bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of single agent perifosine in patients with hepatocellular carcinoma (HCC)
Authors: Campos L. T. , Nemunaitis J. , Stephenson J. , Richards D. , Barve M. , Gardner L. , Niecestro R. , Sportelli P. 
Published: August 2020

e15505 Background: Perifosine (Peri) is a novel oral alkylphospholipid with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC continues to have dismal prognosis. In a phase III randomized study, sorafenib demonstrated a 2% partial response (PR) rate with a median time to symptomatic progression of 4.1 months (mos) and radiologic progression of 5.5 mos, however patients (pts) had not received prior systemic treatment. Hence, additional therapies are needed. Peri was evaluated in a phase II multi-disease trial where 558 pts were randomized to daily vs. weekly schedules of Peri (50/100 mg daily or 900/1,200 mg weekly) with 42 of the pts having HCC. The following are the efficacy and safety results of this sub-group. Methods: Pts with advanced measurable HCC, up to 3 prior systemic treatments allowed. Normal organ / marrow function required. Primary outcome analyses included median time to progression (TTP) and disease control rate (DCR; CR+PR+SD > 12 weeks). Results: Of the 42 HCC pts treated, the median age was 71 (range 26–83), 22 were male and 48% had received > 1 prior systemic therapy. Child-Pugh status not available. As of 12/08, 32/42 pts were evaluable for efficacy (5 withdrew consent < 30 days, 4 toxicity < 30 days, 1 lost to follow up). One patient achieved a PR (3%) and 15 (47%) had stable disease > 12 weeks; overall DCR of 50%. Median TTP was 14 wks (range 2–86). As of 12/08, one patient remains active at 12 mos. The daily dose was well tolerated. The weekly dose was significantly more toxic (3 of the 4 who came off treatment < 30 days due to toxicity were on weekly). Most common grade 1/2 toxicities were GI related and fatigue. Grade 3/4 drug-related toxicities > 10% included: abdominal pain (12%), elevated liver enzymes (10%) and fatigue (10%). Conclusions: Perifosine was well tolerated at the daily dose and overall demonstrates clinical benefit in patients with advanced HCC as reflected by an encouraging TTP. A combination study with sorafenib is ongoing and future randomized studies are under consideration. [Table: see text]
A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC)
Authors: Saif M. W. , Li J. , Lamb L. , Rosenberg A. , Elligers K. , Ruta S. , Mezes M. , Grant N. , Liu S. H. , Chu E. , Cheng Y. 
Published: August 2020

e15508 Background: Gemcitabine (G) is regarded as the standard treatment for pts with APC. However, a standard second-line chemotherapy regimen has yet to be defined after G. PHY906, a 4-herb traditional Chinese medicine has a history of > 1,800 yrs of human use to treat GI symptoms including diarrhea. Preclinical studies showed that PHY906 may potentiate antitumor activity of CAP in human PANC-1 xenograft (ASCO 2007). A phase I study showed that CAP can be escalated up to 1750 mg/m2 PO BID on d1- 7 and PHY906 800mg PO BID on d1–4 q 2 wks with no DLTs (ASCO, 2008). Delivered dose-intensity of CAP was similar at 1750mg/m2 dose level as 1500mg/m2. Therefore, 1500mg/m2 of CAP and PHY906 was further tested in a phase II study as second-line treatment in pts with APC. Methods: Pts with G-refractory APC with ECOG PS <2 were treated with CAP 1500mg/m2 d1–7 with PHY906 800mg d1–4 q 2 wks. Response was assessed by CT scan according to RECIST q 6 wks and toxicity according to NCI-CTC v3.0. Primary objective is overall survival. Secondary objectives include overall RR, PFS and measurement of cytokines to assess inhibition of NF-kappa B, a possible mechanism responsible for PHY906's pharmacological activity. Results: As of January 5, 2009, 25 pts have been enrolled. Baseline characteristics include median age, 65 (range, 40–85); male/female,15/10; ECOG PS 0/1, 4/19; median cycles: 3 (r: 0.5–15). At this point 5 pts are still in active treatment. 4 pts have confirmed OS > 6 ms (1 still on study) with 2 further pts approaching 6 ms. Among evaluable pts, 1 had PR (5.3%), 11 SD (57.9%) and 7 PD (36.8%) after initial restaging scan. 36 % pts had >30% reduction in CA19–9 as biochemical response. There were 7 deaths on/within 30 days of study treatment, 6 related to PD and 1 had acute MI. G3/4 toxicities diarrhea 3/25 (12%), fatigue, 1/25 (4%), HFS 1/25 (4%) and mucositis 1/25 (4%). 1 pt was removed from study due to G3 HFS. Biomarker studies (IL4, GM-CSF, TNF-alpha, IL10, MCP-1, IL2, IL6) are ongoing. Conclusions: This is the first clinical study to evaluate a botanical formulation PHY906 with CAP in G-refractory APC pts. CAP + PHY906 regimen appears a safe and feasible salvage therapy in APC and warrants further investigation. In addition, PHY906 may have a cytoprotective antidiarrheal and anti-HFS effect, making treatment with CAP more tolerable. [Table: see text]
Prognostic significance of preoperative serum tumor markers in the patients with curatively resected advanced gastric cancers
Authors: Yoon S. , Yoo C. , Park I. , Chang H. , Kim T. , Lee J. , Yook J. , Oh S. , Kim B. , Kang Y. 
Published: August 2020

