bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group
Authors: Moehler M. H. , Thuss-Patience P. , Arnold D. , Grothe W. , Stein A. , Seufferlein T. , Mantovani Loeffler L. , Geissler M. , Hofheinz R. D. , Schmoll H. 
Published: August 2020

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]
Pathological features of advanced gastric cancer (GC): Relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial
Authors: Bang Y. , Chung H. , Xu J. , Lordick F. , Sawaki A. , Al-Sakaff N. , Lipatov O. , See C. , Rueschoff J. , Van Cutsem E. 
Published: August 2020

4556 Background: HER2 positivity is thought to be a negative prognostic factor in GC, correlating with poor survival rates. Reported HER2-positivity rates in GC have varied widely (6–35%). The ToGA trial is evaluating the addition of trastuzumab (Herceptin) to chemotherapy in HER2-positive advanced GC. It is the first randomised Phase III trial to provide prospective information on HER2-positivity rates in GC. Enrollment is complete, with 3,883 patients screened in 24 countries. The pathological features of GC and the relationship with HER2 positivity will be examined. Methods: Advanced GC tumour samples were centrally screened by immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridisation (FISH; PharmDx) in parallel. A HER2-scoring system modified from the protocol in breast cancer (BC) was used: a score of IHC 3+ and/or FISH positive was defined as HER2 positive. Results: Final data showed an overall HER2-positivity rate of 22.1% evaluated from 3807 patients. The HER2-positivity rate was similar between Europe (23.6%) and Asia (23.5%). HER2-positivity rates were higher in gastro-oesophageal junction (GEJ) than stomach cancer (33.2% vs 20.9%; p<0.001) and in intestinal than diffuse/mixed cancer (32.2% vs 6.1%/20.4%; p<0.001). This is reflected in above-average HER2-positivity rates in countries with the highest GEJ:stomach cancer ratios (France 0.56 [HER2 positivity 26.9%]; Germany 0.53 [23.7%]; UK 0.33 [25.8%]) and intestinal:diffuse cancer ratios (UK 3.4 [HER2 positivity 25.8%]; Australia 2.6 [32.8%]; Japan 2.8 [27.8%]). The modified HER2-scoring system showed concordance between IHC and FISH results of 87.5%. In BC most IHC 0/1 samples are FISH negative but, in ToGA, the frequency of IHC 0/1 samples testing FISH positive was almost as high as IHC 2/FISH-positive samples (23% vs 26%). Conclusions: The overall HER2-positivity rate in advanced GC in ToGA is 22.1%. Variations in tumour location and type mostly explain the difference in HER2-positivity rates between countries. Efficacy data will enable further evaluation of the clinical significance of HER2 IHC and FISH scoring patterns. [Table: see text]
Polymorphisms in epidermal growth factor (EGF) and proteinase activated receptor 1 (PAR-1) associated with tumor recurrence in localized adenocarcinoma (EA) of the esophagus treated with surgery alone
Authors: Lurje G. , Leers J. M. , Pohl A. , Oezcelik A. , Zhang W. , Yang D. , Hagen J. A. , DeMeester S. R. , DeMeester T. R. , Lenz H. J. 
Published: August 2020

