bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cetuximab plus weekly oxaliplatin/5FU/FA (FUFOX) in 1st line metastatic gastric cancer. Final results from a multicenter phase II study of the AIO upper GI study group
Authors: Lordick F. , Lorenzen S. , Hegewisch-Becker S. , Folprecht G. , Wöll E. , Decker T. , Endlicher E. , Röthling N. , Fend F. , Peschel C. 
Published: March 2020

4526 Background: Cetuximab and oxaliplatin-5FU/FA are active in first-line metastatic colorectal cancer. Here we report on the final results from a trial assessing the efficacy of this combination in advanced gastric cancer. Methods: Pts received cetuximab 400mg/m2 at first infusion followed by weekly 250mg/m2 combined with the FUFOX regimen (oxaliplatin 50mg/m2 plus 5FU 2,000mg/m2 plus DL-folinic acid 200mg/m2 d1,8,15,22 qd36). The primary endpoint was response according to RECIST. Toxicity was reported according to NCI.CTC v3.0. Results: From 4/05 until 03/06 we included 52 pts at 7 study centers: 13 women and 39 men; median age 63 years (38–80). ECOG-PS 0/1/2 in 19/25/8 patients. Median number of involved organ sites 3 (1–5), 46% liver and 31% peritoneal involvement. EGFR was detectable by immunohistochemistry (IHC) in 59.5%. 5 pts (9.6%) died within 60 days after study inclusion, two deaths were treatment-related (1 hypersensitivity reaction, 1 septic diarrhea). One patient withdrew consent during the first infusion cycle and is therefore excluded from the following analyses. Reported grade 3/4 adverse events in 51 evaluable pts were: leukopenia 2.0%, febrile neutropenia 5.9%, thrombocytopenia 2.0%, nausea 5.9%, diarrhea 33.3%, fatigue 9.8%, sensory neuropathy 3.9%, hand-foot-syndrome 5.9%, skin-reactions 23.5%. Response is evaluable in 46 patients showing an overall response rate of 65.2% [CI 95%: 49.8; 78.6] including 4 complete and 26 partial responses. Eighteen (39.1%) responses have been confirmed. The reponse rate according to the EGFR-status is 76.5% in undetectable and 54.2% in detectable tumors. Intention-to-treat analysis reveals a time to progression (TTP) of 7.6 months [CI 95% 5.0; 10.1] and an overall survival (OS) of 9.5 months [CI 95%: 7.9; 11.1]. Conclusions: Cetuximab plus FUFOX is highly active in metastatic gastric cancer, irrespective of the EGFR detection by IHC. No significant financial relationships to disclose.
Serum proteomic profiling of advanced gastric cancer and identification of proteomic changes following response to epirubicin, cisplatin and capecitabine chemotherapy as diagnostic and predictive biomarkers
Authors: Helgason H. H. , Engwegen J. Y. , Cats A. , Boot H. , Kuiper M. , Zapatka M. , Joerger M. , Beijnen J. H. , Schellens J. H. 
Published: March 2020

4537 Background: Gastric cancer is the fourth most commonly diagnosed cancer and is the second leading cause of cancer death worldwide. Prognosis is highly dependent on stage at diagnosis making early diagnosis mandatory. By using SELDI - TOF mass spectrometry we compared serum protein profiles of gastric cancer patients with healthy controls and those of gastric cancer patients responding to first-line ECC chemotherapy with those with no response or early progressive disease. Methods: Serum from patients with advanced gastric cancer (GC) was obtained, according to a predefined schedule, prior to start of first-line epirubicin (50 mg/m2 day 1), cisplatin (60 mg/m2 day 1) and capecitabine (1,000 mg/m2 d1–14) chemotherapy (ECC) and serially before each treatment cycle every 3 weeks and analyzed by standardized SELDI-TOF MS/MS. Serum proteomic profiles of GC patients were compared with those of matched healthy controls and proteomic profile changes in responding and non-responding patients were analyzed. Results: In total 82 patients (mean age 57 years) were treated with mean 5 ECC cycles resulting in a response rate of 35%, mean time to progression of 7.1 months and mean overall survival of 12.4 months (95% CI: 10.7 - 14.1). By comparing GC patients and healthy controls we identified 18 m/z values that significantly (p < 0.00001) differentiated between the two groups (m/z 2.7 - 66.6 kDa). Comparison of responding and non-responding patients identified 2 proteins, m/z 3109 and 7559 Da, potentially predicting response (p < 0.001). Serial analysis of proteins changing differently during chemotherapy according to response will be performed. Conclusions: We identified 18 m/z values/proteins that highly (p < 1.0 E-05) discriminated between gastric cancer patients and healthy controls serving as candidate biomarkers of gastric cancer and 2 m/z values that significantly predicted response to chemotherapy. No significant financial relationships to disclose.
