bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combination phase I study of biweekly docetaxel and 5’-DFUR in patients with unresectable or recurrent gastric cancer
Authors: Yoshino S. , Oka M. , Hazama S. , Shimizu R. , Yamamoto T. 
Published: March 2020

14115 Background: Docetaxel (DOC) and 5’-DFUR (an intermetamolite of capecitabine) have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between DOC and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase. The objectives of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the recommended dose (RD) of the combination therapy of biweekly DOC and 5’-DFUR. The DLT was set in low grade to treat the patients in the outpatient clinic. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer, no requirement of prior chemotherapy, a performance status of 0–2, adequate organ function and written informed consent. DOC was administered by 1-hour intravenous infusion (level 1, 2, 3, 4: 30, 35, 40, 45 mg/m2) biweekly for 4 weeks. 5’-DFUR was administered orally at a fixed dose of 600mg/body everyday. Toxicity and efficacy were evaluated during the 2 cycles for 8 weeks. Three or 6 patients were enrolled at each dose level. Administration of DOC was skipped in the event of grade 2 hematologic toxicity. DLT was defined as grade 3 hematologic toxicity, grade 2 non-hematologic toxicity. The MTD was defined as the dose level at which at least two of three patients or three of six patients presented with DLT. Results: Twelve patients with a median age of 58 years (range, 29 to 75) were enrolled in this study. Five patients have received prior chemotherapy. Eight patients were unresectable and 4 had recurrent tumors. At level 1 (n=3), 2 (n=3), 3 (n=3), no patients developed DLT. Two patients developed DLT at level 4 (n=3). All DLT was neutropenia. Only 1 developed grade 4 neutropenia at level 4. Non-hematological toxicity was uncommon. Level 4 was determined as the MTD. Of 8 evaluable patients, responses included 4 PR, 3 SD and 1 PD for an overall response rate of 50%. Conclusions: The MTD of DOC in this combination is 45 mg/m2 and the RD is 40 mg/m2. This regimen is well-tolerated with high response rate in outpatient setting. A phase II study is necessary to evaluate the response of this regimen. No significant financial relationships to disclose.
Evaluation of nitinol stent placement complications for palliation of malignant dysphagia
Authors: Alach E. , Troncoso E. , Barbero A. , Mainella A. , Lavezzaro M. , Zapata G. , Bonicatto S. 
Published: March 2020

14120 Background: Over 50% of patients (pts) with obstructive carcinoma are inoperable at the time of the diagnosis and only 18% of them survive beyond a year. Palliative treatment must be quickly effective, safe, well tolerated and focused to relieve symptoms, improving the nutritional state and quality of life. The objective of the study was to investigate the clinical effectiveness and complications of palliative treatment with esophageal stent placement. Methods: Descriptive and prospective study about functionality of nitinol autoexpandible stent was carried out. Evaluable pts included those with confirmed histological diagnosis of inoperable or unresectable esophageal cancer, with some clinical contraindication due to risk or personal rejection. An immediate post placement follow-up was performed after 24hours, 7 and 30 days, to evaluate the stent proper location, its permeability as well as its degree of expansion, presence of epigastric or precordial pain, reflux and degree of dysphagia. Results: From August/02 to September/05 stent was placed in 20 people, 9 women and 11 men, mean age 67.8 (range: 42–85). The autoexpandible stent placement was achieved in 100% of pts (3 = gastric carcinoma and 17 = esophagus carcinoma). Histological diagnosis was epidermoid (11 pts) and adenocarcinoma (9 pts). Inoperable malignant stricture was as follows: lower third: 11 pts (55%), middle third: 9 pts (45%). A second stent was required in 2 pts. Median time of hospitalization was 48 hours.Immediate complications appeared in 12 pts: pain 3 (15%), vomiting 3 (15%), pneumonia 2 (10%), cough 1 (5%), pyrosis 1 (5%). After 24 hour control: pain 2(10%), respiratory complications 2 (10%). The delayed ones were as follows: level 4 dysphagia 2 (10%), pain 8 (40%), reflux 5 (25%). No mortality related to stent placement was observed. Dysphagia was perceptibly reduced, from 3.0 to 1, (p < 0,005). Conclusion: The nitinol stent is easy to place, it provides effective palliation of malignant esophageal obstruction with short hospitalization time and low risk of serious complications. No significant financial relationships to disclose.
Lymphadenectomy in carcinoma stomach: Experience from a regional cancer centre
Authors: Mahajan V. 
Published: March 2020

