bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic treatment of irinotecan-induced diarrhea with neomycin (a randomized, placebo-controlled, double-blind study)
Authors: Mathijssen R. H. , De Jong F. A. , Kehrer D. F. , Van Schaik R. H. , Verweij J. , Sparreboom A. , De Jonge M. J. 
Published: March 2020

3626 Background: Delayed-type diarrhea is a common side-effect of irinotecan, and is associated with a bacterial-mediated formation of the active irinotecan metabolite SN-38 from its glucuronide conjugate in the intestines. We hypothesized that concomitant administration of the aminoglycoside antibiotic neomycin would diminish exposure of the gut to SN-38, ameliorating the incidence of diarrhea. Methods: Patients were treated with irinotecan in a randomized, placebo-controlled, double-blind trial. In arm A, patients received irinotecan (350 mg/m2 i.v. for 90 minutes once every 3 weeks) combined with neomycin (660 mg orally 3 times daily for 3 consecutive days, starting 2 days before chemotherapy). In arm B, patients received the same irinotecan regimen with placebo. To detect a 50% reduction to less than grade 2 diarrhea (power=.80; P=.05), 60 patients had to be studied. Blood samples for additional pharmacokinetic and pharmacogenetic analyses were obtained after separate informed consent. Results: Sixty-two patients were evaluable for toxicity analysis. Relevant baseline patient characteristics (P>.06), SN-38 plasma concentrations (P=.80; N=43), and UGT1A1*28 genotype status (P=.58; N=52) were similar in both arms. Distribution, severity, and duration of diarrhea did not differ significantly between both arms (P>.32), although grade 3 diarrhea tended to be less frequent in the neomycin arm (45% reduction; P=.19). Grade 2 nausea was more common in this arm (39% vs. 9%; P<.01). The presence of at least one UGT1A1*28 allele was strongly related to the incidence of grade 2–3 diarrhea (69% vs. 34%; P=.01). Conclusions: Our results do not suggest a role for neomycin in the prophylactic treatment of irinotecan-induced diarrhea. In addition, neomycin does not influence systemic SN-38 pharmacokinetics. Also, it is suggested that each patient’s UGT1A1*28 genotype status could be used as a prospective screening tool to prevent severe diarrhea. No significant financial relationships to disclose.
Phase III trial comparing initial chemoradiotherapy (intermittent cisplatin and infusional 5-FU) followed by gemcitabine vs. gemcitabine alone in patients with locally advanced non metastatic pancreatic cancer: A FFCD-SFRO study
Authors: Chauffert B. , Mornex F. , Bonnetain F. , Triboulet J. P. , Bouche O. , Rougier P. , Bosset J. F. , Aparicio T. , Masskouri F. , Bedenne L. 
Published: March 2020

4008 Background: The GITSG studies have shown a greater survival after 5 FU-based chemoradiotherapy (CHRT) than radiotherapy or polychemotherapy alone in patients (pts) with locally advanced non metastatic pancreatic cancer. This randomized trial evaluated whether initial CHRT adds to modern gemcitabine in term of Overall Survival (OS). Methods: Pts with WHO status 0–2, proven adenocarcinoma of the pancreas, without metastasis at CT-scan, and deemed non resectable, were randomized 1:1 between CHRT ( 60 Gy in 6 weeks, 2 Gy/fraction, concomitant with 5-FU, 300 mg/m2/24 h as a continuous infusion, day 1–5 every week and cisplatin, 20 mg/m2/d, day 1–5 at week 1 and 5) or gemcitabine (G) (1000 mg/m2 weekly 7q8w) as induction treatment. Maintenance treatment was G (1000 mg/ m2 weekly 3q4w) in both arms until progression or limiting toxicity. Stratification criteria were: center, WHO status and initial surgery. It was required to include 176 pts to detect an expected change in median OS from 6 to 12 months (bilateral α = 1% and β = 10%). Intent to treat survival analysis used the Logrank test. Results: Between 03/00 and 07/05, 59 pts were randomized to CHRT and 60 to G. Median follow-up at the 05/05 was 16 months. Pt characteristics were well balanced (CHRT/G) with mean age (60.1/62.7 year), sex ratio (1/ 1.4) and WHO status ( 0–1: 88%/73%, 2: 9%/23%). During the induction phase, more than 75% of the planned dose was completed in 81.4% of pts for radiotherapy, 52.5% for 5-FU and 50.8% for cisplatin and 76.7% of pts in the G arm. In CHRT and G arms, OS at 6 and 12 months were respectively 78/82% and 24/51%, with a median survival of 8.4/14.3 months (stratified log-rank p = 0.014). CHRT or G related toxicities during induction phase were grade 3/4 leukopenia (17%/10%), thrombopenia (8.5%/0%), non-haematological toxicity (37%/ 17%) with diarrhea (7%/0% ), cutaneous toxicity (0%/3%). One treatment-related death was observed in the CHRT arm (aplasia). Conclusion: Study was stopped before the planned inclusion due to lower survival with initial CHRT when compared to G alone. Reasons explaining this difference are under investigation. No significant financial relationships to disclose.
Tumor VEGF expression and serum VEGF levels are independent prognostic factors in curatively resected gastric cancer patients
Authors: Pera M. , Vidal O. , Elizalde J. , Soriano A. , Volant A. , Palacin A. , Molina R. , Castells A. , Pique J. , Metges J. 
Published: March 2020