4564 Background: Tumor angiogenesis is a well-recognized aspect of human cancer biology and is mediated at least in part by EGF and PAR-1, which in turn may impact the process of tumor growth and progression. Systemic tumor recurrence after curative resection continues to be a significant problem in the management of patients with localized EA. Further, it is being increasingly recognized that esophageal squamous cell carcinoma and EA are separate and distinct disease groups and need to be considered individually. We therefore designed a large retrospective study of EA patients to identify novel molecular markers of prognosis to better define tumor stage and progression, and help to define novel targets, as well as surrogate-endpoints of disease progression and response to therapy. Methods: Between 1992 and 2005 normal esophageal tissue samples from 239 patients with localized EA treated with surgery alone were obtained at University of Southern California medical facilities. The median follow-up was 3.2 years. 114 out of 239 (48%) patients had tumor recurrence, with a probability of 5-year recurrence of 0.62 ± 0.04. DNA was isolated from formalin-fixed paraffin-embedded specimens and 10 angiogenesis related and functional gene polymorphisms were analyzed using a PCR-RFLP and 5´-end [γ-33P] ATP-labeled PCR method. Results: PAR-1 -506 ins/del (p-value=0.003; log-rank test) and EGF +61 A>G (p-value=0.034; log-rank test) are adverse prognostic markers in univariate analysis. After adjusting for covariates (gender, T1-, N-category, type of surgery) in the multivariable model, "high-expression" variants of PAR-1 (any insertion allele) (RR: 1.81; adjusted p-value = 0.011) and EGF (A/A) (RR: 1; adjusted p-value=0.035) remained significantly associated with time to recurrence, compared to other genotype combinations of PAR-1 (RR: 1) and EGF (RR: 0.65). Conclusions: This study supports the role of functional EGF and PAR-1 polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence. Prospective and biomarker-embedded clinical trials are needed to validate our findings. [Table: see text]
Phase II study of cetuximab plus weekly cisplatin and 24-hour infusion of high-dose 5-fluorouracil and leucovorin for the first-line treatment of advanced gastric cancer
Authors: Yeh K. , Hsu C. , Hsu C. , Lin C. , Shen Y. , Wu S. , Chiou T. , Chao Y. , Cheng A. 
Published: August 2020

4567 Background: Cisplatin-HDFL regimen, using weekly 24-hour infusions of cisplatin and high-dose 5-fluorouracil (5-FU) and leucovorin, is commonly used in Taiwan for patients with advanced gastric cancer (GC), showing an overall response rate of approximately 60% (95% CI: 45%-76%) [J Clin Oncol (Suppl) 2006; 24(18S): A14063 ]. We have demonstrated that cetuximab is cytotoxic to human GC cells, and has a chemosensitizing effect for cisplatin and 5-FU in GC cells [Proc AACR 2006; 47: A1233]. Methods: All patients had pathologically confirmed metastatic/ recurrent chemonaive GC, at least 1 measurable lesion, a fasting serum triglyceride level > 70 mg/dl, WHO PS 0/1/2, adequate hepatic, renal, and bone marrow functions. Cetuximab 400 mg/m2 was given as 2h infusion, initially (i.e., D1 of cycle 1); and followed by weekly 1h infusion of 250 mg/m2 (i.e., D8, D15, D22 of cycle 1, and D1, D8, D15, D22 of cycle 2). Cisplatin 35 mg/m2 was given as a 24h infusion, admixing with 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 (HDFL), D1, D8. A 24h infusion of HDFL was given on D15. Cycles were repeated every 28 days, and response evaluation was performed every 2 cycles & at the end of protocol treatment. The primary end-point was confirmed objective response rate (RR) by RECIST. Results: Between Dec. 2005 and Nov. 2008, 35 patients (M:19, F:16) with a median age of 56 (40–74) were enrolled and evaluable for response assessment. The overall RR was 68.6% (51–83%, 95% C.I.) with 1 CR and 23 PRs. Among a total of 269 cycles (median: 7, range: 2 to 22+ cycles) given, Gr3/4 neutropenia, infection, and hepatic toxicity developed in 6.0%, 4.8%, and 0.74% of 269 cycles, respectively. Two patients have developed acute hepatitis B flare-up among seven HBsAg (+) carriers, and were well controlled by lamivudine. Gr1, Gr2, and Gr3 acne- like rashes have developed in 57.1%, 31.4%, 5.7%; and Gr1, Gr2, Gr3 paronychia have developed in 40.0%, 8.6%, and 2.9% of 35 patients, respectively. Median PFS (range: 3 to 22+ months) and median OS (range: 3 to 35+ months) was11.0 and 14.5 months, respectively. Conclusions: Cetuximab plus infusional cisplatin-HDFL is a highly effective regimen with low toxicity and favourable survival in the first-line treatment of advanced GC. No significant financial relationships to disclose.
Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms in an Omani population
Authors: Al-Moundhri M. S. , Al-Nabhani M. , Burney I. , Rizvi A. , Al-Farsi A. , Al-Bahrani B. 
Published: August 2020

