bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low rate of progressive disease in metastatic gastric cancer using tandem chemotherapy with four active compounds
Authors: Wormann B. J. , Pies A. , Petersen P. 
Published: March 2020

14069 Background: Taxanes and irinotecan have significantly increased the therapeutic options in the treatment of metastatic gastric cancer. However, the potential of all active substances is highest in first - line treatment. The rate of second remissions is low and survival after relapse is short. We performed a phase II study incorporating 5FU, irinotecan, cisplatin and docetaxel in a tandem protocol for first line treatment of patients with metastastic adenocarcinoma of stomach or cardia. Methods: Chemonaive patients received a 30-minute infusion of irinotecan 80 mg/m2 followed by IV bolus leucovorin 20 mg/m2 and infusional 5FU 2000 mg/m2 over 24 hours on days 1, 8 and 15. The second block included docetaxel 25 mg/m2 over 60 minutes followed by a 30-minute infusion of cisplatin 40 mg/m2 on days 29, 36 and 43. Patients were scheduled to receive two complete cycles. Primary objective was evaluation of remission rate. Further objectives were toxicity and overall survival. Results: 32 patients were included, 25 patients are currently evaluable. The median age was 56 years (36 - 72), 10 female and 15 male patients. 10/25 (40%) patients achieved a partial remission, 3 of these 10 patients had a very good partial remission. 13 (52%) patients had stable disease, and 2 (8%) patients progressed early. Main toxicities grade ≥ 3 were diarrhea (8/50 cycles), nausea and vomiting (3/50), neutropenia (2/50), anemia (1/50) and renal insufficiency (1/50). The median survival time was 11.7 months. Conclusions: This treatment schedule includes the four most active substances in the treatment of metastastic gastric cancer in a tandem protocol. Only 2/25 patients had progressive disease under therapy. Toxicity was moderate. Dose intensication may further increase the remission rate. No significant financial relationships to disclose.
A phase II trial of oblimersen sodium (G3139) in combination with doxorubicin (DOX) in advanced hepatocellular carcinoma (HCC). NCI protocol # 5798
Authors: Knox J. J. , Chen E. , Feld R. , Nematollahi M. , Pond G. R. , Cheiken R. , Gill S. , Zwiebel J. , Moore M. 
Published: March 2020

14072 Background: Advanced HCC is refractory to most standard forms of chemotherapy, however responses to DOX are seen. The bcl-2 protein confers resistance to apoptosis in cancer cells and is important in tumor progression and resistance to chemotherapy. The bcl-2 antisense oligonucleotide, G3139 (G), has been shown to enhance the activity of DOX in tumor models by blocking bcl-2 synthesis. This argues for evaluating G + DOX in combination in HCC. By decreasing tumor bcl-2 protein levels, HCC may be sensitized to the apoptotic effects of DOX. Methods: We completed a phase II trial evaluating treatment with G at 7 mg/ kg for 7 days cont. i.v. infusion (d1–8) plus DOX at 45 mg/m2 i.v. bolus d5, every 28 d (as determined from our phase I HCC study). Eligible patients (pts) had path-confirmed, measurable, advanced HCC. Minimal eligibility included Childs-Pugh A cirrhosis, adequate hematological (hem) parameters and ECOG PS <2. Tumor biopsies for correlative studies were obtained at baseline and cycle 1 d 4 in consenting pts. Results: 19 patients were accrued, 1 was ineligible, 18 evaluable for toxicity, 17 evaluable for response; receiving a median (med) of 2 cycles (range 1,10). Risk for HCC was 39% HBV, 22% HCV, 17% alcohol, 22% other. Most common toxicities were hem and could be attributed to both G+DOX and to G alone. Overall grade 3–4 toxicities seen were: ANC- 67% (med nadir d 24–25), lymphopenia - 44%, thrombocytopenia - 6%, transaminitis - 33% and grade 1–2 G-fever - 67%. No responses were seen and the trial was stopped at stage 1. Six patients (35%) had stable disease, with one pt completing 10 cycles as per protocol (pt # 22). Med TTP is 1.8 months (1.7-NA) and 6-month PFS is 17.2% (5.3–56.4). 18 of 19 pts have died with med OS of only 5.4 months (2.7–11.6). Correlative studies on 3 available pts’ paired tumor biopsies showed absent baseline bcl-2 expression but moderate expression of both bcl-xl and BAX protein and with no change after exposure to G (includes pt #22). Conclusions: G + DOX is inactive in HCC at this dose and schedule. The overlap of hem toxicity may have resulted in suboptimal DOX dosing in HCC. Low baseline bcl-2 tumor expression relative to bcl-xl seen may suggest a relative insensitivity to the effects of bcl-2 inhibition in these HCC tumors. [Table: see text]
Second-line chemotherapy with mitomycin C and S-1 in patients with advanced gastric cancer
Authors: Shin D. , Lee S. , Park S. , Bang S. , Cho E. , Lee J. 
Published: March 2020