4021 Background: Increased serum and/or tumor vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) have been shown to predict poor survival in several neoplasms, but their prognostic value in gastric cancer (GC) remains unknown. Methods: Serum VEGF (S-VEGF) and uPA concentrations were measured by commercially available ELISA in 20 healthy controls and 97 GC patients (70% I-II stages) before an R0 gastric resection. Tumor expression of VEGF and uPA were assessed by immunohistochemistry. Additional variables, including demographic, histological and therapeutic data were also evaluated. Univariate (Kaplan-Meier, log-rank test) and multivariate (Cox regression) analyses were performed to select prognostic factors regarding survival and tumor recurrence. Results: S-VEGF, but not uPA levels were significantly higher in GC patients than in controls. After a mean follow-up of 47 ± 3 months, the probability of cancer-related survival at 2, 5, and 10 years was 86%, 69% and 59%, respectively. Univariate analysis identified tumor VEGF expression (p=0.001) and high (> 289 pg/ml) S-VEGF levels (p=0.045), along with pTMN stage, grade of curability, perineural invasion, lymph node ratio, and extent of lymphadenectomy as variables associated with cancer-related survival. The mean disease-free survival was 20 ± 3 months, the probability of tumor recurrence being 78%, 62% and 62% at 2, 5 and 10 years, respectively. Prognostic variables for recurrence were the same as those identified for survival. Multivariate analysis identified tumor VEGF expression and high S-VEGF levels as independent prognostic survival factors. Conclusions: After a long follow-up, tumor VEGF expression and S-VEGF levels are independent prognostic factors for recurrence and survival in curatively resected gastric cancer patients. Such markers for increased angiogenic activity might help to identify patients at high risk of recurrence that could mostly benefit from adjuvant therapies. It is tempting to speculate that trials assessing the potential benefit of a.ntiangiogenic agents might be particularly warranted in patients with resected GC and a highly angiogenic phenotype. No significant financial relationships to disclose.
Differences in the patterns of presentation and treatment between proximal and distal gastric cancers
Authors: Wilkinson N. W. , Howe J. , Patel-Parekh L. , Smith B. , Scott-Conner C. , Donohue J. 
Published: March 2020

4022 Background: While the overall incidence of gastric cancer has declined in the United States, the incidence of proximal gastric cancers has increased. Understanding the differences between proximal and distal gastric cancer, may enable us to identify important risk factors and treatment patterns. Methods: Data on 6099 patients diagnosed with gastric adenocarcinoma were collected as a Patient Care Evaluation under the auspices of the American College of Surgeons Commission on Cancer. Clearly defined proximal and distal cancers were compared using the Pearson chi-square test and logistic regression. Results: The proximal cancer group included 1924 patients (87% cardia; 13% fundus) and the distal cancer group included 1312 patients (85% antrum; 15% pylorus). Proximal gastric cancers occurred more often in men (p<0.0001), whites (compared to Black, Hispanic, Native American and Asian races) (p<0.0001), and at younger age (p<0.0001) compared to distal cancers. Risk factors for proximal presentation included tobacco use (Hazard ratio (HR) 1.9, p= 0.002) alchohol use (HR 1.5, p= 0.038) and Barretts (HR 2.7, p<0.0001). Risk factors for distal presentation included H. Pylori (HR 2.3, p= 0.001). Despite increased use of multi-modality therapy, fewer proximal gastric cancers underwent resection compared to distal cancers (p<0.0001). Conclusions: Different risk factors can be identified for proximal and distal gastric cancers, which can impact on risk reduction, screening efforts and help define the pathogenesis of gastric cancer. While proximal cancer patients receive more aggressive multimodality treatments, including adjuvant and neoadjuvant therapy, fewer undergo surgical resection. Long term survival based upon proximal and distal tumor differences will be explored when follow-up data become available.Key Words: gastric adenocarcinoma, proximal gastric cancer, distal gastric cancer, risk factors, treatment. [Table: see text] No significant financial relationships to disclose.
Impact of pre-operative chemoradiotherapy on post-esophagectomy morbidity and mortality
Authors: Rizk N. P. , Bains M. , Flores R. , Park B. , Minsky B. , Ilson D. , Rusch V. 
Published: March 2020

