesis of 5% response vs. an alternative 20% response, with 20 eligible patients to be accrued initially followed by an additional 20 patients if one or more confirmed responses were observed. The study closed after the first stage, with 28 patients registered. Three patients are ineligible, two who did not meet requirements for serum magnesium level, and one whose baseline labs were performed more than 14 days prior to registration. One eligible patient never received treatment and is not analyzable for any endpoint. For the 24 eligible and analyzable patients, median age was 58.6 years (range 31–84) with 14 males. Performance status was 0 in 16 patients and 1 in 8. Ten patients received 1 prior chemotherapy regimen and 14 received 2 prior regimens. There were no grade 4 or higher toxicities. The most common grade 2 or 3 toxicities were anorexia, fatigue, nausea, and dehydration. No objective responses were observed. Four patients had stable disease, 15 showed increasing disease, 3 had symptomatic deterioration, and 2 had assessment inadequate. The current Kaplan-Meier estimate of 6 month overall survival is 69% (95% CI 50%-88%) with a median survival of 8.4 months. Depsipeptide does not show significant anti-tumor activity in previously treated patients with advanced colorectal cancer. No significant financial relationships to disclose.
Prognostic value of ERCC1, thymidylate synthase and glutathione S-transferase π for 5-FU/oxaliplatin chemotherapy in advanced colorectal cancer
Authors: Kwon H. , Roh M. S. , Oh S. Y. , Kim S. , Lee J. H. , Kim J. , Park J. I. , Park K. J. , Choi H. J. , Kim H. 
Published: March 2020

3607 Background: The aim of this study was to determine whether expressions of the excision cross-complementing (ERCC1), thymidylate synthase (TS) and glutathione S-transferase π (GSTπ) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy. Methods: The study population consisted of 70 advanced colorectal cancer patients (median age, 53 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at days 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU bolus 400 mg/m2 and 22 hour continuous infusion of 600 mg/m2 at day 1–2. Treatment was repeated in 2 week intervals. The expressions of ERCC1, TS and GSTπ of primary tumors were examined by immunohistochemistry. Results: The positive rates of ERCC1, TS, and GSTπ were 55.7%, 68.6%, and 71.4%, respectively. The patients without TS expression were more likely to respond to chemotherapy (p=0.009). There were no significant differences between response and ERCC1 or GSTπ expression pattern (p=0.768, p=0.589, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (p=0.0474). Patients with ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GSTπ positive had poor OS (p=0.0017, p=0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted on OS (Hazard ratio 1.72, p=0.023). Conclusions: Immunohistochemical studies for ERCC1 and TS may be useful in prediction of the clinical outcome of advanced colorectal cancer patients treated with 5-FU and oxaliplatin. No significant financial relationships to disclose.
Comparative analysis of CT-scan and PET-scan with intraoperative ultrasound (IOUS) in detecting liver metastases
Authors: Patel M. , Saha S. , Sehgal R. , Gallardo L. , Doan K. , Berman B. , Wiese D. , Weiner S. , Arora M. , Singh T. 
Published: March 2020

3632 Background: Open, laparoscopic or percutaneous radiofrequency ablation (RFA) has been used for the surgical treatment of liver metastases (mets). However, it requires accurate preoperative (preop) localization of liver mets. CT scan and PET scan have been widely used for such preop evaluation. However, intraoperative ultrasound (IOUS) remains the gold standard. Very little data is available comparing IOUS with preop CT and/or PET scan. Thus, a retrospective study was done to compare the efficacy of IOUS with preop CT and/or PET scan in detecting the number of liver mets. Methods: A retrospective chart review was done that included all patients (pts) who underwent surgical treatment for liver mets. Data was obtained from medical records, radiology, intraop reports. Results: 53 pts including 57% men and 43% women with a median age of 62years (age range 35–80 years) were included in the study. Imaging data was available for CT, PET and IOUS in 53, 24 and 39 pts respectively. CT, PET, and IOUS detected 2.4, 1.7 and 2.6 lesions/ pt respectively. In 24 patients, both CT and PET scan report was available. Of these, the imaging study detecting the maximum number of lesions was selected for comparison of preop evaluation with IOUS. A comparison between preop imaging (CT/PET scan) vs. IOUS in these 24 pts revealed an average of 2.3 vs. 2.8 lesions/pt respectively ( Table ). When compared with preop imaging (CT/PET scan), IOUS detected additional lesions in 33% pts; fewer lesions in 17% pts and similar number of lesions in 50% pts. Comparison between CT and IOUS in 39 patients revealed 1.9 vs. 2.6 lesions/pt respectively and that between PET and IOUS in 24 patients revealed 1.7 vs. 2.8 lesions/pt respectively. Conclusions: Although CT scan and PET scan remains effective modalities for preop evaluation of liver mets, IOUS is found to be superior for planning accurate surgical treatment. Thus, the efficacy of percutaneous RFA may be limited due to inability to perform IOUS. [Table: see text] No significant financial relationships to disclose.
A randomized clinical study of surgery versus radiotherapy in the treatment of resectable esophageal cancer
Authors: Yu J. , Ren R. , Sun X. , Yin Y. , Fu Z. 
Published: March 2020