14083 Background: S-1, a fourth generation oral fluoropyrimidine that mimics infusional 5-fluorouracil, has demonstrated activity against advanced gastric cancer. Based on a single agent activity and in vitro synergy between mitomycin C (MMC) and 5-fluorouracil, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for previously treated, advanced gastric cancer. Methods: Patients with measurable gastric cancer, progressive after at least one prior chemotherapy for metastatic disease, were treated with MMC 7 mg/m2 on day 1 and S-1 40 mg/m2 twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks, for up to 4 cycles. Objective response rate was the primary endpoint and was evaluated every 2 cycles of chemotherapy. With a single-stage phase II design, at least 25 patients were required. Results: Of the 26 patients registered, 24 patients were evaluable for response and 26 for safety. Eighteen patients (69%) were previously treated with 5-fluorouracil-based chemotherapy, and 10 (39%) were treated with taxanes. The patients’ median age was 55 years (range, 38–73) and 7 (27%) had an ECOG performance status of 2. A total of 64 chemotherapy cycles were delivered (median, 2; range, 1–4). In an intent-to-treat analysis, 6 patients (23%) achieved a partial response, which maintained for 3.5 months. The median progression-free and overall survivals were 4.4 months (95% CI, 1.7–7.2) and 5.4 months (95% CI, 3.4–7.4), respectively. Major toxic effects included stomatitis, diarrhea and fatigue, but were generally mild and manageable. No patient developed hemolytic reaction. Conclusions: Second-line chemotherapy with MMC and S-1 is an effective regimen for advanced gastric cancer with an acceptable toxicity profile and a convenient administration schedule. No significant financial relationships to disclose.
Circulating chromogranin-a (CgA) as a useful marker in the diagnosis and follow up of neuroendocrine tumors (nets): An Italian multicenter observational study (cromAnet)
Authors: Dogliotti L. , De Braud F. , Delle Fave G. , Degli Uberti E. , Tomassetti P. , Gion M. , Leon A. , Torta M. , Borgna L. 
Published: March 2020

14091 The primary objective of this study was to validate the clinical significance of blood evaluation of CgA in NET patients at the diagnosis (PHASE I) and during 2 years of follow-up (PHASE II). From May 2003 to October 2004, 276 patients entered the study from 40 Italian centers: 270 were evaluable. All basal and every 3 months collected CgA blood samples were centrally measured in two reference laboratories (Orbassano-Turin and Venice) where ELISA (DAKO,Denmark) or IRMA (CIS-Schering, France) were performed to look at the correlation between the two methods and their sensitivity and specificity. Lab results at the baseline have been recently published (Leon et al., Intern. J. Biol. Markers, 2005). We are now collecting all the correlations between CgA and type and place of NETs; tumor bulk; metastatization; presence or not of specific syndrome;proliferation activity (Ki67); octreoscan; tumor specific markers. 223 patients (83%) had gastroenteropancreatic tumors, whereas 24 (9%) had medullary tyroid cancer, 16 (6%) Merkel cell carcinoma and 6 parathyroid NETs, pheochromocytoma, paraganglioma. Only 26% of GEP tumors presented with specific symptoms. At the entry in the study 58% of patients had a new diagnosis, 23% were in stable disease, whereas 18% had metastatic disease. According to the recent W.H.O. histologic classification (Solcia et al, 2000), 36% specific symptomatic patients had NE tumor, 57% well differentiated cancer and only 3% poor differentiated cancer, whereas 31% not symptomatic patients had NE tumor, 48% well differentiated and 16% poor differentiated cancer. This is the largest study worldwide performed on this topic and all the data about the correlation among all patient variables and CgA blood values will be ready in April 2006. Follow-up data will be evaluable next year. [Table: see text]
Phase II study of oxaliplatin-based chemotherapy in patients with advanced gastric cancer
Authors: Vattemi E. , Pedersini R. , Kildani B. , Stocker J. , Baier S. , Cretella E. , Petric M. , Lusso M. , Graiff C. 
Published: March 2020

