bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vinflunine in patients with advanced unresectable hepatocellular carcinoma and liver impairment
Authors: Saliba F. , Paule B. , Adam R. , Castaing D. , Azoulay D. , Ogier I. , Pinel M. , Cadic V. , Delgado M. 
Published: March 2020

15023 Background: In patients (pts) with advanced hepatocellular carcinoma (HCC) and liver cirrhosis, systemic chemotherapy has most commonly been associated with a very low response rate and high toxicity leading to death from liver failure. Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class which has demonstrated clinical activity in several tumour types. Methods: A phase I trial was designed to determine VFL dose adjustments in cancer pts with various degrees of liver dysfunction. A high number of pts with HCC and concomitant liver cirrhosis (Child-Pugh grades A and B) were included in the study (18/30 pts). Therefore, a subgroup analysis was carried out in order to determine the safety profile of VFL in these pts (NCI-CTC version 2.0) and to estimate its anti-tumour activity (WHO criteria). Results: Eighteen pts (15 males) of median age 60.7 [26.4–75.3] years with advanced stage and unresectable HCC were treated with VFL. All these pts were outside Milan criteria and ineligible for liver transplantation. Thirteen pts had been previously treated by chemotherapy. The WHO performance status was 0: 11 pts, 1: 5 pts, 2: 2 pts. They received a median number of 4 cycles [1.0–31.0] of different doses of VFL according to the severity of the underlying liver impairment 320 mg/m2 (3 pts), or 250 mg/m2 (6 pts) or 200 mg/m2 (9 pts). One partial response (PR) was observed while 11 pts (61.1%) had stable disease (SD) yielding a disease control rate (PR + SD) of 66.7%. The median progression free survival was 3.4 months [95% confidence interval (CI): 2.6–6.0]. Haematological toxicity: grades (G) 3 anaemia = 4 pts, G3/4 neutropenia = 11 pts, G3 thrombocytopenia = 7 pts, no febrile neutropenia. Other G3 toxicities included G3 abdominal pain (2 pts), constipation (3 pts), neutropenic infection (1 pt). Six pts experienced G3 (5 pts) or 4 (1 pt) fatigue. Conclusions: Vinflunine can be given safely at 320 mg/m2 or 250 mg/m2 or 200 mg/m2 in pts with unresectable advanced HCC with different degrees of liver impairment. The disease control rate is promising (66.7%). No significant financial relationships to disclose.
Treatment with bevacizumab (BEV) upregulates expression of the transcription factor Sp1 and its downstream target genes in human carcinoid cells: Molecular basis of the synergistic antiangiogenic activity of bevacizumab and mithramycin A (MIT)
Authors: Zhang J. , Jia Z. , Wang L. , Li Q. , Xiangdong L. , Xie K. , Yao J. C. 
Published: March 2020

15031 Background: Our previous studies show that human carcinoid cells overexpress pro-angiogenic factors, vascular endothelial growth factor A (VEGF), and transcription factor Sp1 plays a critical role in VEGF inducible and constitutive expression. However, the impact of antiangiogenic therapy on the Sp1/VEGF pathway remains unclear. Method: Groups of 10 athymic BALB/c nude mice were implanted with 1.5 million human H727 carcinoid cells. Treatment with VEGF neutralizing monoclonal antibody, BEV, MIT, or BEV + MIT was initiated once implanted tumor reached 4 mm in size. Result: Treatment with BEV, suppressed human carcinoid growth in nude mice (tumor size at week 5 1280 mm3 vs 480 mm3; p < 0.001). Gene expression analyses revealed that this treatment substantially upregulated the expression of Sp1 (7 folds) and its downstream target genes, including VEGF (5 folds) and epidermal growth factor receptor (4 folds), in tumor tissues, whereas it did not have this effect on carcinoid cells in culture. Treatment with mithramycin A, an Sp1 inhibitor, suppressed the expression of Sp1 and its downstream target genes in both cell culture and tumors growing in nude mice. Median survival of mice treated with PBS, BEV, MIT, and BEV + MIT groups were 88, 112, 121, and >160 days respectively (p < 0.001). Combined treatment with bevacizumab and mithramycin A produced synergistic tumor suppression, which was consistent with suppression of the expression of Sp1 and its downstream target genes. Conclusion: Treatment with bevacizumab may block VEGF function but activate the pathway of its expression via positive feedback. Given the fact that Sp1 is an important regulator of the expression of multiple angiogenic factors, bevacizumab-initiated upregulation of Sp1 and subsequent overexpression of its downstream target genes may affect the potential angiogenic phenotype and effectiveness of antiangiogenic strategies for human carcinoid. No significant financial relationships to disclose.
Late term renal complications related to chemoradiotherapy in patients with gastric cancer
Authors: Mayadagli A. , Seseogullari O. O. , Gemici C. , Ozkan A. , Parlak C. , Gocen E. 
Published: March 2020