14121 Background: Carcinoma stomach is the most common cancer in males in chennai city. Lot of controversy exists regarding the need for extended lymphadenectomy because of the morbidity and mortality associated. Methods: A retrospective analysis was done to assess the benefit of extended lymphadenectomy. The records of all the patients operated at Cancer Institute from 1991 to 2004 were analysed. Out of 5050 cases of carcinoma stomach seen, only 570 cases were taken up for some form of treatment. 400 cases underwent resection, of which 366 patients records were retreived from the tumor registry for analysis. Followup ranged from 1 year to 10 years. Results: Male to female ratio was 3:1, most patients were in 40 - 60 year age group (60%). 60% patients had antral tumors and the rest were evenly distributed. 79 patients (21%) underwent conventional gastrectomy (D1), 243 patients (66%) underwent extended lymphadenectomy and 44 patients (12%)underwent palliative gastrectomy. 280 patients underwent subtotal gastrectomy, 54 patients total gastrectomy, 28 esophago gastrectomy and 5 had transhiatal esophagectomies. Stage wise distribution was IA 4.9%, IB 9.8%, II 21%, IIIA 29.4%, IIIB 12.8%, IV 22.1%. The total number of nodes dissected in the Extended nodal dissection group was less than or equal to 15 in 12% patients, 15 to 30 nodes in 48% patients and >30 nodes in 40% patients. 72% patients had node positive disease. Overall Survival at 5years was 38.9% for all the cases. 5year ovarall survival for conventional gastrectomy group was 37% and was 48% for the extended lymphadenectomy group which was statistically significant(p =0.06) .On substratification for T status and stage, the difference in survival between conventional and extended lymphadenectomy arms was not found to be significant.However,there was a trend towards improved survival in the lymphadenectomy arm.There were 7 post operative deaths in the lymphadenectomy arm,5 of which were in the first year of starting extended lymphadenectomies, which points to the learning curve for these procedures. Conclusions: Larger trials may be required to prove the advantage of extended lymphadenectomies in Gastric cancer. In addition neoadjuvant chemotherapy and Intraoperative radiotherapy may need to be studied to improve survival in gastric cancer. No significant financial relationships to disclose.
Analysis of preclinical and clinical data on the role of hyperthermia with gemcitabine and carboplatin on pancreatic adenocarcinoma
Authors: Peters S. O. , Stoltz A. S. , Bakshandeh A. , Vollmert M. , Wagner T. 
Published: March 2020

14123 Background: Preclinical data show synergism of whole body hyperthermia (HT) of 41.8°C with gemcitabine (G) and carboplatin (CP) in lung head and neck tumor cell lines. Advanced pancreatic adenocarcinoma is an aggressive disease and is associated with high morbidity and a median survival of 8 to 12 months. The role of whole body HT with G and CP in the treatment of pancreatic cancer is unknown. Methods: We first show preclinical data to study the effects of combining HT of 37°, 39°, 41.8 and 43°C for 1 h with G and CP on the human pancreas carcinoma cell line DAN-G. We assessed proliferation ratios using crystal-violett assays and cell cycles by flow cytometry. We secondly analyzed the clinical outcome of 13 pts that received whole body HT of 41.8°C with G and CP for advanced pancreatic cancer on a compassionate-use basis at our institution between 2000 to 2004 was assessed for toxicity, response and overall survival. Results: Preclinical studies showed no effects of HT of 37, 39 and 41.8°C on DAN-G cell proliferation and cell cycle behaviour when used alone without cytostatic drugs. At 43°C cells decompose (in all experiments). Additional G and/or CP at concentrations of IC50 to HT of 37, 39, 41, 8°C did not alter the effects of the drugs alone. Cell cycle anaylsis showed that an increment of temperatures did not effect cycle phases. Analysis of the clinical data of patients whole body HT with G and CP showed partial remissions in 3 pts (23%) and no change situations in 5 pts (38%). Of 13 pts received only 2 cycles because of disease progression (n = 5) or because they refused to further treatment due to minor toxicities. 4 pts received all 4 therapy cycles initially planned. Overall survival was 11.4 months, one year survival for all patients was 38%. Generally the treatment was well tolerated. Grade 3–4 toxicities were thrombocytopenia in one patient and therapy induced anemia and neutropenia in another patient occurring after the forth cycle of treatment. Conclusions: Preclinical and clinical data show that HT plus G and CP is of no benefit in the treatment of pancreatic cancer. No significant financial relationships to disclose.
An open-label phase II study evaluating the safety and efficacy of PTK787 in patients with progressive metastatic neuroendocrine cancer
Authors: Anthony L. B. , Cronin M. , O’Dorisio T. , O’Dorisio S. 
Published: March 2020