e15515 Background: We evaluated the prognostic significance of preoperative tumor markers, carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA19–9), and carbohydrate antigen 72–4 (CA72–4), in the patients with curatively resected advanced gastric cancers (AGC). Methods: Preoperative serum tumor markers were available for 667 patients who had been enrolled in a phase III trial of adjuvant chemotherapy (AMC0201). We compared the relapse free survival (RFS) and overall survival (OS) according to patient's pre-treatment clinical characteristics and serum tumor markers by using log rank test and Cox proportional hazard model. Results: Of total 667 patients, 3 year RFS rate and OS rate were 67.4% and 75.0%, respectively. Postoperative pathologic stage was II in 353 (52.9%), IIIA in 202 (30.3%), IIIB in 61 (9.1%), and IV (M0) in 51 (7.6%). CEA, CA19–9, CA72–4 were elevated pre-operatively in 64 of 665 patients (9.6%), 75 of 664 patients (11.3%), and 121 of 639 patients (18.9%), respectively. After the median follow-up of 38.4 months, 209 patients (31.3%) had recurrence, and 164 patients (24.6%) died. In the univariate analysis, location of tumor, type of surgery, Borrmann type, TNM stage, the elevation of CEA and CA72–4 level were significant prognostic factors for RFS and OS. In the multivariate analysis, serum CA72–4 was independent significant prognostic factor for RFS and OS as well as tumor location, Borrmann type, and stage Conclusions: Pre-operative serum CEA and CA72–4 levels were independent prognostic factors as well as clinical characteristics of pathologic stage, tumor location and Borrmann type in patients with curatively resected AGC. No significant financial relationships to disclose.
Combined chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 for malignant ascites due to advanced gastric cancer with peritoneal dissemination
Authors: Kitayama J. , Ishigami H. , Kaisaki S. , Hidemura A. , Kato M. , Nagawa H. 
Published: August 2020

e15524 Background: Malignant ascites caused by peritoneal metastasis the most life-threatening mode of metastasis and recurrence and seriously impair the quality of life in patients with gastric cancer. However, none of the treatment protocols have proved satisfactory clinical outcome. Methods: Twenty one patients with malignant ascites due to the peritoneal dissemination of gastric cancer were enrolled. Intraperitoneal catheter with infusing port was placed subcutaneously in all patients, and Paclitaxel was administered intraperitoneally at 20 mg/m2, together with intravenously at 50 mg/m2, on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. The change of the ascetic volume was prospectively investigated as the primary endopoint of the response rate. The volume of malignant ascites was objectively measured with the calculation of the consecutive computed tomography (CT) images using NIH image J software. Peritoneal cytology and mRNA of CEA in acitic fluid were also evaluated in 17 and 16 cases, respectively. Results: The volume of malignant ascites before the treatment was more than 500ml in 8 patients and less than 300ml in 13 patients. The average course of the treatment was 9 (2–19). The ascetic volume was markedly (more than 33%) reduced in 8 patients and totally disappeared in 5 cases with CT image, and thus the response rate was 62%. Malignant cells in peritoneal cytology disappeared in 13 cases while CEA mRNA became negative only in 2 cases. The one year overall survival was 71% in all patients and 85% in patients with reduced ascites. Conclusions: Combined chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 was a useful protocol for malignant ascites caused by peritoneal dissemination of gastric cancer. No significant financial relationships to disclose.
Analysis of signal pathway activation in hepatocellular carcinoma: Association with clinical outcomes to sorafenib in Chinese patients
Authors: Ji Y. , Fan J. , Zhang L. , Tan Y. , Zhou J. , Zeng H. , Ren Z. , Xu J. 
Published: August 2020