15033 Background: The aim of this study is to evaluate late term renal complications of the combined treatment with chemoradiotherapy, according to the scheme of McDonald et al, in patients diagnosed with gastric cancer, after radical curative surgery. Methods: Totally 44 patients who administered to our clinic between years 2003 and 2004, with the diagnosis of gastric cancer, and with the age-adjusted creatinine clearance test (CCT) results within normal range, were enrolled into the study. Surgical procedure was subtotal gastrectomy in 34 patients (63,6%), and total gastrectomy in 16 patients (36,4%). Total 4600 cGy radiotherapy was administered to all patients through parallel-opposed AP-PA fields in 23 fractions concomitant with chemotherapy according to the scheme of McDonald et al. One year after the completion of the treatment, a technetium 99-m renal scintigraphy (DMSA) and CCT were performed to all patients whose renal functions were within normal limits. Results: Median age in the study was 52 (22–78). 34 patients (77,3%) were male and 10 (22,7%) were female. TNM stages were stage II in 15 (34,1%), IIIA in 21 (47,7%), IIIB in 4 (9,1%), and IV in 4 cases (9,1%). CCT measured 1 year after the treatment was low in 13 patients (29,6%), and within normal range in 31 patients (70,4%). Renal scintigraphy revealed damage at one pole in 32 patients (72,7%), damage at bilateral renal poles in 8 patients (18,3%), and it was normal in 4 patients (9%). Renal damage was higher in left kidneys than right kidneys (89,9% vs. 15,4%). There was a correlation between CCT values and scintigraphical findings. Damage in bilateral renal poles was higher in cases with low CCT than in cases with normal values (85,7% vs. 15,4). In general, there were no statistically significant relationship between late term renal complications and sex, and grade III treatment-related gastrointestinal toxicity. However, the relationships with age, extent of surgery reached statistical significance (p=0.009, and =0.006). Renal damage was notably higher in older patients, and in patients who underwent total gastrectomy. Conclusions: Since postoperative chemoradiotherapy is a novel modality for the treatment of gastric cancer, more studies are required in order to evaluate chronic toxicities. No significant financial relationships to disclose.
Combination treatment of paclitaxel, cisplatin and infusional 5-fluorouracil (PCF) as first-line chemotherapy for metastatic or recurrent gastric cancer: Prospective multicenter clinical trial
Authors: Jin M. , Zhang X. D. , Shu Y. Q. , Liang J. , Yang J. W. , Chen L. , Cao W. G. , Shi G. M. , Guo C. Y. , Zhang F. C. 
Published: March 2020

15035 Background: Paclitaxel has been shown to be effective in patients with advanced gastric cancer. We assess the combination of paclitaxel (Anzatax®, Mayne Pharma), infusional 5-fluorouracil and Cisplatin as first-line chemotherapy for metastatic or recurrent gastric cancer. Methods: Patients with previously untreated metastatic gastric adenocarcinomas are eligible. Fifty patients received paclitaxel (Anzatax®, Mayne Pharma) 150mg/m2 by 2-hour infusion day 1, cisplatin 15 mg/m2 daily days 1 through 5, and 5- fluorouracil by continuous infusion at a dose of 600 mg//m2 daily days 1 through 5. Cycles were repeated every 3weeks until progression. Objective tumor responses, duration of response, time to progression, and toxicity profile are the end points evaluated in this study. Results: Total 50 patients were enrolled (41 men, 9 women). The median age was 59 years (range 32 - 75). All patients had ECOG performance status (PS) 0–2 and adequate organ functions. 50 patients completed one-six cycles (mean 3 cycles). Forty-four patients were evaluable and all patients were assessable toxicity. In these 44 assessable patients, 1 CRs and 14 PRs were obtained, resulting in an overall response rate of 34%. 19 patients (43.2%) had stable disease, and 3 patients (8.9%) progressed. The tumor control rate was 77.3%. The median time to progression(TTP) was 5 months. The major (Grade 3–4) toxicities were neutropenia (22%) and anorexia (4%). There were no treatment-related deaths were recorded in all patients. The median and overall survival times are now being followed up and the results will be announced during the ASCO 2007 annual meeting. Conclusion: The combination of paclitaxel (Anzatax®, Mayne Pharma), cisplatin,and 5-FU has substantial antitumor activity in advanced gastric cancer. The toxicity of this regimen is within acceptable range, but no remarkable response rate was noted. Paclitaxel is an important new agent in the treatment of gastric cancer, and further evaluation of this agent in combination chemotherapy is warranted. No significant financial relationships to disclose.
Pancreatic neuroendocrine tumors: Can the WHO staging system be simplified
Authors: Ferrone C. , Tang L. H. , Tomplinson J. , Klimstra D. S. , Coit D. G. , Brennan M. F. , Allen P. J. 
Published: March 2020