A randomized phase II trial of adjuvant chemotherapy with uracil / tegafur (UFT) and gemcitabine (GEM) vs. gemcitabine alone in patients with resected pancreatic cancer
Authors: Yoshitomi H. , Togawa A. , Kimura F. , Shimizu H. , Yoshidome H. , Miyazaki M. ,   Chiba study group of adjuvant chemotherapy for pancreatic cancer (CSAP)
Published: March 2020

4542 Background: GEM is now the standard therapy for patients with advanced pancreatic cancer (PC). However, there have been few randomized studies of adjuvant chemotherapy with GEM in patients with resected PC. Methods: Patients with invasive ductal pancreatic cancer who underwent radical surgery were enrolled. Within 8weeks after operation, pts were randomized to receive UFT and GEM (GU) or GEM alone (G). GEM was administrated at a dosage of 1g/m2 IV weekly X3 out of 4weeks and UFT at a dosage of 200mg/body/day orally continuously. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 1y disease free survival (DFS) rate and secondary endpoints included overall survival (OS) and side effects in both groups. Results: Between 05/02 and 12/05, 100 patients were randomized into the two arms of the trial (50 pts to GU and 50 to G). No pts were found to be ineligible. Pts characteristics were well balanced (GU/G) with regard to median age (62/63y), tumor status (T3+4 88/94%), nodal status (N positive 77/72%), histological residual tumor status (R0 76/68%). Until 03/06, 1y DFS rate was 50.3% in GU and 45.5% in G and there was no significant difference between two groups. The median OS was 20m in GU and 28m in G (Log rank test: N.S.). Grade 2 or more toxicities were observed in 67.3% of GU pts and 56.3% of G pts (N.S.). No grade 4 or more toxicity was observed in either groups. Leucocytopenia was the most frequently observed side effect in both groups (Grade 2 or more GU/G 49/46%). Conclusion: Preliminary results confirm the efficacy and safety of GEM based adjuvant chemotherapy for pts with resected PC, but addition of UFT with GEM dose not improve DFS as compared with GEM alone, so far. Final results will be presented at the meeting. No significant financial relationships to disclose.
RAS peptide vaccination in resected pancreatic cancer patients - persistence of anti tumour response and long term survival
Authors: Buanes T. , Bernhardt S. , Lislerud K. , Gladhaug I. , Moeller M. , Eriksen J. A. , Gaudernack G. 
