bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a phase I trial administering Zyflamend to subjects with high-grade prostatic intraepithelial neoplasia
Authors: Katz A. E. , Pierorazio P. M. , Masson P. , Goluboff E. T. , Stone B. A. , McKiernan J. M. , Benson M. C. , Olsson C. A. 
Published: March 2020

14575 Background: Subjects diagnosed with prostatic intraepithelial neoplasia (PIN) at prostate biopsy are at increased risk of developing prostate cancer on later biopsies. We initiated a phase I clinical trial to asses the safety and efficacy of the novel herbal anti-inflammatory, Zyflamend, to prevent prostate cancer in high-risk subjects with PIN. Methods: Men ages 40–75 diagnosed with high-grade PIN (without prostate cancer) on biopsy within the last six months were enrolled. Patients were assigned to one of eight treatment groups, with successive dose-escalation occurring in each group. Patients were evaluated every three months for 18 months; at which time they had a physical exam and blood samples drawn to monitor for toxicity, to check for fluctuations in PSA and testosterone, and monitor a battery of inflammatory serum. At 6, 12 and 18 months, 12-core transrectal ultrasound guided biopsy of the prostate was performed. Biopsy tissue was evaluated for the presence of PIN and/or prostate cancer then stained for inflammatory biomarkers. A NCI common terminology criteria for adverse events (v3.0) based questionnaire was used to monitor side effects. Endpoints are completion of the 18 month protocol without adenocarcinoma or diagnosis of adenocarcinoma prior to 18 months. Results: To date 25 patients have been enrolled; the expected closure date is March, 2006. The median patient age is 65.1 years with a median PSA level of 6.8. There have been no adverse events reported or toxicities apparent. Five patients (20%) have complained of grade I dyspepsia resolving spontaneously without intervention. Preliminary results include a total of 22 biopsies performed in 19 patients. 18 of the 22 biopsies were performed per protocol at scheduled visits, the remaining four were performed between scheduled visits. Of 22 biopsies completed seven returned positive for PIN (31.8%) and three have returned with adenocarcinoma (13.6%). Conclusions: The novel herbal anti-inflammatory, Zyflamend, appears to be associated with minimal toxicity and no serious adverse events when administered orally. Short term biopsy results indicate a low progression rate, although long-term efficacy awaits further studies. No significant financial relationships to disclose.
Treatment of advanced renal cell carcinoma with tumor lysate pulsed IL-12 secreting autologous dendritic cells
Authors: Wimpissinger T. F. , Felzmann T. , Hügel H. , Funovics P. , Stackl W. 
Published: March 2020

14585 Background: We have conducted a clinical phase I trial to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with advanced renal cell carcinoma (RCC). As opposed to previous cancer vaccination studies, dendritic cells were specifically enabled to secrete interleukin 12 (IL-12). Methods: Patients with advanced RCC (n = 11) received six weekly intranodal vaccinations with autologous monocyte-derived dendritic cells (mDCs). MDCs were loaded with autologous tumor cell lysate and were specifically stimulated to secrete IL-12 to polarize type-1 T-helper lymphocytes (Th1) and to directly present tumor antigens to cytotoxic T lymphocytes (CTL). Results: There was no significant treatment-related toxicity and no clinical evidence of autoimmunity. Vaccination was very well tolerated. Five patients had stable disease for at least five months, while four patients had progressive disease. Two patients with early clinically significant disease progression had to be excluded before completion of the treatment. In addition, we could detect enhanced anti-tumor immunity in vitro comparing immune response before versus after cancer vaccination. Conclusions: Our findings indicate that cancer vaccination with IL-12 secreting mDCs is well tolerated and has potential clinical and clear immunological effects in patients with advanced RCC. No significant financial relationships to disclose.
A phase I/II study of docetaxel in combination with doxorubicin HCI liposome injection in advanced androgen-independent prostate cancer
Authors: Martin M. E. , Ferguson L. A. , Williams D. A. , Laber D. A. 
Published: March 2020