e15529 Background: The pathogenesis of hepatocellular carcinoma invovles multi-stage development of molecular aberrations affecting signaling pathways that regulate cancer growth and progression. Treatment strategies have focused on inhibition of the Ras effector pathway with inhibitors of Raf, such as sorafenib in HCC. Greater understanding of the cellular response to sorafenib is needed to tailor targeted therapy for individual patients and identify those more likely to benefit. Methods: We performed immunohistochemistry on a tissue microarray of tumor and adjacent liver tissue from 40 HBV-infected HCC patients who were treated with sorafenib, and 20 normal liver. We compared the levels of 8 signaling proteins including growth factor receptors (PDGFRa, VEGFR1, VEGFR2, VEGFR3, c-kit, c-met, IGF-R, EGFR), tumor suppressors (PTEN) and their downstream phosphorylated (p-) signal transducers (p-RAF, p-MEK1/2, p-ERK1/2; PI3K, p-AKT, NFkB, axin, β-catenin,p-GSK3β, p-mTOR, p-S6, p-70S6K, p-JNK, p-SRC, p-STAT3, c-fos, c-jun) in cancer cells and endothelial cells of HCC to those in non-neoplastic liver. Results: The overall profiles of signalling protein expression levels, activation states and subcellular distribution in HCC cells and endothelial cells were distinguishable from non-neoplastic hepatocytes. The ERK pathway activation was correlated with low level of nuclear β-cat and high level of p-mTOR (p<0.05). Long survival (>6m) patients were characterized by high level of nuclear pERK and low level of p-AKT, p-GSK3β (p<0.05) in tumor cells. The high microvessel density and the presence of micrometastases correlated with high level of VEGFR, p-ERK and p-SRC in endothelial cells. Conclusions: Sorafenib may affect signalling through the Ras/Raf/MAPK/ERK pathway. HBV-related HCC patients with. overactivation of signal transduction cascade MAPK/ERK and PI3K/AKT pathways in tumor cells and/or endothelial cells may benefit from the targeted treatment. No significant financial relationships to disclose.
Application of a time-varying covariate model to the analysis of CA 19–9 as a biomarker for time-to-progression (TTP) and overall survival (OS) in patients with advanced pancreatic cancer
Authors: Boeck S. , Laubender R. P. , Haas M. , Klose C. , Kullmann F. , Buchner H. , Bruns C. J. , Stieber P. , Mansmann U. , Heinemann V. 
Published: August 2020

e15545 Background: It remains unclear whether baseline CA 19–9 or CA 19–9 kinetics during chemotherapy may serve as predictive biomarker in patients (pts) with pancreatic cancer (PC). Methods: Main inclusion criteria for this retrospective multicenter analysis: histologically confirmed diagnosis of PC, treatment with first-line therapy, pre-treatment CA 19–9 level of > 5.2 U/ml. Analysis of CA 19–9 was exclusively performed using the Elecsys® assay (Roche Diagnostics). The effect of the pre- treatment CA 19–9 level on TTP and OS was modelled by Cox proportional hazards regression. The effect of CA 19–9 kinetics was also modelled by Cox proportional hazards regression where CA 19–9 was treated as time-varying covariate. When modelling CA 19–9 we developed univariate and multivariate Cox models where we selected additional predictors (e.g. performance status) using backward elimination performing likelihood ratio tests on a significance level of 0.05. Results: One-hundred and fifteen pts from 5 German centers were included. Median age was 63 years, 12% had locally advanced and 88% metastatic disease; 73 % of the pts were treated within prospective clinical trials. Median baseline CA 19–9 was 1059 U/ml (range 9.5–100000), median pre- treatment bilirubin 0.6 mg/dl. The median TTP in the study population was 4.4 months, median OS 9.4 months. Univariate analysis showed that the pre-treatment CA 19–9 level (as continuous variable, log [CA 19–9]) was significantly associated with TTP (HR 1.24, 95% CI 1.12–1.37, p<0.001) and OS (HR 1.16, 95% CI 1.06–1.28, p=0.002). These associations remained significant also within a multivariate analysis. For CA 19–9 kinetics during chemotherapy, data from 69 pts (TTP) and 84 pts (OS) were available, respectively; log [CA 19–9] kinetics were found to be a significant predictor for TTP in univariate (HR 1.44, 95% CI 1.25–1.67, p<0.001) and multivariate (HR 1.39, 95% CI 1.19–1.62, p<0.001) analyses, and also for OS (univariate: HR 1.34, 95% CI 1.20–1.49, p<0.001; multivariate: HR 1.39, 95% CI 1.23–1.57, p<0.001). Conclusions: According to this new statistical model, CA 19–9 may serve as a useful predictive biomarker in advanced PC. [Table: see text]
Impact of lymph node metastases on outcome following treatment with sorafenib in patients with hepatocellular carcinoma (HCC): Subset analysis from the phase III SHARP trial
Authors: Raoul J. , Craxi A. , Porta C. , Lentini G. , Nadel A. , Voliotis D. , Bruix J. , Llovet J. M. 
Published: August 2020