14124 Background: PTK787, an aminophthalazine, is an orally active angiogenesis inhibitor blocking all known vascular endothelial growth factor receptors (VEGFR)- and platelet-derived growth factor receptor (PDGFR)-tyrosine kinases . The majority of metastatic neuroendocrine malignancies express VEGF and PDGF receptors. Since both growth factors have been implicated in tumor-induced angiogenesis, PTK787 offers a novel approach for inhibiting tumor growth. Methods: In a phase II trial, we investigated the safety and antitumor activity of PTK787 in patients who had biopsy-proven metastatic neuroendocrine cancer, such as carcinoid, and had shown evidence of progression on somatosatin analog therapy. Eligible patients had measurable lesions other than bone, a Karnofsky performance status >60 and normal hematologic, renal and hepatic functions. Patients on octreotide therapy were required to be on a stable dose not exceeding 30 mg monthly of the LAR formulation. Initial dosing of PTK787 was 1,250 mg daily. Results: Six patients (4 males) were enrolled between 5/20/05 to 8/09/05. Median age was 61 years (range, 48 to 65). There was 1 withdrawal of consent. The remaining 5 patients continue on treatment as of January 2006. One patient required a 10 day discontinuation for rising SGOT/SGPT and alkaline phosphatase. Resumption of PTK787 at 1,000 mg daily was well tolerated in this patient. Radiographically and scintigraphically, all 5 patients have demonstrated stable disease by CT and OctreoScan, respectively. Recruitment to this trial continues. Conclusions: PTK787 is generally well tolerated in patients with metastatic neuroendocrine cancer and may be effective in controlling somatostatin analog resistant disease though partial radiographic responses have not been observed. No significant financial relationships to disclose.
Laboratory based low dose combination chemotherapy + bevacizumab for recurrent refractory and unresectable gastric cancer
Authors: Bruckner H. W. , Hrehorovich V. R. , Degregorio P. 
Published: March 2020

14133 Twenty consecutive prospectively registered patients with refractory or Stage IV gastric cancer were treated with GFLIP (Bruckner el al ASCO 2002;2005). The last 10 upon relapse were treated with GFL[OX]T and Bevacizumab, substituting oxaliplatin (OX) 30→40 mg/M2, taxotere (T) 30→40 mg/M2 for cisplatin in the q2wk schedule. One or both regimens produced; objective responses for 15 patients including 5 complete (radiologic, tumor markers, PET responses) and 2 surgical downstaging resulting in resection or successful completion surgery; 3 patients had stable disease greater than 4 months with subjective benefit, gemcitabine was given at 400→500 mg/M2 as tolerated (→), 2 failed both regimens. One-year actuarial survival was 75%, two-year survival was 25%. All 20 lived more than six months. The level of activity, multiple crossover responses, responses with both regimens, a number of long remissions (long survival after 5FU cisplatin and GFLIP failed) and clinical downstaging allowing further surgery identify both regimens either individually or in sequence as deserving systematic investigation. The utility of low doses (responses), unusual clinical benefits, quality of life and safety offer possible advantages compared to standard dose regimens.This strategy appears to reduce and delay the limiting toxicity of the irinotecan (I) 80 mg/M2, cisplatin (P) 40 mg/M2 OX/T which are conventionally treatment limiting drugs. The regimens were designed based on laboratory evidence of low dose drug interaction including reversal of resistance to conventional drugs (applicable to both pancreatic and gastric cancer (Janat et al, Amer Asso Cancer Res 1999). After clinical demonstrations of high response rates and reversal of resistance against refractory pancreatic cancer (Bruckner et al, AntiCancer Res and ASCO 2005). The regimens were offered to patients with recurrent previously treated and refractory gastric cancer and then based on initial exceptional responses to high risk patients with poor prognosis due to clinical complications of their gastric cancer. No significant financial relationships to disclose.
Efficacy of oxaliplatin and 5-fluorouracil in advanced hepatocarcinoma
Authors: Tahri A. , Quang T. , Dien V. , Nam L. , Biset J. , Guillon J. , Tahiri F. 
Published: March 2020