4568 Background: VEGF plays a central role in the angiogenesis, tumor growth and metastasis. VEGF gene polymorphisms at various loci and gastric cancer (GC) risk predisposition and their prognostic significance were studied previously with controversial results Methods: We analyzed three VEGF polymorphisms (+405 G>C, -460T>C, and +936C>T) by extraction of genomic DNA from peripheral blood of 130 GC patients and 130 control subjects followed by VEGF genotyping using PCR-RFLP analysis and the determination of the polymorphisms GC risk predisposition and their prognostic significance Results: There was no significant association between the VEGF polymorphisms and gastric cancer risk. There was a significant correlation between +405 C/C genotype and poor tumor differentiation (p=0.007) and lymph node metastasis (p=0.03) and 460T/T genotype and poor differentiation (p=0.03) with statistical trend for lymph node involvement (p=0.05). VEGF gene polymorphisms had no significant effect on survival, but VEGF +405 G/G genotype had lower survival with hazard ratio 1.6 [95% CI, 0.9–2.9] compared to VEGF +405 CC/GC combined genotype (p=0.04). Multivariate analysis showed that disease stage at diagnosis, and +405 G/G genotype were independent variables of adverse prognostic significance. There were no associations between the common six haplotypes identified and GC risk predisposition and survival. Conclusions: The current study suggests that VEGF polymorphisms in GC patients may have predictive and prognostic significance. No significant financial relationships to disclose.
A phase II study of ABT-869 in hepatocellular carcinoma (HCC): Interim analysis
Authors: Toh H. , Chen P. , Carr B. I. , Knox J. J. , Gill S. , Steinberg J. , Carlson D. M. , Qian J. , Qin Q. , Yong W. 
Published: August 2020

4581 Background: ABT-869 is a novel orally active, potent and selective inhibitor of the vascular endothelial growth factor and platelet derived growth factor families of receptor tyrosine kinases. Results of an interim analysis of a phase 2 trial of ABT-869 in HCC are presented. Methods: An open-label, multicenter phase II trial (M06–879) of oral ABT-869 at 0.25 mg/kg daily in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity, is ongoing. Key eligibility criteria included unresectable or metastatic HCC; up to one prior line of systemic treatment; and at least one measurable lesion by computed tomography (CT) scan. The primary endpoint was the progression free (PF) rate at 16 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed centrally and by the investigators; presented results are from central assessment. Results: 44 pts were enrolled from 09/07 to 08/08 at 6 centers internationally, with interim data available for 34 pts. There were 28 C-PA pts (median age, 63.5 y [range, 20- 81]) and 6 C-PB pts (median age, 64.5 y [range, 36–69]) and 73.5% received no prior systemic therapy. For the 19 evaluable C-PA pts included in the per-protocol interim analysis, 8 (42.1%) were progression free at 16 weeks [95% CI 20.3, 66.5]. The estimated ORR was 8.7% [95% CI, 1.1, 28] for the 23 C-PA pts and 0% for the 2 C-PB pts who had at least one post-baseline CT scan reviewed by central imaging. For all 34 pts, median TTP was 112 d [95% CI, 110, -], median PFS was 112 d [95% CI, 61, 168] and median OS was 295 d [95% CI, 182, 333]. The most common adverse events (AEs) for all pts were hypertension (41%), fatigue (47%), diarrhea (38%), rash (35%), proteinuria (24%), vomiting (24%), cough (24%) and oedema peripheral (24%). The most common grade 3/4 AEs for all pts were hypertension (20.6%) and fatigue (11.8%). Most AEs were mild/moderate and reversible with interruption/dose reductions/or discontinuation of ABT-869. Conclusions: ABT-869 appears to benefit HCC patients, with an estimated TTP of 112 days and an acceptable safety profile. Updated results from this ongoing study will be presented. [Table: see text]
Continuous sunitinib treatment in patients with unresectable hepatocellular carcinoma (HCC): A multicenter phase II trial (SAKK 77/06 and SASL 23)
Authors: Koeberle D. , Montemurro M. , Samaras P. , Majno P. , Simcock M. , Kovacs K. , Inauen R. , Hess V. , Saletti P. , Bodoky G. 
Published: August 2020