Published: March 2020

4543 Background: K-RAS mutations are found in most adenocarcinoma of the pancreas, and targeting mutant RAS by vaccination may be of clinical importance. The present follow-up study was performed to determine whether or not mutant RAS specific T cells were still present in long term survivors seven to nine years after postoperative adjuvant vaccination with synthetic mutant RAS peptides Methods: During 1995–98, all together 23 patients were recruited into two clinical studies. The patients in CTN95002 (n = 10) were given a single mutant RAS peptide (100μg) corresponding to the RAS mutation identified in the patient’s tumor. Patients in CTN98010 (n = 13) were given a mixture of seven mutant RAS peptides, (700μg), corresponding to the most common mutations in pancreatic adenocarcinoma, in a 10 week vaccination regimen, using GM-CSF as an adjuvant, and boosters for an extended period. Immune responses were measured as skin reaction (DTH) and/or in vitro T-cell response. Blood samples from the five patients, still alive in 2006, were investigated by in vitro T-cell proliferation assay for immunological memory. Results: The five surviving patients were all immune responders during the primary vaccination period. Analysis of T-cell reactivity was performed seven (one patient), eight (one patient) and nine years (three patients) after resection/vaccination. Three patients still showed immune responses against the vaccine given previously. T cell reactivity against the Gly12Val mutation was observed in one patient receiving this peptide. In another patient a strong T cell reactivity against all seven peptides present in the vaccine, was observed. Conclusions: Long term survival beyond seven to nine years was only found in patients who primarily responded immunologically on the RAS-vaccination. Long term immunological memory can be induced by peptide vaccination. No significant financial relationships to disclose.
Modified FOLFOX in combination with docetaxel for patients with metastatic adenocarcinoma of the stomach or gastroesophageal junction: A multicenter phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: Al-Batran S. , Hartmann J. T. , Hofheinz R. , Mahlberg R. , Homann N. , Probst S. , Stoehlmacher J. , Fritz M. , Rethwisch V. , Seipelt G. , Jäger E. 
Published: March 2020

4545 Background: The combination of docetaxel, cisplatin, and fluorouracil (DCF) is clearly superior to CF in the treatment of patients (pts) with advanced gastric cancer (AGC). DCF is, however, associated with significant toxicity, including neutropenia, febrile neutropenia, diarrhea and mucositis. This study evaluated a biweekly, oxaliplatin-based modification of DCF. Methods: Pts with measurable, locally advanced or metastatic adenocarcinoma of the stomach or GE-junction and no prior chemotherapy received mFOLFOX (oxaliplatin 85 mg/sqm, leucovorin 200 mg/sqm, and fluorouracil 2.6 g/sqm via 24hr infusion) in combination with docetaxel 50 mg/sqm on day 1 every 2 weeks (FLOT-regimen). Prophylactic G-CSF was not administered. Overall response rate (RR) was the primary endpoint (power 80% to detect a RR of >40%) and toxicity profile the main secondary endpoint. The study was externally monitored according to GCP and data were reviewed by an independent safety board. Results: 59 pts (male, 41; female, 18) were enrolled. At the time of analysis, 53 pts were evaluable for toxicity and 51 pts for response. Median age was 60 (range, 29–76), median ECOG PS was 1, and almost all (93%) pts had metastatic disease. Of 51 pts, 2 had a CR and 25 pts attained a PR, adding to an overall RR of 53% (ITT-analysis). Stable disease was observed in 12 (23.5%) and progressive disease in 6 (11.8%) pts. Six (11.8%) pts were not evaluable for response. NCI-CTC grade 3 or 4 hematologic toxicity included leukopenia in 12 (22.6%), neutropenia in 23 (43%), and anemia in 2 (3.8%) pts. Febrile neutropenia was observed in 1 (1.9%) pt only. Other grade 3 or 4 toxicities included peripheral neuropathy in 4 (7.5%), nausea in 3 (5.7%), vomiting in 2 (3.8%) as well as diarrhea and fatigue in 5 (9.4%) pts each. No treatment related deaths were observed. Conclusions: FLOT is active and has a favorable toxicity profile in the treatment of pts with AGC. It may show activity also in perioperative treatment settings and may be considered as a useful treatment option for elderly pts. Survival data will be presented at the meeting. [Table: see text]
A randomized multi-center phase II trial of capecitabine (X) versus S-1 (S) as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer
Authors: Kang Y. , Lee J. , Min Y. , Lee K. , Zang D. , Ryoo B. , Kim J. , Park S. , Kang W. , Shin D. 