4025 Background: While multimodality therapy prior to surgical resection for locally advanced esophageal cancer is increasingly utilized, there remains the perception in the literature that its use may contribute to increased peri-operative morbidity and mortality. The purpose of this study was to compare our experience with the use of pre-operative chemoradiation with surgery (CRT) to patients who underwent surgery alone (S). Methods: We performed a retrospective review of a prospectively maintained database of all patients in our institution who underwent either (S) or (CRT) between 1/96 and 5/05. Data collected included demographics (age, sex), co-morbidities (cardiac, pulmonary, diabetes), pre-operative treatment details (chemotherapy type, radiation dose), procedure type, post-operative complications (pneumonia, anastomotic leak), length of stay (LOS), and hospital mortality. Statistical analysis included chi-square analysis for categorical variables and analysis of variance for continuous variables, and multivariate analyses was done using a logistic regression model. Results: There were 701 patients who were appropriate for this analysis, 332 (47.3%) (CRT) and 369 (52.7%) (S). 76% of CRT patients received 5040cGy of radiation and 90% received concurrent cisplatin based chemotherapy. CRT patients were younger (p<0.001) and more often male (p=0.003). Univariate analysis indicated a similar incidence of pneumonia (p=0.78), leak rate (p=0.41), hospital length of stay (0.97), and hospital mortality (0.48). Multivariate analysis, controlling for demographics, co-morbidities, procedure type, and tumor location showed no significant difference in hospital mortality (p=0.84). Conclusions: The use of CRT does not appear to result in increased peri-operative morbidity or mortality. No significant financial relationships to disclose.
Dihydropyrimidine dehydrogenases (DPYD), and cytidine-deaminase (CDA) gene polymorphisms as genomic predictors of clinical outcome in resected gastric cancer patients (GCP) treated with fluoropyrimidine-based adjuvant chemotherapy
Authors: Grau J. J. , Monzo M. , Muñoz C. , Bombi J. A. , Domingo-Domenech J. , Jansa S. , Lema L. , Palmero R. 
Published: March 2020

4052 Background: Single nucleotide polymorphisms (SNPs) of DPYD gene induces DPD deficiency resulting in decreased activity of 5-fluorouracil derivatives in treatment of colorectal cancer patients (pts). In GCP has not been previously analysed. Methods: We analysed paraffin-embedded biopsies from 50 consecutive resected GCP who received adjuvant chemotherapy with four cycles of Mitomycin C (MMC), 20 mg/m2 iv day 1 plus oral Tegafur (TG), 500 mg/m2 day 1 to day 45 every six weeks, for SNPs of genes DPYD1 (A/G; Ile/Val), DPYD2 (C/T; Arg/Cys) and CDA (A/C; Lys/Gin). The status of alleles (wild type or at least 1 polymorphism) was correlated with outcome, overall survival (OS) and toxicity. Results: The status of SNPs frequencies according to the classification between wild type/non-wild type, were 36/14 in DPYD1; 26/24 in DPYD2; and 17/23 in CDA or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow-up, 18 pts died of tumor relapse, (7 in peritoneum and 11 in distant organs). Difference in survival was observed in DPYD1 pts only, for non wild-type over wild-type (p = 0.0283) and in any of the 3 genes tested heterozygous over homozygous pts (p = 0.0463). In 10 pts (20%) total dose was reduced by toxicity (5 diarrhea, 2 neutropenia, 2 hepatotoxicity, 1 vomiting), only 3 of them were homozygous. Conclusions: SNPs of DPYD1, DPYD2 and CDA predict outcome, survival and toxicity of GCP treated with 5-FU-based adjuvant chemotherapy. No significant financial relationships to disclose.
CONKO-101: Results of a multicenter phase II study of an outpatient regimen consisting out of gemcitabine, 5-FU (24h CI), folinic acid and cisplatin for patients with inoperable esophageal cancer
Authors: Stieler J. M. , Hilbig A. , Pelzer U. , Roll L. , Dörken B. , Riess H. , Oettle H. 
Published: March 2020