14143 Background: Hepatocarcinoma (HCC) is one of the commonest malignancies worldwide. Advanced HCC represents one of the most frustrating issue, when further loco-regional therapy is not available for tumor extension, major blood vessel thrombosis or poor liver function. Systemic and palliative treatments are still discouraging. Oxaliplatin (OXA) and 5-Fluorouracil (5-FU) combination has shown in vitro and in vivo activity, moreover prolonged infusion of 5-FU could be useful in preventing DNA repair from OXA. This combination can be an interesting treatment for patients affected by advanced HCC as previously reported (Bearz A. et al, Proc ASCO # 2343, 2001. Frustaci S. et al, Proc ASCO # 1346, 2003). The goal of this work is to evaluate the feasibility, toxicity and response rate of this protocol. Methods: Inclusion criteria were inoperable or metastatic HCC, measurable parameters, PS < 2, creatinine < 1,5 mg/dL, total bilirubin < 4 mg/dL, any previous treatment. Chemotherapy consisted of: OXA 100 mg/m2 in 2 hrs perfusion; 5-FU 200 mg/m2/day as a continuous infusion for 14 days. Cycles were repeated every 2 weeks until progression or grade 3–4 toxicities. Results: From October 2002 to November 2004, 8 patients (pts) (6M, 2F) were treated. Median age was 53 years, 2 pts were affected by hepatitis C (HCV), 3 by hepatitis B (HBV), 2 by both HCV and HBV and 1 by alcoholic cirrhosis. Stage: IVA in 4 pts, IVB in 4. 5 pts were totally untreated and 3 had chemoembolization. Median number of administered cycles for patient was 6 (3–11). We observed haematological toxicity grade 2 in 2 cases, diarrhoea, peripheral neuropathy and nausea grade 2 in 1 case respectively. Partial response was obtained in 4 pts, stable disease in 2, progression in 1, 1 patient is lost to follow-up. Up to now, median duration of response is 6 months. Conclusions: The regimen showed to be feasible tolerable and with interesting response rate for HCC patients not suitable for other therapeutical options. The results are encouraging and warrant a further phase III study. No significant financial relationships to disclose.
Our experience of low-dose consecutive CDDP and intermittent S-1 (LP/IS) therapy for advanced gastric cancer
Authors: Kobayashi K. , Enjoji A. , Nagata Y. , Tajima Y. , Kanematsu T. 
Published: March 2020

14145 Background: 5-FU and CDDP combination chemotherapy (FP) has been widely used as standard therapy for advanced gastric cancer (AGC), and in Japan FP therapy was modified into [5-FU (CVI) and low-dose consecutive CDDP (LC-P)](LFP) Therapy from 1990. LFP therapy has been widely used for the treatment of AGC, because of low toxicity and high response rate. We observed that CDDP inhibited metionine transport into tumor cells, both in vitro and in vivo, with synergistic interaction by CDDP functioning as a modulator of 5-FU. However LFP Therapy needs 24-hour continuous infusion of 5-FU, the applicants for LFP must be hospitalized. Therefore we used S-1, novel oral fluoropyrimidine as effector of 5-FU, and combined LC-P aiming the same synergy as LFP therapy. In addition, utilizing the difference in cell cycle between normal cells and tumor cells, we applied intermittent administration of S-1, which leads lower toxicity than conventional LFP therapy. We tried this LC-P and intermittent S-1 (LP/IS) Therapy for AGC, examining whether LP/IS was possible as outpatient-basis. Methods: Patients with AGC received LP/IS therapy. S-1 (80 mg/m2/day) was administered per orally and CDDP (10 mg/body/day) was infused for half an hour. The administration schedule consisted of S-1 for 1,3,5 days intermittently and CDDP for 2,5 days twice a week for each four weeks. RESIST criteria and NCI-CTC (ver.3) were used to assess LP/IS. Results: Between July and November 2005, four patients (A/B/C/D) were entered into this trial. Information is available for all patients. Characteristics were: age (A/B/C/D=75/59/65/54): sex (A/B/C=M, D=F): disease status (A/B= locally advanced, C/D= postoperative recurrence). S-1 and CDDP were administered to 97.9% and 84.4% of planned dose, respectively. As for toxicity, only grade 2 taste disturbance and anorexia occurred in two patients. All the patients had one course LP/IS and are evaluable for anti-tumor effects; primary (A/B=NC/NC), metastatic (A/B/C/D=NC/NC/NC/PD), respectively. A and B could undergo total gastrectomy. TTF was (A/B/C/D=42/35/55/29 days), and survival time was (A/B/C/D=164/94/104/71 days, C: dead). Conclusions: Because of low toxicity and high feasibility, LP/IS therapy is appropriate for out-patient basis chemotherapy for AGC. No significant financial relationships to disclose.
Capecitabine therapy in advanced gall bladder cancer: A phase II study
Authors: Chowdhury Q. , Reza S. , Hai M. , Shahid S. 
Published: March 2020