4591 Background: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenetic activity. Evidence for clinical activity in HCC was reported in 2 phase II trials [Zhu et al and Faivre et al, ASCO 2007] using either a 37.5 or a 50 mg daily dose in a 4 weeks on, 2 weeks off regimen. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients (pts) with HCC. Methods: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease and Child-Pugh A or B liver dysfunction. Pts received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression free survival at 12 weeks (PFS12) defined as ‘success’ if the patient was alive and without tumor progression assessed by 12 weeks (± 7 days) after registration. A PFS12 of ≤ 20% was considered uninteresting and promising if ≥ 40%. Using the Simon-two minimax stage design with 90% power and 5% significance the sample size was 45 pts. Secondary endpoints included safety assessments, measurement of serum cobalamin levels and tumor density. Results: From September 2007 to August 2008 45 pts, mostly male (87%), were enrolled in 10 centers. Median age was 63 years, 89% had Child-Pugh A and 47% had distant metastases. Median largest lesion diameter was 84 mm (range: 18 - 280) and 18% had prior TACE. Reasons for stopping therapy were: PD 60%, symptomatic deterioration 16%, toxicity 11%, death 2% (due to tumor), and other reasons 4%; 7% remain on therapy. PFS12 was rated as success in 15 pts (33%) (95% CI: 20%, 49%) and failure in 27 (60%); 3 were not evaluable (due to refusal). Over the whole trial period 1 CR and 40% SD as best response were achieved. Median PFS, duration of disease stabilization, TTP and OS were 2.8, 3.2, 2.8 and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent and all deaths due to the tumor. Conclusions: Continuous SU treatment with 37.5 mg/d daily is feasible and demonstrates moderate activity in pts with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design the therapy is considered promising (> 13 PFS12 successes). No significant financial relationships to disclose.
Detection of unknown primary neuroendocrine tumors (CUP-NET) using 68Ga DOTA-NOC receptor PET/CT
Authors: Hörsch D. , Prasad V. , Ambrosini V. , Hommann M. , Fanti S. , Baum R. P. 
Published: August 2020

4599 Background: This bi-centric study aimed at determining the role of receptor PET/CT using 68Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs). Methods: Overall 59 patients (M: F 33:26, age 65±9 yr) with documented NET and unknown primary, were enrolled. PET/CT was performed after injection of approximately 100 MBq (46–260 MBq) of 68Ga-DOTA-NOC. The maximum standardised uptake values (SUVmax) were calculated and compared with SUVmax in known pancreatic NET (pNET) and ileum / jejunum / duodenum (SI-NET). The results of PET/CT were also correlated with CT alone. Results: In 35/59 (59%) of patients, 68Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12/59 (20%) patients. The mean SUVmax of identified previously unknown pNET and SI-Net were 18.6 ± 9.8 (range 7.8–34.8) and 9.1± 6.0 (range 4.2–27.8), respectively. SUVmax in patients with previously known pNET and SI-NET were 26.1± 14.5 (range 8.7–42.4) and 11.3±3.7 (range 5.6- 17.9). The SUVmax of the unknown pNET and SI-NET were significantly lower (p< 0.05) as compared to the ones with known primary tumour sites. 19% of the patients had high grade, and 81% low grade NET. In 4/59 patients the primary tumour was subsequently resected (2 pancretic, one ileal and one rectal tumour). Conclusions: Our data indicate that 68Ga- DOTA-NOC PET/CT is highly superior to 111In Octreoscan (17% detection rate for CUP according to literature) and can play a major role in the management of patients with CUP-NET. No significant financial relationships to disclose.
A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer: Combined analysis with translational research
Authors: Oh D. , Lee K. , Lee K. , Sohn C. , Park Y. , Zang D. , Ryoo H. , Bang Y. 
Published: August 2020