Published: March 2020

4546 Background: Although the combination chemotherapy is the standard of care for young patients (pts) with advanced gastric cancer (AGC), single agent chemotherapy may be a good alternative for elderly pts. Recent introduction of two new generation oral fluoropyrimidines, capecitabine and S-1, prompted us to investigate the activity and safety of these agents in elderly pts with AGC in a randomized multi-center phase II design. ( NCT00278863 ) Methods: Elderly chemo-naïve pts (= 65 years) with measurable metastatic or recurrent gastric cancer were randomly assigned to receive capecitabine (1,250 mg/m2 bid, D1–14 every 3 weeks, arm X) or S-1 (40∼60 mg bid according to BSA, D1–28 every 6 weeks, arm S). The primary endpoint was the response rate (RR). Results: From Oct 2004 to Apr 2006, 96 pts were enrolled. Excluding 5 pts who did not fit inclusion criteria, 91 pts were randomized to arm X (N=46) or arm S (N=45). Median age was 70.5 years for arm S and 71.0 years for arm X. Other clinical and tumor characteristics were well balanced across the two treatment arms. Among 44 assessable pts in arm X, 13 attained partial response (PR, 29.5%), 17 stable disease (SD, 38.6%) and 10 progressive disease (PD); 4 pts were not evaluable (NE). The corresponding disease responses in the 45 assessable pts in arm S were: 1 complete response (2.2%), 12 PR (26.7%), 18 SD (40.0%), 10 PD, and 4 NE. The incidence of grade 3–4 granulocytopenia was 6.8% in arm X and 4.8% in arm S. One episode of febrile neutropenia was observed in arm X. Grade 3–4 non-hematologic toxicities were as follows (arm X vs. S): asthenia (0% vs. 7.2%), anorexia (6.8% vs. 9.5%), diarrhea (2.3% vs. 0%), and HFS (6.8% vs. 0%). With a median follow up of 13.5 months (mo) for survivors (range, 8.1∼21.9), median time to progression and time to treatment failure were 4.8 mo (95% CI, 3.0–6.5) and 4.4 mo (3.6–5.3) for arm X and 4.2 mo (1.5–6.9) and 3.0 mo (1.5–4.5) for arm S. Median overall survival was 10.0 mo (8.0–12.0) for arm X and 7.9 mo (4.1–11.7) for arm S. Conclusions: Both treatments were active and tolerable as a 1st line treatment for elderly pts with AGC. No significant financial relationships to disclose.
Gastric adenocarcinoma in young patients: A population-based appraisal
Authors: Al-Refaie W. B. , Pisters P. W. , Chang G. J. 
Published: March 2020

4547 Background: While gastric adenocarcinoma is uncommon in young patients, reports of their outcomes remain inconsistent. We performed a population-based study of survival outcomes for gastric cancer in young adults (<45 years). Methods: Patients with gastric adenocarcinoma who underwent cancer directed surgery were identified from the Surveillance Epidemiology and End Results registry from 1991 to 2002. Patient demographics, tumor grade, AJCC stage and use of radiation were categorized by age to <45 years, 45 to 70 years and >70 years old. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis with log rank comparisons. Cox multiple regression analysis was performed to adjust for confounder effects. Results: A total of 20,830 patients were identified: 1,051 (5%) <45 years old [Grp 1], 8,456 (40.6%) 45–70 years old [Grp 2], and 11,323 (54.4%) >70 years old [Grp 3]. Grp 1 was more likely than Grp 2 to have advanced nodal disease (multinomial odds ratio [OR]=1.5 for N2 vs N0, 95% confidence interval [CI] 1.14–2.0, p=0.004; OR=2.0 for N3 vs N0, CI 1.4–3.0, p=0.0002) and more likely to have metastases at presentation (OR 1.5, p<0.00001). Stage-stratified 3-year cancer- specific survival [CSS] was not associated with age at diagnosis except for stage IV disease ( Table ). On Cox regression, young age did not impact survival (OR 0.95, CI 0.87–1.03, p=0.19). However, female gender, Asian race, earlier disease stage, lower grade, cancer- directed surgery and use of radiotherapy were predictors of better outcome (all p=0.003). Conclusions: Although young patients with gastric cancer in this population-based study present with more advanced disease, their stage-stratified cancer specific survival is similar to that of older patients. Stage-dependent, but not age-dependent, treatment should therefore be performed in young patients with gastric cancer. [Table: see text] No significant financial relationships to disclose.