4013 Background: To compare the treatment results between radical surgery and late-course accelerated hyperfractionation radiotherapy (LCAHFR) for patients with resectable thoracic segment esophageal cancer. Methods: From June 1998 to September 2002, 269 patients with resectable thoracic esophageal cancer were randomized into two groups. 135 were with surgery and 134 with late-course accelerated hyperfractionated (LCAF) radiotherapy. Chemotherapy only for clinical recurrence and salvage therapy. Results: The 1-, 3- and 5- year overall survival rate were 88.6%, 56.2% and 34.7% in the surgery group and 93.3%, 61.5% and 36.9% in the radiotherapy group. There was no statistical difference between the two groups (P =0.58). Median survival was 28.5 months and 30.5 months respectively. The 1-, 3-and 5-year progression-free survival rate was 73.3%, 39.7% and 20.6% in the surgery group and 75.9%, 43.7% and 23.1% in the radiotherapy group (P =0.65) . There was no difference between the two groups in survival rates including different location and length (P > 0.05). The incidence of failure by hematogenous metastasis and distant lymphatic metastasis in the radiotherapy group (16.6% and 13.3% respectively ) was lower than in the surgery group ( 25.3% and 20.3 % respectively ), there was no significance between them. The incidence of local failure in the radiotherapy and surgery group was 57.3% and 27.8% respectively (P = 0.001) The incidence of death by local reasons was higher than in the surgery group (P = 0.02 ). The incidence of death by distant metastasis was lower than in the surgery group (P = 0.02 ). Conclusion: The treatment results between radical surgery and LCAHFR with conformal radiotherapy for patients with resectable thoracic esophageal cancer were comparable. No significant financial relationships to disclose.
Vascular endothelial growth factor (VEGF) polymorphism is associated with prognosis of patients with gastric cancer
Authors: Chae Y. , Kim J. , Baek J. , Cho E. , Sohn S. , Chung H. , Yu W. , Lee M. , Bae H. 
Published: March 2020