15038 Background: The current World Health Organization (WHO) classification system for well-differentiated pancreatic endocrine neoplasms (PENs) is complex, and incorporates both stage- and grade-specific information. The aim of this study was to compare separately the prognostic value of stage and grade in a large single institution study of PENs. Methods: A prospectively maintained database from a single institution identified 183 patients who underwent operative treatment for a PEN between 1982–2005. Tumors were staged (<2 cm primary, =2 cm primary, metastatic disease) and graded (Low: no necrosis and <2 mitoses/50 high-power fields - HPF. Intermediate: presence of necrosis and/or =2 mitoses/50 HPF) with a simplified schema. The influence of tumor stage and grade on disease recurrence and disease-specific survival (DSS) was assessed. Results: Median age of the 183 patients was 56 years and 53% were women. Median length of follow-up was 44 months. At the time of presentation 35 patients (19%) had tumors <2 cm without evidence of metastatic disease (<2 cm), 96 patients (52%) had tumors =2 cm without metastases (=2 cm), and 52 patients (29%) were found to have nodal or distant metastatic disease (mets). Size of the primary tumor was not associated with the presence of nodal metastases (mean diameter: N0, 4.8 cm vs. N1, 4.7 cm: p=0.96) and 5/19 patients with tumors =2 cm had positive nodes. Grade was determined in 98% of patients (n=180). Low-grade tumors were present in 102 patients (56%) and intermediate grade tumors in 78 patients (42%). Earlier stage tumors were more likely to have low grade disease (% Low grade: <2 cm, 83%; =2 cm, 61%; mets, 28%: p <0.001). For all patients, tumor stage and grade were associated with survival (5-yr DSS: Stage: <2 cm, 100%; =2 cm, 90%; mets, 70%: p<0.001. Grade: Low, 98%; Intermediate, 70%: p<0.001). For patients with tumors =2 cm or with mets, grade was associated with survival within each sub-group (5-yr DSS =2 cm: Low 97% vs. Intermediate 80%: p<0.001, Mets: Low 93% vs. Intermediate 62%: p=0.05). Discussion: Stage and grade are important independent prognostic factors in patients with PENs. More accurate prognostic information can be provided by combining tumor size and metastases with simple grading information based on necrosis and mitotic rate. No significant financial relationships to disclose.
Phase II study of paclitaxel, cisplatin, and 5-FU combination chemotherapy in patients with advanced gastric cancer
Authors: Cho S. , Shim H. , Lee S. , Ahn J. , Yang D. , Kim Y. , Park C. , Lee J. , Chung I. , Kim H. 
Published: March 2020

15052 Background: Taxane has been used widely in advanced gastric cancer, but toxicities are problematic. To avoid the bone marrow suppression, docetaxel could be replaced paclitaxel to reduce bone marrow suppression and to improve the efficacy, we planned to augmentation of the dose intensity. This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Methods: Patients with histologically confirmed gastric adenocarcinoma, ECOG PS = 2, at least one measurable lesion and adequate organ functions were eligible. Paclitaxel (175 mg/m2) and cisplatin (75 mg/m2) were given as a 1-h intravenous infusion on day 1, followed by 5-FU (750 mg/m2) as a 24-h continuous infusion for 5 days. This cycle was repeated every 3 weeks. Results: Forty-five eligible patients (median age 56 years) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 20 (48.8%), a complete response in two, and a partial response in 18 patients. The median time to progression was 6.9 months (95% CI, 5.86–7.94), and the median overall survival was 13.1 months (95% CI, 8.83–17.37). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in 67 cycles (25%). Febrile neutropenia developed in three patients (7.3%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but grade 3 or 4 toxicity was not seen. Conclusions: The combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer. No significant financial relationships to disclose.
Radio-frequency ablation (RFA) is equivalent in therapeutic effect but safer compared to microwave coagulation therapy (MCT) for hepatocellular carcinoma
Authors: Beppu T. , Masuda T. , Ishiko T. , Hayashi H. , Sugiyama S. , Doi K. , Takamori H. , Kanemitsu K. , Hirota M. , Baba H. 
Published: March 2020