4066 Background: Standard therapy for inoperable esophageal cancer is a combination of cisplatin and 5-FU combined with radiation for locally advanced stages. As gemcitabine shows synergy with cisplatin and 5-FU, we evaluated the combination of cisplatin 30 mg/m2 (90 min), Gemcitabine 1000 mg/m2 (30 min), FS 200 mg/m2 (30 min) and 5-FU 750 mg/m2 24h CI) d1,8 q d22 for patients with inoperable esophageal cancer. For locally advanced stages, patients received sequential radiochemotherapy with 5-FU CI. Methods: 89 (75 m/14 w) pts. were included into this multicentrical phase 2 study. 58 had SCC, 30 AC, 1 pt. had undifferentiated carcinoma. Median age was 61 (22–86), Median KI 90 (60–100). 2 pts. had stage IIa, 4 stage IIb, 30 stage III, 16 stage IVa and 37 stage IVb. Results: 71 pts. are so far evaluable for response and 84 for toxicity. 2 pts. (2.8%) had CR (1 pathologically confirmed), 27 pts. had PR (38.1%), 33 pts. had SD (46.5%) and 9 pts. had PD (12.6%) as best response. MS was 10.7 months (13.1 for stage II/III and 9.1 for stage IV). Median TTP was 6 months, and PFS was 6 months. Observed toxicity was low and predominantly hematologic with Leukopenia Grade III/IV in 10% of cycles, Hb Grade III/IV in 5.3% of cycles and Thrombopenia Grade III/IV in 2.4% of cycles. Conclusion: This regimen is well tolerable and can easily be applied on an outpatient base. The remission rates and survival data are within the range previously reported in other phase II studies. No significant financial relationships to disclose.
Mature data on capecitabine (X) + fractionated cisplatin (P) as first-line therapy in patients (pts) with advanced gastric carcinoma (AGC)
Authors: Jin M. , Shen L. , Hu B. , Yu J. , Wen Z. , Su Y. , Wang B. , Chen L. , Ying H. , Chen L. 
Published: March 2020

4075 Background: Gastric cancer is one of the most common malignancies in Asia with an adjusted mortality rate above 20/100,000 population. 5-FU + fractionated P is a standard treatment for AGC in China. In a Korean study by Kim et al., X + P produced a response rate of 55% in pts with previously untreated AGC. Here we present mature efficacy/safety results in Chinese pts with AGC. Methods: 154 pts of a planned population of 120 pts were enrolled between Jun 2002 and Aug 2004. All had measurable AGC (WHO), Karnofsky performance status ≥60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was permitted. Pts received × 1000 mg/m2 orally bid on days 1–14 + P 20mg/m2/day i.v. on days 1–5, every 3 weeks for 6 cycles. The primary endpoint was time to disease progression (TTP). Results: Baseline characteristics of the 141 evaluable pts (104 men, 37 women) are: median age 54 years (range 23–80), main sites of metastases: lymph nodes 45%, liver 40%, stomach 18%, skin 6%, other 6%, lung 5%, abdomen 4%. The overall response rate was 36%, including 13 complete responses and 38 partial responses. After a median follow-up period of 12 months, the median TTP is 9 months (95% CI, 9–12 months) and the median overall survival is 12 months (95% CI, 12–15 months). Median treatment duration was 6 cycles (range 3–6). The most common treatment-related clinical adverse events (all grades >5%) were: hand-foot syndrome (HFS) 25%, leucopenia 13%, and SGOT abnormality 12%. The most commongrade 3 adverse events were SGPT abnormality 3%, HFS 2%, and anemia 2%. There were no grade 4 adverse events. Most grade 3 adverse events improved or resolved after treatment or interruption except in 1 pt with anemia who withdrew after 2 cycles. Conclusions: X combined with fractionated P is highly active and very well tolerated as first-line treatment for AGC, with comparable results to 5-FU + P. No significant financial relationships to disclose.
SP1049C as first-line therapy in advanced (inoperable or metastatic) adenocarcinoma of the oesophagus: A phase II window study
Authors: Armstrong A. , Brewer J. , Newman C. , Alakhov V. , Pietrzynski G. , Campbell S. , Corrie P. , Ranson M. , Valle J. W. 
Published: March 2020