Docetaxel, cisplatin and leucovorin/fluorouracil in first-line advanced gastric cancer and adenocarcinoma of the esophagogastric junction: Results of the phase II GASTRO-TAX-1 trial
Authors: Lorenzen S. , Weigert N. , Heinemann V. , Hentrich M. , Schuster T. , Seroneit T. , Röthling N. , Peschel C. , Lordick F. 
Published: March 2020

4561 Background: Phase II and III trials combining docetaxel, cisplatin and fluorouracil (DCF) every 3 weeks (wks) have shown superior efficacy but high rates of hematological toxicity in advanced gastric cancer. To reduce toxicity while containing the efficacy of DCF, we conducted a protocol using split doses of docetaxel (T), cisplatin (P), leucovorin (L), fluorouracil (F) (T-PLF). Methods: Chemo-naive patients (pts) with advanced gastroesophageal adenocarcinomas received T 50 mg/m2, P 50 mg/m2 day 1, 15, 29 and L 500 mg/m2 plus F 2,000 mg/m2 d1, 8, 15, 22, 29, 36 qd49. Because significant reductions to <80% of initial drug doses became necessary in 80% of pts, the regimen was amended after the first 15 pts. After the amendment the agents were administered as follows: T 40 mg/m2, P 40 mg/m2, L 200 mg/m2, F 2,000 mg/m2. The primary objective was the overall response rate (ORR) according to RECIST. Results: From 03/04 to 08/05 we included 60 pts: median age 53 yrs, (26–76); 24 pts had locally advanced tumors (LA) and 36 pts had metastatic disease (MET). Pts received a median of 2 (range 0–4) cycles. Reductions to <80% of drug doses were reported in 80% versus 60% of pts pre/post amendment. Reported adverse events were: neutropenia 23%, febrile neutropenia 5%, diarrhea 20%, nausea 8%, emesis 8% and fatigue 20%. The ORR according to RECIST was 46.6% (95%CI 33.3–61.4). Only 6.6% were primarily progressive. 23/24 pts with LA underwent secondary resection (96%). Complete resections (R0) were achieved in 87%. After a median follow-up of 25.5 months, median overall survival (OS) is 17.9 months (95%CI 11.5 -24.3). Median TTP is 9.4 months (95% CI 8.3–10.5). For pts with MET, median TTP is 8.1 months and median OS is 15.1 months. Conclusion: The T-PLF regimen is highly active, safe and has a favorable toxicity profile. [Table: see text]
Randomized phase II trial of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) for advanced gastric cancer
Authors: Shin D. , Lee S. , Park S. , Park J. , Cho E. , Lee J. , Lee W. 
