bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical application of immunoreactivity of dihydropyrimidine dehydrogenase (DPD) using highly specific antibody against recombinant human DPD (rhDPD) in gastric scirrhous cancer treated with S-1, new DPD inhibitory fluoropyrimidine
Authors: Shimizu T. , Yamada Y. , Shirao K. , Yasui H. , Morita H. , Tamura K. , Ozaki T. , Fukuoka M. 
Published: March 2020

14053 Background: Highly specific antibody against recombinant human dihydropyrimidine dehydrogenase (DPD) has been developed to assess immunohistochemically DPD expression in tumors. A new oral DPD inhibitory fluoropyrimidine (DIF), S-1, is reportedly effective against gastric scirrhous cancer. Objective of this study was to assess intra-tumoral levels of DPD immunohistochemically using highly specific anti-DPD polyclonal antibodies, and investigated the relationship between the immunoreactivity of DPD and the anti-tumor effects of S-1 as a DIF in gastric scirrhous cancer patients. Methods: The relationship between immunoreactivity to DPD in biopsy specimens and the effects of chemotherapy was investigated in 61 patients treated with first-line fluoropyrimidine-based chemotherapy (S-1:DIF, 5-FU:non-DIF) for gastric scirrhous cancer. Immunohistochemical staining intensity was semiquantitatively graded (− to 3+) on the basis of the proportion of positively stained cancer cells in the lesions. Results: Total 61 gastric scirrhous cancer patients (M/F: 34/27) were analyzed to date with a median age of 56 (range 30–73). Response rate (partial response) was significantly higher in patients with DPD positive tumors than in those with negative in S-1 group (45.5%, 10.0% : p<0.05), as compared with in 5-FU group (0%, 5.6%: p=0.398). According to median survival time, there was no significant difference between patients with DPD positive tumors (364 days) and those with negative (406 days; p=0.626) in S-1 group or in 5-FU group (181 days and 256 days, respectively; p=0.543). Conclusions: This study indicates that S-1 is effective even in gastric scirrhous cancer with the high level of DPD activity. Further immunohistochemical studies using DIF-based regimens are needed to confirm these results with larger numbers of patients. No significant financial relationships to disclose.
Treatment of cancer of the anal canal. The Hamburg experience
Authors: Rudat V. , Streller S. , Rades D. 
Published: March 2020

14062 Background: To compare surgical and non-surgical treatment approaches for anal cancer and to identify prognostic factors. Methods: Survival data of 214 patients with cancer of the anal canal were reviewed who were referred for radiotherapy to the Department of Radiation Oncology of the University of Hamburg, Germany between 1/88 and 3/05. 75 patients received a definitive radiochemotherapy (RCT) with 5-FU and MMC according to international standards, 43 an operation followed by RCT (OP+RCT), 37 an operation followed by irradiation (OP+RT), 25 an irradiation alone (RT) and 34 an operation alone because they refused a planned adjuvant RCT or RT. The operations had been performed by different referring hospitals in and around Hamburg. Results: The median follow-up time of the living patients was 67 months (1–200 months). The 10 year overall survival rate for RCT was 0.62 (95%CI 0.46–0.77), for OP+RCT 0.65 (95%CI 0.47–0.83), for OP+RT 0.55 (95%CI 0.37–0.74), for OP alone 0.51 (95%CI 0.26–0.75) and for RT alone 0.27 (95%CI 0.05–0.48). There was no statistical difference between the overall survival of patients who received RCT, OP+RCT and OP+RT according to Kaplan Meier analysis (log rank test, p = 0.71). Cox regression analysis was used to examine the simultaneous influence of the prognostic factors T, N, age, haemoglobin concentration before radiotherapy, gender, and grading on the survival of patients who were treated with RCT. The model (p = 0.015) revealed T and N to be the only statistically significant prognostic factors. Conclusions: The different surgical and non-surgical approaches to treat cancer of the anal canal in Hamburg obviously reflect the individual preferences of the different physicians. Statistical analysis did not show a benefit of an OP added to RCT. Prognostic factors for survival after RCT were the T- and N-stage. No significant financial relationships to disclose.
EXTRA Trial-Evaluation of capecitabine treatment with radiotherapy (RT) in anal cancer: Preliminary results on toxicity and outcome
Authors: Glynne-Jones R. , Meadows H. , Wan S. 
Published: March 2020