14119 Background: The aim of the study was to assess the toxicity and the clinical activity of oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks in patients with advanced gastric cancer. Methods: 26 patients with recurrent and/or metastatic gastric cancer were enrolled. They received oxaliplatin 85 mg/mq on day 1, FA 200 mg/mq as a 2 h infusion followed by bolus 5-FU 400 mg/mq repeated for 2 consecutive days (FOLFOX-4). Treatment was repeated every two weeks until disease progression or limiting toxicity. Results: Patients had a median age of 62 years (range, 74–40); 19 patients had a PS of 0–1. Twenty patients had a newly diagnosed metastatic disease and 6 patients had recurrent disease. The median number of sites involved was 2. Four patients had prior adjuvant chemotherapy with cisplatin, 5-FU and epirubicin. So far, 22 of 26 patients are evaluable. The mean number of cycles was 8.6 (range, 2–15). One complete response (4.5%) and 9 partial responses (41%) were observed for an overall response rate of 45%. Stable disease was seen in 8 patients (36%) and disease progression occurred in 4 patients (18%) Median progression free survival was 4.7 months and median overall survival was 9.8 months. No WHO grade IV toxicity occurred and the only grade III toxicity was peripheral neuropaty (10%). The most commonly reported hematologic event was grade II neutropenia (20%) and trombocytopenia (15%). Conclusions: FOLFOX-4 regimen shows good efficacy and accetable safety profile in advanced gastric patients. No significant financial relationships to disclose.
Improved survival in patients with locally advanced esophageal cancer utilizing a multidisciplinary approach
Authors: Skaff Z. , Hannigan K. , Hughes S. , Atabek U. , Shum M. , Kankipati S. , Elkhoury M. , Hageboutros A. 
Published: March 2020

14130 Background: Locally advanced esophageal cancer studies have reported a three year overall survival rate of 32% with a median survival of 16 months. These patients were treated with combined chemotherapy and radiation with surgery, when applicable. We conducted this study to determine whether using an individualized, multidisciplinary approach affected survival outcomes in patients treated for locally advanced esophageal cancer. Methods: All patients treated for locally advanced esophageal cancer were retrospectively identified from our database at The Cancer Institute of New Jersey at Cooper University Hospital. All patients were presented and discussed in a multidisciplinary gastrointestinal tumor board conference. After a consensus was obtained, a treatment plan was established for each patient based on his or her respective clinical characteristics: stage, performance status, medical suitability for surgery and resectabilty. Results: A total of 23 patients (median age: 66 years [range, 55–88 years]) were identified, the histopathologic diagnosis was adenocarcinoma in 13 and squamous cell carcinoma in 10 cases. TNM staging was as follows: 18 (78.3%) stage II or III and 5 (21.7%) stage IV. Initial management included esophagectomy for 9 (39.1%), 6 of which received preoperative chemotherapy (5-FU) and three received postoperative adjuvant chemotherapy, 14 (60.9%) received only combined chemotherapy (average four cycles of 5FU 1000 mg per square meter of body surface + Cisplatin 75 mg per square meter of body surface) and radiation at doses 50–64 Gy. Overall median survival was not reached since only five patients (21.7%) have died. The 1- year and 2-year survival rates were 87% and 74% respectively. Median follow-up for patients who received combination chemotherapy and radiation vs. surgery with preoperative therapy was 29 and 41 months, respectively. Conclusion: This retrospective analysis shows promising outcomes compared to published data supporting the role of an individualized, multidisciplinary approach in the management of each patient with esophageal cancer. No significant financial relationships to disclose.
Phase 1 study of paclitaxel, cisplatin, and 5-fluorouracil (TCF) in patients with advanced gastric cancer
Authors: Yokoi K. , Omura K. , Hirano M. , Hara T. , Munemoto Y. , Asada Y. , Sakamoto J. 
Published: March 2020

14134 Background: Paclitaxel is effective against gastric cancer with serosal involvement and/or peritoneal dissemination. Combination of cisplatin and 5-fluorouracil is also active against advanced gastric cancer. Therefore, we designed a phase I trial of a combination of paclitaxel, cisplatin and 5-fluorouracil (TCF) to explore potential synergistic effect. Methods: Eligible patients had metastatic or unresectable gastric cancer with up to 1 prior chemotherapy regimen. The fixed dose of cisplatin 25 mg/m2 and paclitaxel 80 mg/m2 with escalation dose of 5-fluorouracil from 300 mg/m2 to a maximum of 600 mg/m2 on days 1, 8 and 15 of a 28 day schedule were administered. MTD and anti-tumor activity were evaluated. Results: No grade 3 or 4 toxicities at least possibly related to the treatments resulting in DLT were observed on every dose level. The clinical effects were determined in 3 patients with measurable lesions out of 7 cases. There were 2 partial responses, and disease stabilization was seen in one patient. Conclusions: Combination of paclitaxel, cisplatin and 5-fluorouracil (TCF) is considered to be feasible, well tolerated and active in patients with advanced gastric cancer and warrants further examination in a phase II trial. No significant financial relationships to disclose.
A SEER database analysis of conditional survival for prostate cancer patients
Authors: Luh J. Y. , Wang S. J. , Fuller C. D. , Thomas C. R. 
Published: March 2020