4607 Background: To confirm the efficacy and toxicity of erlotinib (E) in combination with gemcitabine (G) and capecitabine (C) when used as a first-line therapy in patients (pts) with metastatic/recurrent pancreatic cancer Methods: Pts with advanced pancreatic adenocarcinoma, with measurable lesion were eligible for the study. Other eligibility criteria included: no previous palliative chemotherapy, Karnofsky performance status (PS)≥50, adequate organ function. Locally advanced pancreatic cancer was excluded. E was given at a dose of 100mg daily from D1 to D28. G was given at a dose of 1000mg/m2 on D1,8,15 and C was given at a dose of 1660mg/m2/d from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks. Tumor tissue and blood sample was analyzed for the translational research. Results: A total of 47 pts were enrolled between Feb 2007 and Feb 2008. (median age: 58 y, Karnofsky PS100/90/80/70/60 (6/26/9/5/1)). Forty three pts were evaluable for response. Partial responses were achieved in 14 patients, resulting in response rate of 32.6%. Twenty two pts (51.2%) had stable disease. Overall disease control rate was 83.7%. The PFS was 6.5 months (95% CI, 3.4–9.7) and the overall survival was 12.0 months (95% CI, 8.6–15.9). The Gr 3/4 hematologic toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). The major Gr 3/4 nonhematologic toxicities were: nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (0.5%). EGFR, pEGFR, TS, TP, DPD was overexpressed in 77.4%, 17.1%, 82.4%, 53.6% and 61.3% of tumor tissues respectively. EGFR amplification was not detected. Among these, the EGFR expression was significantly associated with shorter PFS and OS (p=0.029, p=0.005 respectively). K-RAS mutation was detected in 47.5%. PFS and OS were not different according to K-RAS mutation. RRM1 2455G>A, RRM1 2464G>A, CDA 79A>C, CDA 435C>T polymorphism did not influence on the PFS and OS. Conclusions: Erlotinib in combination with gemcitabine and capecitabine showed promising efficacy and good tolerability in metastatic pancreatic cancer. This efficacy was observed irrespective of K-RAS mutation, and the EGFR expression was poor prognostic factor for PFS and OS. No significant financial relationships to disclose.
Final analysis of a multicenter, randomized phase II trial comparing three different chemoradiotherapy regimens in the treatment of patients with locally advanced, nonmetastatic pancreatic cancer
Authors: Wilkowski R. , Boeck S. , Ostermaier S. , Sauer R. , Herbst M. , Fietkau R. , Flentje M. , Bruns C. J. , Rau H. G. , Heinemann V. 
Published: August 2020

4610 Background: To date, no standard treatment approach for patients (pts) with non-resectable, locally advanced pancreatic cancer (PC) is defined. Methods: Within a prospective phase II trial treatment-naive pts with locally advanced PC and adequate organ function were randomly assigned to three different CRT regimens; all pts received a conventionally fractionated radiotherapy of 50 Gy (with a daily dose of 2.0 Gy) and were randomized to either concurrent 5-FU as a 24h-infusion (350 mg/m2/d on each day of radiotherapy, RT-5FU arm), concurrent low-dose gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by a sequential chemotherapy with full- dose gemcitabine (1000 mg/m2) and cisplatin (50 mg/m2) every two weeks (RT-GC+GC arm). Treatment duration in the RT- GC+GC arm was upon disease progression or unacceptable toxicity. The primary study endpoint was the overall survival (OS) rate after 9 months (mo); secondary endpoints included response rate (WHO criteria), progression-free survival (PFS), resectability and toxicity. Results: Ninety-five patients (median age 64 years, 54% male, 50% KPS 90–100%) were recruited from 12 German centers. Seventy patients were evaluable for objective response: the intent-to-treat response rate (CR+PR) was 19% in the RT-5FU arm, 22% in the RT-GC arm and 13% in the RT-GC+GC arm, respectively. Overall, 18 pts (19%) underwent surgical resection after initial CRT (R0 in 8 pts). After a median follow-up of 8.6 mo, median PFS was estimated with 4 mo (RT-5FU), 5.6 mo (RT-GC) and 6 mo (RT- GC+GC), respectively (p=0.21). The corresponding median OS times were 9.6 mo, 9.3 mo and 7.3 mo (p=0.61). Hematological grade 3/4 toxicities were higher in the two gemcitabine/cisplatin-containing arms, but no grade 3/4 febrile neutopenia was observed. Regarding non-hematological toxicity, nausea/vomiting were more frequently in the RT-GC and RT-GC+GC arm, whereas diarrhea was more frequent in the RT-5FU arm. Conclusions: Based on these data, gemcitabine/cisplatin-based CRT does not achieve a higher clinical efficacy compared to RT-5FU, and is associated with increased hematological toxicity. [Table: see text]