14153 Background: Thymidine phosphorylase (TP) activity is found at higher levels in gall bladder cancer (GBC) tissues than in adjacent healthy tissues. GBC is relatively sensitive to 5-FU. TP activated capecitabine (CAP) mimics the continuous infusion of 5-FU. In view of drug potentiality this present study was initiated. Our aim was to evaluate the therapeutic efficacy and safety of CAP in previously untreated GBC patients (Pts). Methods: It was an open-labelled, single-centred, non-randomised and prospective study. Outcome measures were response rate and type of response for efficacy measurement and safety was measured by adverse events & laboratory blood values (LBV). All LBV were within reference range at baseline. The patients had no prior chemo/ radio therapy or a family history of malignancy; adenocarcinoma (stage III–IV); age 40–70 yrs; male/female: 16/ 30; KPS ≥ 70%. 46 pts were treated with 306 cycles (min 3–max 12) of CAP at a dose of 2500 mg/day in two divided doses from day 1–14 followed by 1-week rest. Results: Median age was 50 yrs. Hand foot syndrome occurred in 17.39% pts, diarrhoea (grade 3 & 4) 21.75% and both 15.21%, all toxicities were manageable. Mean LBV before and after CAP therapy were hemoglobin: 11.38–0.35 g/dl (95% CI, 10.66–2.10); total count of WBC: 9,260–580/mm3 (95% CI, 8,680–9,840); platelet count: 251,000–2,000/mm3 (95% CI, 227,000–275,000) and serum bilirubin: 1.17–0.33 mg/dl (95% CI, 0.5–1.84). The LBV between baseline and after CAP therapy were not statistically significant. Partial response was found in 12 pts (26.08%), stable disease in 26 pts (56.21%), and progressive disease in 8 pts (17.39%). Mean KPS value after therapy was 76% (95% CI, 69–84). Conclusion: This clinical experience indicates that CAP is a convenient choice in phase II chemo naïve GBC pts not adversely affecting haematological values. No significant financial relationships to disclose.
Expression of caveolin-1 in renal neoplasms
Authors: Zhou M. , Tamaskar I. , Sercia L. , Rini B. I. , Bukowski R. M. 
Published: March 2020

14509 Background: Caveolin-1 is the major structural and functional component of caveolae, which are specialized lipid raft microdomains on cell membrane important for signaling pathways related to cell adhesion, growth and survival. Studies have shown that clear cell renal cell carcinoma (CCRCC) expressed caveolin-1 and that the over-expression correlated with adverse pathological findings and poor outcomes. The expression of caveolin-1 in other types of renal tumors has not been studied. Methods: A tissue microarray (TMA) was constructed from 60 normal kidneys, 22 CCRCC, 20 papillary renal cell carcinomas (PRCC), 16 chromophobe renal cell carcinomas (ChRCC), and 19 oncocytomas (ONC). The TMA was immunostained for caveolin-1 protein. Membranous caveolin-1 expression was scored using the internal vascular endothelial cells as positive control. Results: Membranous caveolin-1 expression was detected in 19/22 (86.4%) CCRCC, in 1/20 (5%) PRCC, 0/16 (0%) ChRCC, and 1/19 (5.3%) ONC. Cytoplasmic caveolin-1 was detected in 16/22 (72.7%) CCRCC, 13/20 (65%) PRCC, 8/16 (50%) ChRCC and 13/19 (68.4%) ONC. Membranous caveolin-1 expression correlated with tumor size (Pearson correlation = 0.266, p = 0.043). There was no correlation between membranous or cytoplasmic caveolin-1 expression and other pathological parameters, including Fuhrman nuclear grade, or TNM stage. Conclusion: Caveolin-1 exhibits distinct subcellular localization in different renal tumors. Membranous caveolin-1 is most commonly detected in CCRCC, rarely found in PRCC and ONC, and is absent in ChRCC. This finding suggests that caveolin-1 may play an important role in the pathogenesis of CCRCC. [Table: see text]