14506 Background: Survival probability changes for patients who have already survived one or more years following diagnosis, and is more accurately represented by conditional survival. The specific aims of this study were to determine the 5-year conditional survival rates for prostate cancer patients. Methods: Using the Surveillance, Epidemiology, and End Results (SEER 11) database from the NCI, we analyzed 66,822 prostate cancer patients diagnosed between 1988 and 1994 that were staged using the SEER-modified AJCC staging system (3rd edition). Using the life table method, we computed observed 5-year conditional survival, stratified by stage, age, and race, for patients who had already survived 0 to 5 years after diagnosis. Results: For each category, we compared baseline 5-year observed survival at diagnosis with 5-year observed conditional survival after having already survived 5 years. Survival decreased from 79% to 67% for Stage I, decreased from 80% to 71% for Stage II, decreased from 83% to 75% for Stage III, but increased from 38% to 49% for Stage IV patients. Survival rates did not change for patients <70 years (79–80%), but decreased from 61% to 55% for patients >70 years old. Although blacks (60–62%) had lower survival than whites (69–71%), no race had any appreciable change in their conditional survival for those who had survived 5 years from diagnosis. Conclusions: For prostate cancer patients who have already survived some time after diagnosis, the expected 5-year conditional survival increases for Stage IV patients, but decreases for other stages and for older patients. Conditional survival can provide more accurate longer term prognostic information for prostate cancer patients who have already survived a number of years after diagnosis. No significant financial relationships to disclose.
PSA flare-up in patients with hormone-refractory prostate cancer (HRPCA) receiving docetaxel-based chemotherapy: Incidence and differentiation from progressive disease
Authors: Sahi D. , Ohlmann C. H. , Cordia I. , Engelmann U. , Heidenreich A. 
Published: March 2020

14523 Background: Docetaxel-based chemotherapy displays the standard therapy for patients with hormone-refractory prostate cancer. A subset of patients will experience an initial PSA increase after initiation of therapy followed by a subsequent PSA decrease. The aim of our study was to investigate the incidence of this phenomenon and to identify factors that differentiate the flare-up from progressive disease. Methods: We retrospectively analyzed the patient records of 46 patients who received docetaxel as monotherapy or in combination with either mitoxantron or estramustine for hormone-refractory prostate cancer. PSA flare-up was defined as an initial PSA increase of more than 25% after initiation of therapy over baseline followed by a PSA decrease of at least 75% compared to the maximum increase over baseline. Progressive disease was defined as a PSA increase of at least 25% over baseline in patients with no PSA response which had to be confirmed four weeks later. Results: Of 46 patients who received docetaxel-based chemotherapy 16 (34.8%) showed a PSA decrease of at least 50%, 6 (13.0%) between 30–50%, 17 (37.0%) had stable disease and 7 (15.2%) patients experienced progressive disease. An initial PSA increase followed by a subsequent PSA decrease was seen in 6 (13.0%) of the patients. Median PSA increase compared to baseline was 81.0% (25–239). The median following PSA decrease was 110.5% (77–160) compared to the initial increase. Median PSA doubling times of patients with PSA flare up or progressive disease were 113.3 and 100.7 days (p = 0.7941), respectively. Conclusions: PSA flare-up seems to be a common phenomenon in patients being treated with docetaxel-based chemotherapy for hormone-refractory prostate cancer. In order not to prevent those patients from a subsequent PSA decrease by early cessation of therapy it would be useful to discriminate them from patients with progressive disease. According to the results of our study PSADT does not differ between patients with flare-up or progressive disease and can therefore not be used to distinguish between the two. No significant financial relationships to disclose.
SPC2968—A novel Hif-1α antagonist for treatment of clear cell renal cell carcinoma
Authors: Westergaard M. , Hansen H. F. , Thrue C. A. , Hansen J. B. , Kjaerulff L. S. , Straarup E. M. , Olsen O. , Dalby L. W. , Hildebrandt-Eriksen L. , Kearney P. 
Published: March 2020