4019 Background: Recent studies demonstrated that the expression of vascular endothelial growth factor (VEGF) family had a prognostic significance in patients with gastric cancer. The present study analyzed VEGF polymorphism and its impact on prognosis in patients with gastric cancer. Methods: Five hundred three consecutive patients with surgically resected gastric adenocarcinoma at a single institution between January 2000 and December 2001 were enrolled into the study. Genomic DNA was extracted from paraffin-embedded tumor tissue and four VEGF (-460T > C, +405C > G, 936C> T, and -1154G > A) genotypes were determined using a PCR-RFLP assay. Results: The median age of patients was 60.0 years (range, 25–83 years), and 337 (67.0%) patients were male. Pathologic stages after resection were as follows: stage 0 (n=6, 1.2%), stage I (n=277, 55.1%), stage II (n=105, 20.9%), stage III (n=74, 14.7%), and stage IV (n=41, 8.2%). The estimated 5-year disease-free survival (DFS) rates according to stage were significantly different (p < 0.0001). Three VEGF polymorphisms (+405C > G, 936C, and -1154G > A > T) were not associated with survival of patients, while -460T > C polymorphism had a prognostic significance. In patients with early stage gastric cancer (stage 0 or 1, n=283), the estimated 5-year DFS and carcinoma-specific survival (CSS) for patients with homozygous genotype (CC or TT) of -460T > C were superior to those for heterozygous genotype (CT) (98.1% versus 90.3%, p=0.0047; 98.1% versus 92.5%, p=0.0284). In Cox multivariate regression, stage and VEGF -460T > C genotype were an independent prognostic factors for both DFS (p=0.007; p=0.010) and CSS (p=0.013; p=0.038). Conclusions: VEGF -460T > C polymorphism was found to be an independent prognostic marker for patients with curatively resected early stage gastric adenocarcinoma. Accordingly, VEGF -460T > C polymorphism can help to identify patients with unfavorable clinical outcome and thereby may be useful to refine therapeutic decisions in early stage gastric cancer. No significant financial relationships to disclose.
Long-term follow-up and compilation of two trials utilizing concurrent paclitaxel/carboplatin/infusional 5-FU/radiation therapy (RT) in patients with localized esophageal cancer involved in the Minnie Pearl Cancer Research Network
Authors: Meluch A. A. , Greco F. A. , Spigel D. R. , Gray J. R. , Thomas M. , Meng C. , Bearden J. D. , Rosenoff S. H. , Hermann R. C. , Hainsworth J. D. 
Published: March 2020

4028 Background: The role of preoperative chemoradiation in patients (pts) with localized esophageal cancer remains unclear. Most preoperative regimens produce 20–30% pathologic complete response (pCR) rates, which predicts improved survival. Our community-based multicenter group performed sequential trials evaluating a novel paclitaxel-containing preoperative chemoradiation regimen, now with median followup > 6 years. Methods: Eligibility: untreated adenocarcinoma or squamous carcinoma of esophagus or GE junction; clinical stage I-III; surgical candidate; ECOG PS 0–2, adequate organ function; informed consent. Pts received paclitaxel 200mg/m2 IV and carboplatin AUC 6.0 IV, days 1, 22; 5FU 225mg/m2, 24 hr continuous infusion, days 1–42; RT 45 Gy in 1.8 Gy/d single daily fractions. Surgical resection was performed 6–10 weeks after completion. Results: 226 pts with the following characterstics were treated: median age 58 years; adenocarcinoma 74%; distal/GE junction 79%; clinical stage II/III 84%. 220 pts (97%) completed preoperative therapy, and 199 pts (88%) had resection. Responses in resected pts: pCR 45% (39% of entire group), PR (microscopic residual) 29%, PR (macroscopic) 15%. After median followup of 75 months, median PFS and overall survival for the entire group were 19 and 26 months, respectively; 3- and 5-year survivals were 40% and 33%, respectively. Median survival was better in pts with pCR vs others (33 vs 21 mo; p=.026). 3-yr survival comparisons of other potential prognostic factors: adeno vs squamous, 43% vs 42%; clinical stage I vs II/III, 63% vs 36% (p=.001); distal location vs others, 38% vs 45% (p=.45). Toxicity data have been previously published; overall 13 pts (6%) had treatment-related death (preop 2, postop 11). Conclusions: This preoperative combined modality regimen was feasible and highly active in a community-based setting. This is one of the largest series of patients treated with an identical preoperative approach and with long-term followup is curative in one-third of pts with localized esophageal cancer. [Table: see text]
Phase II study of cetuximab plus FOLFIRI as first-line treatment in patients with unresectable/metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (FOLCETUX study): Preliminary results
Authors: Pinto C. , Di Fabio F. , Siena S. , Cascinu S. , Rojas Llimpe F. L. , Ceccarelli C. , Mutri V. , Giaquinta S. , Piana E. , Martoni A. A. 
Published: March 2020