e15547 Background: Results from the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, a multinational, randomized, placebo-controlled, phase III trial, demonstrated that sorafenib is effective and safe for patients with advanced HCC (Llovet et al, N Engl J Med, 2008). As lymph nodes are among the most common sites of metastasis in patients with HCC, we performed subset analyses to evaluate the efficacy and safety of sorafenib in patients with or without lymph node metastases at baseline. Methods: Patients (N=602) with advanced, unresectable, measurable HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy for HCC were randomized 1:1 to receive either sorafenib 400 mg BID or placebo. End points included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 d from first demonstration of response), time to progression (TTP), and safety. Results: Median TTP, OS, and DCR by subset are shown in the table. The incidence of grade 3/4 drug-related adverse events across subgroups was consistent with that reported for the overall population. The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib prolonged OS and TTP in patients with advanced HCC, whether or not lymph node metastases were present at baseline. The safety profile of sorafenib in patients with lymph node metastases was comparable with that for the overall study population. [Table: see text] [Table: see text]
Phase II trial of neoadjuvant fixed dose rate (FDR) gemcitabine with capecitabine (GX) combination chemotherapy in locally advanced pancreatic adenocarcinoma (LAPA)
Authors: Lee J. , Lee S. , Kim T. , Lee J. , Park D. , Seo D. , Lee S. , Kim M. , Han D. , Kim S. 
Published: August 2020

e15553 Background: To determine the efficacy and safety of fixed dose rate (FDR) gemcitabine and capecitaibne (GX) combination chemotherapy for locally advanced pancreatic adenocarcinoma Methods: Patients with histologically confirmed LAPA were eligible for this prospective phase II trial. Dynamic pancreas/pelvic CT, MRI and FDG-PET were undertaken to assess the resectability. EUS was also performed as needed basis. ‘Borderline resectable (BR)’ and ‘unresectable (UR)’ criteria developed by our pancreatico-biliary multidisciplinary management team (PBMMT) and NCCN criteria were used. After confirmation of resectability, patients received 3 cycles of FDR gemcitabine 1,250 mg/m2 on D1 and D8 and capecitabine 950 mg/m2 from D1-D14 every 3 weeks. Thereafter, staging was repeated and patients underwent surgery if the disease was not unresectable. For patients with R0 resection, additional 6 cycles of GX were administered. For patients with R1 resection, chemoradiotherapy (CRT) (54 Gy over 5 weeks with concurrent 5-FU and leucovorin or capecitabine) followed by FDR-GX was administered. Patients with stable or better response to chemotherapy but assessed unresectable at reassessment received additional chemotherapy up to 9 cycles followed by CRT. Results: Between August 2006 and July 2008, 38 eligible patients (14 with BR and 24 with UR based on NCCN criteria; 29 with BR and 9 with UR based on our PBMMT criteria) entered on this study. The median age was 61 yo (42–76) and 71% had cT4 disease. The response to neoadjuvant chemotherapy was PR in 6 (16%), SD in 26 (68%) and PD in 3 (8%). Metabolic response was achieved in 20 patients (53%) with 2 metabolic CR out of 31 evaluable patients. Grade 3 or worse adverse effects were mainly HFS (n=5) and gastrointestinal (n=3) with no grade 4 in severity. Surgery was performed in 9 patients (24.0%, R0=8, R1=1, 6 in NCCN-BR and 3 in NCCN-UR, 9 in PBMMT-BR) and five patients refused surgery although their diseases seemed not to be unresectable. The median PFS was 9.4 months (95% CI, 8.3–10.4) and estimated median OS was 13.5 months (95% CI, 12.4- 14.5). Conclusions: FDR-GX was effective as neoadjuvnat chemotherapy in LAPA with favorable toxicity profile. No significant financial relationships to disclose.
Definitive chemoradiation therapy with capecitabine in locally advanced pancreatic cancer
Authors: Yi S. , Kim H. S. , Lee J. , Park S. , Park Y. , Lim H. , Kang W. , Park H. , Lim D. , Park J. O. 
Published: August 2020