4080 Background: SP1049C (a block co-polymer incorporating doxorubicin) has demonstrated broad in vitro activity and superior anti-tumour activity in 9/9 in vivo animal tumour models compared to doxorubicin. Methods: Chemotherapy- or radiotherapy-naïve patients with measurable, inoperable, recurrent or metastatic adenocarcinoma of the oesophagus; KP ≥60; normal cardiac LVEF; adequate swallowing and adequate renal, hepatic and bone marrow function were eligible. SP1049C 75mg/m2 IV 30-minute infusion was given q3w, for up to 6 cycles. Radiological response was assessed after cycles 2, 4 and 6. Upon disease progression (PD) patients were offered standard chemotherapy. QoL (by QLQ-C30 and QLQ-OES24 questionnaires), toxicity, disease-related symptoms and cardiac function were also prospectively assessed. Results: From February 2002 to December 2004, 21 patients (all male), median age 62 years (range 38–78) with stage 3 (n = 1) of stage IV (n = 20) disease were enrolled. Response rate (WHO criteria) in 19 patients eligible for efficacy analysis (radiologically re-assessed after ≥2 cycles of treatment) included: PR 9/19 (47%), SD (8/19) 42% and PD (2/19) 11% by investigator assessment (confirmed PR 41%, unconfirmed PR 12% and SD 29% by independent review, RECIST criteria). One responding patient underwent salvage resection of a pT2N0 (Stage 2A) tumour. All patients are evaluable for toxicity. Toxicity (Gd 1–2/3–4, by patient) included: neutropaenia 24%/62%, leucopaenia 19%/29%, anaemia 38%/5% and thrombocytopaenia 9.5%/0% (resulting in 9 (43%) patients being dose-reduced to 55 mg/m2 at cycle 2), nausea 81%/19%, vomiting 62%/24%, anorexia 52.4%/14%, lethargy 81%/14%, febrile neutropaenia -/29%, mucositis 48%/5%, and Gd 1–2 alopecia in 67%. Grade I cardiotoxicity (fall in LVEF by 10–19% from baseline, CTC v2.0) was seen in 4 (19%) patients. The median overall survival (all patients) is 10 months; four patients received 2nd-line chemotherapy. Conclusions: SP1049C appears to have activity in monotherapy in this patient group and combination studies with other active agents are warranted. [Table: see text]
The prognostic role of the WHO classification, urinary 5-hydroxyindoleacetic acid (u5HIAA) and liver function tests (LFTs) in metastatic neuroendocrine carcinomas (NECs) of the gastroenteropancreatic (GEP) tract
Authors: Formica V. , Norman A. R. , Cunningham D. , Wotherspoon A. , Sirohi B. , Oates J. , Chong G. 
Published: March 2020

4092 Background: The aim of this study was to assess the prognostic value of the revised neuroendocrine tumour (NET) WHO classification (2000) and to identify additional prognostic factors. Methods: 119 pts with metastatic NET arising from the GEP tract treated at the RMH were eligible for this retrospective study. All were classified according to WHO guidelines into well-differentiated and poorly-differentiated neuroendocrine carcinomas (WDNEC and PDNEC). Demographic, clinical and biochemical data at diagnosis were recorded as potential prognostic factors. The hazard ratios (HRs) between subgroups of patients were estimated by Cox regression analysis; survival curves were generated by Kaplan-Meier method. Approval for the study was obtained from the local ethics committee. Results: 8% of pts had PDNECs, 92% had WDNECs. Histological differentiation had the most impact on overall survival (OS) (HR = 4.02, 95%CI 1.26–12.82, p = 0.02, using WDNECs as the reference). In a WDNEC-restricted multivariate analysis, significantly abnormal LFTs and elevated u5HIAA were independent prognostic factors for survival (HR = 2.65, 95% CI 1.33–5.30, p = 0.006 and HR = 2.51, 95% CI 1.35–4.63, p = 0.003, respectively). Radiological evidence of liver metastases was not predictive of survival. These variables were used to create a WDNEC-specific prognostic model (low-risk = both normal, intermediate-risk = one abnormal, high-risk = both abnormal) (see table ). Statistically distinct median OS (mOS) were identified for each of the 3 risk groups. High-risk WDNECs had similar poor survival to PDNECs. Conclusion: This analysis supports the prognostic value of the WHO classification for metastatic NETs arising from the GEP tract. Risk stratification using readily available u5HIAA and LFTs may give additional prognostic information for WDNECs, although these observations need to be confirmed in an independent dataset. [Table: see text] No significant financial relationships to disclose.