4031 Background: Aim of this study was to evaluate efficacy and safety of cetuximab plus FOLFIRI as first-line treatment for advanced gastric or GEJ cancer. Methods: Eligibility criteria: histological diagnosis of stomach or GEJ adenocarcinoma, unresectable/metastatic/recurrent disease, EGFR+ (Dako), measurable disease, no prior chemotherapy for advanced cancer. Pts received cetuximab weekly at 400 mg/m2 iv loading dose, then at 250 mg/m2 iv, CPT11 180 mg/m2 iv d1, LFA 100 mg/m2 iv followed by 5FU 400 mg/m2 iv bolus and 600 mg/m2 iv continuous infusion 22h d1–2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Objective response (OR) activity was assessed by CT and PET at baseline and after 6 weeks, and further by CT± PET every 6 weeks. Results: From November 2004 to December 2005, 49/54 (90.7%) screened subjects were EGFR+, and 38 pts were enrolled. Pt characteristics: 26 (68.4%) males, 12 (31.6%) females; median age 63.5 years (39–82); median KPS 90 (70–100); 34 (89.4%) stomach, 4 (10.5%) GEJ; 18 (47.3%) gastrectomy; 13 (34.2%) adjuvant chemotherapy; 4 (10.5%) locally advanced disease, 34 (89.4%) metastatic disease; main metastatic sites: 19 (50%) lymphonodes, 12 (31.5%) liver, 4 (10.5%) lung, 8 (21.0%) peritoneal. Median number of treatment weeks was: 10 (1–46). Median dose intensity was: 5FU 100% (25–100), CPT11 100% (25–100) and cetuximab 100% (80–100). At the present time, 25 pts are assessable for response and 28 for toxicity. The OR (RECIST) were: 3 (12%) CR,11 (44%) PR, e.g. 56% CR + PR (95% CI: 37–75), 11 (44%) SD. The PFS at 3 months is 80% (95% CI: 64–96). Survival data are premature (73.6% of the pts are alive; median follow-up 3 months, range 1–12). Grade 3–4 toxicity (CTC v3.0) was: 15 (53.6%) neutropenia (1 pt died of febrile neutropenia), 1 (3.4%) thrombocytopenia, 2 (6.8%) hypertransaminasemia, 1 (3.4%) hyperbilirubinemia. Cutaneous toxicity was: 7 (25%) gr1, 11 (39.2%) gr2, 5 (17.8%) gr3. Conclusions: Combination of cetuximab and FOLFIRI appears to be active in gastric and GEJ adenocarcinoma, with a high response and disease control rate. This treatment has been well-tolerated; the major toxicity is neutropenia. No significant financial relationships to disclose.
Adjuvant chemotherapy with tegafur/uracil (UFT) for gastric cancer. A meta-analysis of centrally randomized clinical trials
Authors: Sakamoto J. , Tsuburaya A. , Morita S. , Matsui T. , Oba K. , Kodera Y. , Kobayashi M. , Yoshida K. , Nakao A. 
Published: March 2020

4033 Background: A consensus regarding standard adjuvant chemotherapy for curatively resected gastric cancer has not been obtained between Japan and Western world. In order to evaluate the effect of UFT which is the most frequently used in Japan over surgery alone control, a meta-analysis was performed investigating 4 clinical trials. Methods: After meticulous examination of each trial, trials with improper randomization using envelop method were excluded from the analysis. A total of 1503 patients, enrolled in four relevant trials (JCOG 8401, JCOG 8801, JCOG9206–2, and NSAS-GC) using UFT for chemotherapy and performed by central randomization, were determined eligible for the meta-analysis. The endpoint was overall survival and intent-to treat analysis was implemented. Results: The 5-year overall survival odds ratio was 0.70 (95%CI; 0.54–0.89). The treatment effect of oral UFT was shown to be statistically significant (p=0.01) over surgery alone therapy (n=1251). No significant heterogeneity between the trials was demonstrated (p=0.365). The 5-year overall survival odds ratio was 0.71(95%CI; 0.54–0.92). Conclusions: From these results of the present meta-analysis, it is strongly suggested that chemotherapy after surgery with UFT, can improve survival of the patients with curatively resected gastric cancer, and UFT should be considered as the standard postoperative adjuvant treatment for gastric cancer in Japan, where extensive gastrectomy with D2 lymph node dissection is implemented as a routine surgical procedure. No significant financial relationships to disclose.