15064 Background: Radio-frequency ablation (RFA) and microwave coagulation therapy (MCT) have been developed as a useful locoregional treatment for hepatocellular carcinoma (HCC). It is still unclear which ablation therapy is superior for the patients with HCC, from the viewpoint of not only short term but also long term outcome. Methods: Between January 1991 and December 2005, 430 patients with HCC were treated with ablation therapy (230 RFA and 200 MCT) in our institution. Enroll criteria of this therapy were as follows; 1) unresectable HCCs, 2) each smaller than 3 cm, 3) up to three nodules, 4) without vascular invasion. Either percutaneous (P), endoscopic (E) or open (O) approach was selected individually based on location, size, number, or other factors. Treatment was repeated until complete ablation of HCC. Results: 1. Proportion of Child B or C was 62% and 60%; Stage III or IV was 56% and 58% in the patients with RFA and MCT, respectively. 2. Average tumor size and tumor number was 27mm/2.5 and 26mm/1.9 in the two groups. 3. Approaches were P: 55%, E: 33%, O: 12% in RFA and P: 48%, E: 30%, O: 22% in MCT. 4. Number of treatment was 1.1 in RFA and 1.2 in MCT. 5. Recurrence rate at the therapeutic site was 8% in RFA and 12% in MCT. Especially, endoscopic RFA provided a quite low recurrence rate (3%). 6. Cumulative 5-year survival was 52% versus 45% in the two groups. 7. Complication rate was significantly lower in RFA (5%) compared to MCT (11%). Intraabdominal tumor seeding (1% in MCT) and liver abscess formation (4% in MCT) was never encountered in RFA. Conclusions: Radio-frequency ablation for hepatocellular carcinoma is a safer procedure and can provide a similar favorable long- term prognosis compared to microwave coagulation therapy. No significant financial relationships to disclose.
Phase I/II study of combination chemotherapy with S-1 and cisplatin every 3 week schedule in patients with metastatic or recurrent gastric cancer
Authors: Lee J. , Kang H. , Kang Y. , Ryu M. , Chang H. , Kim T. , Sohn H. , Kim H. , Lee J. 
Published: March 2020

15066 Background: S-1 plus cisplatin has been reported to be highly active in advanced gastric cancer (AGC). The objectives of this study were to define the maximal-tolerated dose (MTD) of S-1, given for 2 weeks separated by 1 week rest, with a fixed dose of cisplatin, and to determine the activity and safety of this combination regimen at the recommended dose (RD) when used as the first line treatment of AGC. Methods: Cisplatin was fixed at a dose of 60 mg/m2 on D1 and the starting dose of S-1 was 30 mg/m2 bid (level I) on D1 to D14 every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 50 mg/m2 bid (level V) unless MTD was achieved. At every level, a cohort of 3 patients (pts), which could be expanded to 6 pts, was studied. Dose-limiting toxicities (DLTs) were assessed for the first 2 cycles. Results: From February 2004 to January 2006, 62 eligible pts were enrolled. In phase I (N=21), DLTs occurred at level V (S-1 50 mg/m2 bid), with 2 of 3 pts developing G3 diarrhea or febrile neutropenia. The RD was determined at level IV (45 mg/m2 bid) because only 1 DLT occurred out of 6 pts at this level. After the first 20 pts (series I) were enrolled in phase II, the protocol was amended; the S-1 dose was reduced down to 40 mg/m2 bid (level III, series II, N=23) because of poor bone marrow recovery and resultant treatment delay. At the time of analysis, a total of 272 cycles of chemotherapy were administered. The median age was 52 years (28–70) and ECOG PS was 0/1 in 98% of pts. The objective response was observed in 20(47%; 95% CI, 36–66%) of 43 pts. SD was achieved in 15 (35%) pts. With a median FU of 12.1 months (range 9.8–23.3) for all survivors, median PFS was 5.3 months (95% CI, 4.6–6.0 months) with a median OS of 10.0 months (95% CI, 5.1–14.8 months). G3–4 toxicities included neutropenia (33%), anemia (31%), anorexia (24%), and asthenia (14%); however severe febrile neutropenia, abdominal pain, and stomatitis were never observed. Conclusions: The cisplatin plus S-1 regimen incorporating 2-weeks on and 1-week off is highly active against gastric adenocarcinoma with favorable toxicitiy profiles in Korean patients. No significant financial relationships to disclose.
Follow up of a multicenter phase II study of sequential paclitaxel and S-1 (TXL/S1) as postoperative adjuvant chemotherapy for gastric cancer (GC)
Authors: Tsuburaya A. , Murata N. , Kimura M. , Ueda Y. , Takahashi M. , Yoshino S. , Takagi M. , Morita S. , Sakamoto J. 
Published: March 2020