14085 Background: Phase III trials have shown RT + 5-Fluorouracil (5-FU) + mitomycinC (MMC) as the standard treatment for patients with epidermoid anal carcinoma. The objective of this trial is to determine if capecitabine in combination with MMC has a similar outcome in terms of complete response (CR) rate and toxicity to a 5-day infusion of 5-FU. Capecitabine is a rational alternative to 5-FU as these cancers express high levels of thymidine phosphoralase. Methods: Main eligibility criteria are histologically proven anal carcinoma (epidermoid, squamous, basaloid), fit to receive capecitabine and MMC and ineligible for the ongoing phase III UK trial, ACT II. Exclusion criteria include complete local excision, prior chemoradiation, uncontrolled cardiovascular disease and known HIV+ve. All patients receive: 50.4Gy in 28F(RT) and capecitabine 1650mg/m2/day on each RT treatment day (M-F) over 6 weeks. In addition patients receive MMC 12mg/m2, day 1 only. Assessment of response is by CT scan at 4 wks post chemoradiation. Results: To date 18/30 patients have been registered. Pre-treatment characteristics are: median age 59 yrs (44–85); 7 male, 11 female; 13 Canal, 5 Margin; 5T1, 4T2, 6T3, 2T4, 1Tx; 4N+ve, 13N-ve, 1Nx. Data on 14 evaluable pts are presented here. RT compliance: 12 pts completed planned treatment, treatment was interrupted in 2 cases (chest pain 1; machine breakdown 1). Chemotherapy compliance: 10 pts completed protocol treatment, in 3 pts chemotherapy was affected due to toxicity (1 dose reduced, 2 stopped early 1 due to chest pain and 1 due to grade 3 skin and diarrhoea). One patient decided to stop treatment. Grade 3 toxicity was reported in 2 pts during treatment: dyspnoea 1, diarrhoea 1. Four weeks post chemoradition, 10 had CR, 3 had partial response and 1 pt was not assessable. Thirteen pts are alive and disease free at a median follow-up of 6 months (range 1 -13). One pt has relapsed in an inguinal node 9 months after the end of treatment following a previous CR. Conclusions: This early information suggests that this regimen can be given without interruption and with acceptable toxicity. The early response data is encouraging and the trial aims to reach target accrual by Summer 2006. Educational grant provided by Roche pharmaceuticals. [Table: see text]
Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree: series of 106 consecutive patients
Authors: Malaguti P. , Milella M. , Gelibter A. J. , Bossone G. , Sperduti I. , Ruggeri E. , Bria E. , Terzoli E. , Marolla P. , Cognetti F. 
Published: March 2020

14099 Background: Our group recently published a phase II trial of GEM infused at fixed dose-rate of 10 mg/m2/min over 100 min in patients with advanced PDAC and BTC. (Cancer September 15,2005). Given the promising results obtained in the first 40 pts, we expanded the cohort under an observational protocol and this is the report of such experience. Methods: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Results: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Conclusions: The results obtained with FDR-GEM in a series of 106 consecutive pts confirm previous results obtained in smaller series and suggest that pharmacokinetically rationale GEM scheduling may improve its therapeutic index. FDR-Gem may constitute a viable alternative to standard Gem infusion as first-line treatment in advanced PDAC and BTC. No significant financial relationships to disclose.
The retrospective analysis of single agent gemcitabine for biliary tract cancers
Authors: Kiba T. , Matsumoto S. , Hatano E. , Mori A. , Yasumi S. , Doi R. , Kitano T. , Ishiguro H. , Yanagihara K. , Teramukai S. , Fukushima M. 
Published: March 2020