Published: March 2020

4580 Background: Irinotecan, in combination with 5-fluorouracil (FU) or cisplatin, clearly demonstrated efficacy against gastric cancer. We compared the combination of irinotecan, leucovorin and FU (ILF) with cisplatin plus ILF (PILF) as first-line chemotherapy in patients with advanced gastric cancer (AGC). Methods: Patients with chemotherapy-naïve, histologically-confirmed, metastatic gastric adenocarcinoma were randomized to receive irinotecan 150 mg/m2 on day 1, leucovorin 20 mg/m2 and a 22-h infusion of FU 1,000 mg/m2 on days 1 and 2 (ILF), or ILF plus cisplatin 30 mg/m2 on day 2 (PILF). Treatment was repeated every 2 weeks until disease progression, unacceptable toxicity, or patients’ refusal. Primary endpoint was response rate which assessed every 4 cycles of chemotherapy. With a single-stage phase II design, the required number of patients was at least 35 per each arm. Results: Of 91 patients registered, 46 patients were treated with ILF and 44 with PILF. For both arms, 635 chemotherapy cycles were delivered (median, 6 for ILF and 8 for PILF; p=0.46). Both ILF and PILF were generally well tolerated. However, PILF was associated with, although statistically insignificant, substantially more grade 3 or 4 toxicities than ILF (46% and 38%, respectively). In the ILF and PILF arm, 11% and 25% of patients, respectively, discontinued treatment because of toxicity. Treatment duration was similar for both arms (4.3 for ILF v 5.6 months for PILF; p=0.13). Four patients died during treatment: one in the ILF arm and 3 in the PILF arm. The objective response rate was 37% for both arms. Disease control (response plus stable disease) was achieved in 59% and 73% (p=0.02) of patients treated with ILF and PILF. There were no significant differences in therapeutic efficacy between ILF and PILF with respect to progression-free (4.8 v 6.2 months; p=0.60) and overall (10.9 v 10.4 months; p=0.93) survival. Conclusions: Both ILF and PILF appear to be active as first-line chemotherapy for AGC, with acceptable safety profiles. Given the comparable efficacy results, ILF could be a reasonable standard chemotherapy for untreated AGC patients. No significant financial relationships to disclose.
Somatic mutations of EGFR signal transducers and expression of tumor suppressor PTEN in biliary tract carcinoma
Authors: Aglietta M. , Pignochino Y. , Cavalloni G. , Sarotto I. , Penachioni J. , Zanon C. , Migliardi G. , Piacibello W. , Risio M. , Bardelli A. , Leone F. 
Published: March 2020

4582 Background: Biliary tract carcinomas express EGFR and are potential candidates to EGFR target therapies. We recently described somatic mutations of EGFR that can enhance MAPK or Akt activation (Clin Cancer Res, 2006). Some of them are identical to those previously reported to confer sensitivity to some tyrosine kinase inhibitors (TKIs) like erlotinib or gefitinib in lung cancer. Here we report a molecular analysis of EGFR transducers potentially involved in TKI response. Methods: In 49 samples of biliary tract carcinoma we performed mutational analysis of exons from 18 to 21 of EGFR, exons 9 and 20 of phosphatidylinositol 3’-kinase (PI3K), exon 2 of K-Ras, exon 15 of B-Raf and exons from 5 to 8 of PTEN. Nuclear PTEN expression was analyzed by immunohistochemistry and the expression in cancer cells was compared to that of normal cholangiocites. Results: Mutations of EGFR have been detected in 7 out of 49 samples (14.3%). One of them was a new stop-codon mutation. Five hotspot mutations of PI3K (codon 545, 546, 1048 and 1059) were found in 4 cases (8.2%); 3 cases (6.1%) had single mutations in K-Ras and 4 (8.2%) had the V599E mutation in B-Raf. In some samples, mutations of multiple trasducers were present simultaneously. PI3K mutations were significantly more frequent in EGFR mutated samples compared to wild type (28% vs. 4.7% respectively, p<0.05). A single F271L mutation of PTEN was observed (2%). We did not find loss of nuclear PTEN in biliary tract carcinoma cells; rather, a stronger labelling intensity (score 2+ or 3+) was present in biliary tract carcinoma compared to normal cholangiocites (score 1+). Moreover, the median percentage of PTEN labeled nuclei in tumor cells was 31.8%, but in samples with activating EGFR mutation was 60%, suggesting that a compensatory change in the level of the phosphatase might counteract the EGFR activition. Conclusions: These results corroborate our previous finding of EGFR pathway activation in EGFR mutated biliary tract carcinoma and suggest that an accurate analysis of the entire series of EGFR transducers may be done before planning treatments with TKIs. No significant financial relationships to disclose.