14581 Background: SPC2968 is a short (16-mer), oligonucleotide antagonist of Hif-1α mRNA in which potency has been enhanced through incorporation of Locked Nucleic Acid. Over-expression of Hif-1α has been correlated with increased vascularisation, metastatic potential and poor clinical outcome in a variety of malignancies, including Renal Cell Carcinoma (RCC) of clear cell aetiology, where Hif-1α dysregulation, brought about by mutations in the von Hippel Lindau gene, appears to play a major pathogenic role. Methods: In vitro, human cancer and endothelial cells grown under hypoxic conditions were used to evaluate the effect of SPC2968 on mRNA and protein to Hif-1α as well as phenotypic effects, measured by quantitative polymerase chain reaction (QPCR), Western blotting and biochemical/cellular assays. QPCR was also used to measure mRNA levels in SPC2968-treated mice, while the effects of the drug on tumour growth and vascularisation were evaluated in xenografts. To assess biodistribution in vivo, tritium-labelled SPC2968 was injected intravenously. Results: In vitro, SPC2968 at 1nM reduced both mRNA and protein levels of Hif-1α in cancer cell lines and downregulated two downstream targets of Hif-1, VEGF and MMP-2.Treatment also induced apoptosis in tumour cells and prevented tube formation by endothelial cells in vitro. Parenteral administration of SPC2968 in mice yielded potent inhibition of Hif-1α and VEGF mRNA in several tissues, including kidney, liver, and colon. Radioactively labelled SPC2968 distributed to kidney, liver, colon, bone marrow, lymph nodes and skin. Preclinical studies investigating acute and sub-acute toxicity and safety pharmacology of SPC2968 are completed, and SPC2968 was well tolerated. Conclusions: SPC2968 is an effective suppressor of Hif-1α mRNA and Hif-1α-regulated genes in vitro and in vivo and has shown good tissue biostability and biodistribution in rodents. Preclinical safety studies have been completed, and SPC2968 is ready for clinical testing. A phase I/II, dose-escalating study of SPC2968 in clear cell RCC in the US and the EU is planned to be submitted by mid 2006. [Table: see text]
Safety and efficacy of the combination of high-dose calcitriol, docetaxel and aoledronic acid in hormone-refractory prostate cancer (HRPC): Interim report of a phase II trial
Authors: Shamseddine A. , Makarem J. , Abdel Khalik Z. , Bulbul M. , Taher A. , Khawli R. , Hemadeh K. , El-Saghir N. 
Published: March 2020

14600 Background: The purpose of this study is to assess the efficacy and safety of Calcitriol, Docetaxel and Zoledronic acid in patients with metastatic HRPC. The primary endpoint of the study is the toxicity profile. Secondary endpoints include prostate specific antigen PSA response and time to disease progression. Methods: 16 patients with HRPC were enrolled. All patients had confirmed diagnosis of prostate cancer and no previous cytotoxic therapy. All patients signed an informed consent. Patients received oral Calcitriol 0.5μg/kg on day 1 on weekly basis six out of eight-week cycles, Docetaxel 36mg/m2 on day 2 on weekly basis six out of eight-week cycles, and Zoledronic acid 4mg intravenously on weeks 1 and 5 of every 8-week cycle. Results: A total of 52 cycles were administered and toxicity was acceptable. No treatment-related mortality was encountered. No grade IV anemia, neutropenia, thrombocytopenia or diarrhea was reported. No grade IV gastrointestinal toxicities or thromboembolic events were reported. Grade IV infection was seen in 2 (3.8%) cycles (herpetic esophagitis and listeria meningitis). Grade III neutropenia was seen in 2 cycles (3.8%). Grade III diarrhea was seen in 1 cycle (1.9%) and grade II diarrhea in 4 cycles (7.7%). Grade II to III nausea and vomiting was reported in 8 cycles (15.4%). Grade II to III sensory neuropathy was noted after 17 cycles (32.7%). Grade III fatigue was reported in 5 cycles (9.6%). 14 patients were eligible for response analysis. Overall PSA response rate of our patients was 57.2%. Median time to disease progression was 6.5 months (range 2–15). One year survival was 57.1% (8 out of 14 patients). Conclusions: This interim analysis showed that the addition of Calcitriol to Docetaxel showed an acceptable safety profile as compared to Docetaxel regimens alone with less incidence of neutropenia and diarrhea. Previous studies using Docetaxel alone has reported higher incidence of neutropenia reaching 43–56% and grade III to IV diarrhea (10–34%). Our study suggests that Calcitriol might have a protective effect against the Docetaxel toxicities. No significant financial relationships to disclose.