14122 Background: At present, outcomes of advanced biliary tract cancers are dismal despite the prognosis of other many cancers are improving. Methods: We retrospectively analyzed survivals of 46 advanced biliary tract cancer patients, who were diagnosed between January 2001 and June 2005, and treated with gemcitabine 600–1,000 mg/m2 as an intravenous 30-min infusion on days 1, 8, and 15 for every 28 days, thereafter. Results: The median age was 63 (range 41–76) with 28 males and 18 females. Twenty-nine (63.0%) had no prior chemotherapy and 18 (30.4%) patients were inoperable cases. One (2.2%) achieved complete response; 5 (10.9%) achieved partial responses; 25 (54.3%) had stable diseases; 9 (19.6%) had progressive disease; and 6 (13.0%) were not evaluated for response. The median survival time and the 1 year-survival of all advanced biliary cancer patients were 8.6 months and 43.9%, respectively, those of the patients, who had the recurrence or residual cancer lesions after surgical resection were 13.5 months and 68.8%, and those of the inoperable patients were 5.4 months and 8.3%. Patients reported grade 3/4 neutropenia/leucopenia (4.3%) and grade 3 thrombocytopenia (2.2%). Grade 3 non-hematologic toxicities were general fatigue (4.3%) and renal failure (2.2%). Multivariate analysis demonstrated that history of surgical resection with tumor recurrence or with residual tumor was the independent predictors for survival. Moreover, except the features of the history of surgical resection, the prognosis of patients with low levels of serum albumin (< 3.7 g/dl) or ≥ 70 ages was worse than that of high levels of serum albumin (≥ 3.7 g/dl) or < 70 ages. Conclusions: In the treatment of biliary tract cancer, it seems that surgical resection even with possible residual tumor is beneficial for patients with good surgical candidate. The present study also suggests the possibility that the prognosis of patients with low levels of serum albumin (< 3.7 g/dl) or ≥ 70 ages might be worse than that of high levels of serum albumin (≥ 3.7 g/dl) or < 70 ages. No significant financial relationships to disclose.
Comparative proteome analysis of gonadal and extragonadal germ cell tumors
Authors: Honecker F. , Glaesener S. , Rohlfing T. , Brummendorf T. H. , Bokemeyer C. , Balabanov S. 
Published: March 2020

14530 Background: Germ cell tumors (GCTs) are the most common malignancy in young Caucasian males aged 20–40. Even though highly effective treatment strategies have been developed for the majority of patients (pts) with GCT, long term survival rate in pts with primary mediastinal non-seminomas nowadays remains below 50%. The molecular mechanism underlying the increased resistance to treatment remains elusive. Therefore, a systematic approach of global proteome analysis was used as a screening tool to compare GCT cell lines of gonadal and extragonadal origin. Methods: Comparative protein expression analysis of two GCT cell lines, NTERA2 (of gonadal origin) and NCCIT (of mediastinal origin) was performed using 2-dimensional gelelectrophoresis. Differentially expressed proteins were analyzed using matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF). Identification of proteins was performed using peptide mass-fingerprinting and NCBI/SwissProt database search. Results: On average, 761 spots on each gel were detected. Of these, 66 proteins were found to be differentially expressed in an at least in 2-fold manner. Expression of 47 proteins was found to be higher in NCCIT than in NTERA2, 19 proteins showed lower expression in NCCIT than in NTERA2. All 66 spots were analyzed, and 35 (51%) proteins were positively identified by peptid mass fingerprinting and database search. These proteins could be grouped into different categories: 9 are involved in metabolism, 5 each in protein folding and DNA-binding/transcription, 4 in cytoskeleton/cell movement, 3 in cell signaling/differentiation, and 1 each in ion transport and membrane/vesicle trafficking. Of 7 proteins, the function is currently unknown. Conclusions: This analysis demonstrates that proteomic tools are valuable in studying similarities and differences between gonadal and primary extragonadal GCTs. Further characterization and functional analysis of selected proteins is ongoing, with special emphasis on factors potentially involved in treatment resistance and sensitivity. Furthermore, the acquired proteome map of untreated cells will help to identify cellular changes occuring under different experimental conditions in vitro like induction of differentiation and response to cytotoxic treatment. No significant financial relationships to disclose.
High frequency of human leucocyte antigen (HLA) A2 and HLA-B7, -B44, -B15 and -DRB1–4 haplotypes in Swedish prostate cancer patients
Authors: Masucci G. V. , Andersson E. , Egevad L. , Kälkner K. , Harmenberg U. , Ryberg M. , Nilsson S. , Pisa P. 
Published: March 2020