e15558 Background: We evaluated safety and efficacy of concurrent chemoradiotherapy (CCRT) with capecitabine in patients with locally advanced pancreatic cancer (LAPC). We also tried to devise a prognostic model for LAPC undergoing definitive CCRT. Methods: Between January 2004 and January 2008, 39 patients with LAPC treated with capecitabine CCRT were reviewed. Capecitabine was administered at 850 mg/m2 bid every day for 5 weeks. Radiotherapy was given 5 days per week, at 1.8 Gy fractions, over the 5 weeks. Results: Thirty seven (94.8%) patients completed CCRT, and 2 patients removed during the treatment for toxicity issues. Of the 36 evaluable patients, 15 (41.7 %) patients achieved partial response, and 13 (36.1 %) had a stable disease with 77.8% of disease control rate. Among the 28 patients who had achieved disease control after CCRT, 8 patients (21.6 %) received gemcitabine-based post-CCRT chemotherapy without dose reduction or delay. With median 1.8 years of follow- up, the overall survival was 14.3 months (95% confidence interval [CI]; 10.6–17.9 months). Median progression free survival was 11.1 (95% CI 7.2–15.1) for all patients, and 7.9 months (95% CI 6.6–9.2) for those not received post-CCRT chemotherapy. No patient had grade 4 hematologic or non-hematologic toxicity. Eight patients (21.6%) had severe grade 3 toxicities, 7 (18.9%) with gastrointestinal toxicity and 1 (2.7%) with hematologic toxicity. Prognostic factors for survival were serum albumin (P=0.014; relative risk [RR], 3.4; 95% CI, 1.4, 8.6), and adjuvant gemcitabine treatment (P = 0.005; RR, 3.5; 95% CI, 1.2, 10.6). The prognostic grouping resulted in three groups with significantly different prognosis: group 1 (0 adverse factor; n=8; 1-year survival, 87.5%), group 2 (1 adverse factor; n=23; 1-year survival, 52.9%) and group 3 (2 adverse factors; n=8; 1-year survival, 25.0%). Conclusions: Combined therapy with capecitabine CCRT was well tolerated. Capecitabine seems to be a promising regimen in the treatment of LAPC, in terms of response, survival, and tolerable adverse effects. No significant financial relationships to disclose.
Use of PET SUV for primary tumor to predict outcome in locally advanced esophageal cancer treated with trimodality therapy
Authors: Videtic G. M. , Macley H. M. , Reddy C. , Adelstein D. J. , Rice T. W. , Saxton J. P. , Venigalla N. , Srinivas S. 
Published: August 2020

e15559 Background: To assess the value of the primary tumor's SUVmax (PT-SUVmax) from the staging FDG-PET as a predictor of clinical and pathologic outcomes in patients undergoing trimodality therapy for locally advanced esophageal cancer. Methods: A retrospective chart review was conducted on patients with T3/4 and/or node positive esophageal carcinoma treated at the Cleveland Clinic between 7/1/03 and 5/31/06. All patients were managed with an institutional regimen consisting of preoperative radiotherapy [30 Gy @ 1.5 Gy twice daily over two weeks] with concurrent cisplatin and 5-fluorouracil during the first week. Following resection, an identical postoperative course of concurrent chemoradiotherapy (CRT) was delivered. Pretreatment patient and tumor characteristics including PT-SUVmax were analyzed with respect to response and survival. Results: 141 patients completed preoperative CRT: 125 (88.7%) were male, median age was 60 years, 73.8% had adenocarcinoma, 79.4% had N1 disease, 81.6% underwent surgery and 63.8% completed the full regimen. Median follow-up was 17.2 months [range 0.7–75.1]. Median PT-SUVmax was 9.43 [range 0 to 47.7]. Increasing clinical stage was associated with increasing PT-SUVmaxs: for cT2 vs. cT3 and cN0 vs. cN1, PT-SUVmax cutoffs were 8 (p=0.03) and 11 (p=0.02), respectively. Median (MST) and 5-year overall survivals were 20.7 months and 27.4%, respectively. A PT-SUVmax of < vs. > 7 was a significant predictor for T downstaging (p=0.0502) and N downstaging (p=0.0467). A PT-SUVmax cutoff of 7.6 was associated with a significant difference in MST, at 29.1 and 13.0 months for PT-SUVmax< 7.6 and >7.6, respectively (p=0.0158, HR=1.82, 95%CI=1.19–2.94). On multivariate analysis, PT-SUVmax was the only significant factor associated with survival (p=0.0.314, HR=1.71, 95%CI=1.05–2.79). Conclusions: The pretreatment SUVmax of a primary esophageal cancer appears to correlate with clinical stage, pathologic response to therapy and survival. This finding could play a role in the design of clinical trials and in adapting treatment strategies. No significant financial relationships to disclose.