15084 Background: Of patients who undergo R0 resection for GC with serosal invasion (T3–4), more than half recur mainly in the peritoneum, while TXL and S1 exhibited efficacy for diffuse type and peritoneal metastases in the phase II studies. Primary analysis of the sequential chemotherapy with TXL/S1 had shown its safety and tolerability, its survival benefit is being tested in a large phase III study (the SAMIT trial) with oral fluoropyrimidines as controls. The analysis for survival of this preceding phase II study is performed. Methods: Eligibility criteria included histologically proven GC; sT3–4; sN0–2; M0 (except peritoneal cytology: CY); post D2–3 gastrectomy and R0–1; ECOG PS 0–1; and 20–80 years old. On postoperative day 14 to 56, patients received 3 courses of weekly TXL (80mg/m2 on day 1, 8 for the 1st course and on day 1, 8, 15 for the 2nd and 3rd courses, repeated every 3 or 4 weeks) followed by 4 courses of S1 (80mg/m2 daily for 2 weeks, repeated every 3 weeks). The primary endpoints were % of patients who completed all 7 courses (compliance) to see whether the lower 95% confidence limit of compliance was greater than 69% and incidence of severe toxicities and the secondary endpoints were 3-year survival and toxicities. Results: 50 patients were accrued from May 2003 to March 2004. The median age was 63 (range 34–74); male/female: 34/16; pT2/T3/T4: 1/44/5; CY0/CY1: 4/46; f-stage2/3a/3b/4: 12/15/16/7. The overall compliance was 84%. Median follow up time was 1063 days for survivors (694–1332) and 1030 days for all. Three-year DFS were 64.6% for all, 66.1% for CY0 and 50.0% for CY1. Conclusions: Sequential TXL/S1 may serve as an active adjuvant for gastric cancer patients especially who are at high risk for peritoneal spread. No significant financial relationships to disclose.
Pilot study of selective internal radiation therapy (SIRT) for patients with unresectable neuroendocrine liver metastases (NETLM)
Authors: King J. , Quinn R. , Glenn D. , Liauw W. , Janssen J. , Morris D. 
Published: March 2020

15096 Background: Few effective treatment options exist for inoperable NETLM. A prospective single-unit study assessed safety and efficacy of radioactive yttrium90 resin (SIR) in 34 patients with unresectable (NETLM). Method: Microspheres were administered via temporary percutaneous hepatic artery catheter with concomitant 7day 5-flurouracil infusion. Patients were monitored prospectively and treatment response measured by CT imaging and chromogranin A (CgA). Results: 34 patients (22 male), mean age 61 years (range 32–79) were treated with SIRT from December 2003 to December 2005. Mean follow-up 28.9 months, (95% CI 23.4 to 32.3). Complications were: post-embolitic pain and lethargy 1 week-1 month; 3 radiation gastritis, 2 of whom developed a duodenal ulcer. RECIST response on CT scan of 34 patients at 1 month: PR 9 (26%); SD 22 (65%); PD 3 (9%); 32 at 6 months, PR 7 (22%); SD 19 (59%); PD 6 (19%); 29 at 12 months CR 2 (7%); PR 3 (10%); SD 16 (55%); PD 8 (28%); 16 at 18 months, CR 4(25%); PR 1 (6%); SD 8 (50%); PD =3 (19%); 8 at 24 months, CR 4 (50%);SD 2 (25%),PD 2 (25%); 6 at 30 months, CR 2 (33%); SD 2 (33%); PD 2 (33%). CgA U/L fall from entry was: 19 (26%) at one month; 15 (43%) at 6 months; 15 (52%) at 9 months; 11 (57%) at 12 months; 8 (38%) at 24 months and 4 (80%) at 30 months. At 36 months from entry 11 (32%) have died; 8 (24%) have PD; 9 (26%) have SD and 6 (18%), (15 to 30 months) have CR on CT scan. Conclusion: SIRT is a promising treatment option for patients with in-operable NETLM. No significant financial relationships to disclose.