14543 Background: Immune escape mechanisms depend on alterations in the expression of major histocompatibility complex (MHC) molecules and are known to play a crucial part in tumour development. We have previously presented high prevalence of the A2 allele in Scandinavia, which decreases with latitude in Europe and we noticed that prostate cancer mortality decreases among European countries in a similar way. We have furthermore characterized a group of prostate cancer patients with high frequency of HLA-A2 phenotype. Here we present prospectively the incidence of HLA-A2, homozygotes and haplotypes related to clinical parameters. Methods: Unbiased selected patients (n = 35) with localized prostate cancer, stage T1–3, NX-0, M0, eligible for curative full-dose radiotherapy, were analyzed for the genotypes HLA-A, -B, -C, and -DRB1 loci, by PCR/sequence-specific oligonucleotide hybridisation. Furthermore they have been compared to the frequencies of HLA alleles of healthy bone marrow donors in Sweden (based on 43 000 individuals). Results: The HLA-A2* phenotype frequency was 69% compared to the healthy Swedish population 58% (genotype frequency 39% vs. 35%). We also observed an increase in haplotypes compared to A2-B7 (14% vs 6%), A2-B44 (13% vs 6%), A2-B15 (14% vs 6%), A2-DRB1*04 (24% vs 8%). The ancestral haplotype HLA-A2, -B44, -DRB1*04 and HLA-A2, -B15, -DRB1*04 were expressed in 6% and 13% respectively in the patients group compared to the healthy Swedish population (2% and 3%). Conclusions: Our findings indicate that there is an unusual overrepresentation of the HLA-A2 allele and related haplotypes in prostate cancer patients. Further investigations are mandatory to establish if the negative prognostic correlation with HLA-A2 and the high frequent haplotypes is related to histological and clinical parameters as a result of disfunction of the immune system. No significant financial relationships to disclose.
A phase II trial to assess the activity of MVA5T4 plus interleukin-2 in patients (Pts) with metastatic renal cell carcinoma (MRCC)
Authors: Gary A. , Marsh L. , McDonald M. , Naylor S. , Harrop R. , Bernard D. , Amato R. J. 
Published: March 2020

14642 Background: MVA 5T4 consists of a highly attenuated vaccinia virus (modified Vaccinia Ankara, MVA) containing the human tumor associated antigen (TAA) 5T4. Greater than 90% of renal cell cancers are overexpressed by the 5T4 antigen. The primary purpose of this trial is to validate the hypothesis that, in this group of pts, it is possible to induce immune responses either humoral and/or cellular to 5T4 and to break tolerance to the antigen. The immune response will be correlated to clinical outcome. Methods: Eligibility included: pathologic diagnosis of confirmed clear cell or papillary cancer, progressive measurable MRCC, adequate organ/marrow function, Karnofsky Performance Status (KPS) ≥ 80%, any prior therapy, and no active CNS involvement. The dosage schedule of subcutaneous low dose IL-2 will be an initial dose 250,000 U/kg/dose for 5 days in week 1 followed by 125,000 U/kg/dose for 5 days each of weeks 2–6 inclusive. There will then be a 2 week recovery period before the next cycle commences. The dosage regimen of MVA 5T4 will be intramuscular injections given 14 days prior to the first cycle, day 0 and 1 injection given at the beginning of week 4 of the first cycle. In subsequent cycles, booster injections of MVA 5T4 will be given at week 1 only, prior to the commencement of subcutaneous IL-2 therapy. Results: 10 pts have been treated with MVA 5T4 and the LD IL2 regimen. The combination has been extremely well tolerated with no MVA 5T4 related events thus far. Although the study is still continuing to accrue, there are early signs of clinical responses in a number of patients receiving the combination. The immunological analysis is in progress. Conclusion: MVA 5T4 is well tolerated in this group of patients. The immune response will be presented along with clinical outcome. [Table: see text]
A multicentre, prospective phase 2 study of weekly schedule of carboplatin (C) plus paclitaxel (P) in first-line treatment of elderly patients (pts) with ovarian cancer (OC). The MITO (Multicentre Italian Trials in Ovarian cancer)-5 study
Authors: Zagonel V. , Ferrandina G. , De Vivo R. , De Matteis A. , Fabbrocini A. , Natale D. , Cavazzini G. , Scollo P. , Di Maio M. , Pignata S. 
Published: March 2020

15012 Background: CP every 3 weeks is the standard for pts with OC, but elderly pts frequently receive modified schedules or single agent chemotherapy to avoid toxicity. A prospective phase 2 study was conducted to describe tolerability and activity of a weekly schedule of CP in elderly pts with OC. Methods: Pts aged ≥70 years with chemo-naive OC, stage IC-IV, ECOG PS≤2 were eligible. Treatment was C (AUC 2) + P (60 mg/m2) on days 1, 8, 15 every 4 weeks, up to 6 cycles. A 2-stage minimax design was applied. With rate of pts without unacceptable toxicity in the first 3 cycles (UT) as primary endpoint, alpha 0.05 and beta 0.10, p0=0.75, p1=0.95, ≥23/26 pts without UT were required at the final stage. Toxicity was coded with NCI-CTC and response by RECIST. Geriatric assessment was performed by ADL (Activities of Daily Living) and IADL (Instrumental ADL). Results: 26 pts were enrolled. Median age was 77 (range 70–84). PS0: 10 pts, PS1: 16 pts. 14 pts (53.8%) had ≥2 comorbidities. 32%/72% had some ADL/ IADL dependency, respectively. 23 pts (88.5%) did not suffer UT. The 3 UT recorded were g3 heart rhythm (1 pt), g3 liver (1 pt), prolonged haematological toxicity (1 pt). Other main toxicities: g3 thrombocytopenia 1 pt, g2 constipation 2 pts (8%), g1 neuropathy 4 pts (15%). Out of 13 pts with at least one measurable lesion, 4 partial responses were observed (response rate 30.8%, 95% exact CI: 9.1–61.4). Out of 6 pts with non-measurable disease and 2 pts evaluable only for Ca125, 4 complete responses were observed (50%). Conclusions: In this series of elderly OC pts, characterized by a high incidence of comorbidities and functional impairment, weekly CP has a favourable toxicity profile. In this setting, a comparison of weekly vs 3-weekly CP is advisable to compare efficacy. No significant financial relationships to disclose.
Phase II trial of concomitant low dose temozolomide with external beam radiation (EBRT) followed by 12 months of temozolomide and irinotecan for newly diagnosed glioblastoma (GBM): Preliminary results of RTOG 04–20
Authors: Lieberman F. S. , Tsien C. , Berkey B. , Curran W. , Werner-Wasik M. , Smith R. , Grossheim L. , Hug E. , Mehta M. 
Published: March 2020

1510 Background: Irinotecan and temozolomide compare favorably to regimens tested in recurrent GBM. RTOG 04–20 intensifies the Stupp R, et al. (N Engl J Med. 2005 Mar 10;352(10):987–96) adjuvant regimen, using irinotecan and temozolomide in place of temozolomide alone. Methods: Adult patients with newly diagnosed histologically confirmed, supratentorial GBM were eligible. Subjects began temozolomide 75mg/m2 daily the night before initiation of EBRT, and continued until the final day of RT. Pneumocystis prophylaxis was begun prior to RT and for 2 weeks following RT. Within 6 wks after EBRT, subjects with stable or improved MRI were scheduled to receive temozolomide 150mg/m2 on days 1–5, and irinotecan 200mg/m2 on days 1 and 15 of 28 day cycles × 12. Clinical assessments and post contrast MRI are required prior to EBRT, after RT, and after every 2 treatment cycles. Only nonenzyme inducing anticonvulsants were allowed. Results: Accrual of 170 patients was completed in September 2005 with 140 patients currently evaluable. Median age is 57yr, 80% were RPA class III or IV. Prior to cycle 1 of adjuvant therapy, 32 subjects withdrew (20 progressed, 4 toxicity). Of the first 25 subjects receiving irinotecan, 10 suffered grade 3–4 hematologic toxicities in the initial 3 cycles. The protocol was modified by dose reducing irinotecan to 100mg/m2 in cycle 1, escalating to 150 and 200mg/2 in subsequent cycles only if no dose limiting hematologic toxicity occured. No data is yet available on patients who started adjuvant therapy at the lower dose of irinotecan. Diarrhea and constitutional symptoms are the most common nonhematologic toxicies Conclusions: Irinotecan 200mg/m2 days 1 and 15 with temozolomide 150mg/m2 days 1–5 of 28 day cycles was well tolerated treating recurrent GBM, but this regimen was too myelosuppressive when given after concomitant low dose temozolomide and EBRT. Primary outcome data should be available in late 2006. [Table: see text]