14588 Background: There is no cure for men with AIPC. Recently two landmark studies demonstrated an improvement in survival for men with AIPC treated with docetaxel based chemotherapy. Doxorubicin is a very active agent against AIPC. Doxil is liposome-encapsulated doxorubicin with less toxicity. Methods: Objectives are to evaluate the efficacy and safety of DoxTax. A phase I dose escalation study was performed. Three cohorts according to the following dose escalation schedule were formed. In the absence of DLT, level 3 was the recommended dose for the phase II study. Response was assessed by size of measurable and non-measurable lesions (RECIST JNCI.2000), and PSA levels (JCO.1999). Toxicity was graded by the NCI CTCAE. Results: Eleven subjects with AIPC were enrolled and evaluated for toxicity and response. Total number of cycles administered: 59, median of 5.5 cycles/patient. Patient characteristics: Median age 67 years (53–81); prior hormonal manipulations 2 (1–2); prior chemotherapy 1 (0–2); ECOG performance status 1 (1–2); and median PSA 78 ng/ml (8.73–783). Objective response: Out of 11 subjects, four men (36%) achieved a reduction in PSA of > 50%, while one (9%) achieved a >80% PSA reduction, for an overall PSA response of 45%. Seven patients had measurable lesions. Using RECIST criteria, five of seven subjects maintained (SD). Palliative response: Nine subjects (82%) improved their ECOG performance status. Additionally, 8 men (73%) had decreased level of pain. Toxicity: No dose limiting toxicity occurred. One patient had grade 3 generalized weakness related to disease progression. Grade 1–2 adverse events were not related to the dose and included: 64% fatigue, 45% anemia, 18% neutropenia, alopecia, anorexia, vomiting, 9% each for nausea, thrombocytopenia, weakness, hand/foot, and neuropathy. Conclusions: DoxTax is a well-tolerated, easy to administer and effective therapy for patients with metastatic AIPC. Accrual to the phase II trial is ongoing. [Table: see text] [Table: see text]
Identification of urinary markers using proteomics analysis of urine in patients with bladder cancer
Authors: Nabi G. , Cash P. , N’Dow J. 
Published: March 2020

14605 Background: The discovery of new urinary markers for non-invasive detection and surveillance of bladder carcinoma remains an active field of current research with an aim to replace invasive investigations such as cystoscopy. We have analysed the urinary proteomes of patients with bladder tumor and compared them the urinary proteomes of a healthy volunteer control group to detect putative, tumour specific urinary markers for bladder tumor. Methods: 24 hour and midstream samples were collected from healthy volunteers and patients with newly diagnosed bladder tumours. Urinary proteins were isolated by a technique previously described by our group (Nabi G, N’Dow J, Hasan ST, Boot IR, Cash P. Proteomic analysis of urine in patients with intestinal segments transposed into the urinary tract. Proteomics. 2005 Apr;5(6):1729–33.)1. Proteins were resolved by 1-dimenional (1-DE) and two dimensional gel electrophoresis (2-DE). The proteins that differed when analysed by either 1-DE or 2-DE between patients and controls were identified using peptide mass mapping. Results: Six patients with newly diagnosed bladder cancer and 5 healthy volunteers were recruited into this study. All patients were found to have superficial transitional cell carcinoma with high grade (3 with grade 3, 3 with grade 2) on subsequent histopathological examination. For the same individual no detectable differences were observed in the protein profiles of midstream and 24 hour urinary samples when analysed by either 1DE or 2-DE. However, between patient and controls a number of proteins differed in abundance and these were identified. Proteins that were present in patients, but absent in controls, included FK506 binding protein 6 isoform, apolipoprotein A-IV, paraliprotein and lipid binding protein. Conclusions: The present study identified some of the novel urinary biomarkers in present with bladder cancer. Some of these have been shown to change their expression with deeper invasion of disease and might be useful in predicting behaviour of superficial bladder cancer. No significant financial relationships to disclose.
A randomised phase II trial assessing the impact of the addition of gefitinib to the combination of radiotherapy and short-term maximal androgen blockage in high-risk localised prostate cancer: Safety evaluation
Authors: Thirion P. 
Published: March 2020

14613 Background: Given the in-vitro evidence of potential increase in tumour radiosensitisation and hormonal deprivation-related tumour growth inhibiting effect by the addition of EGFR inhibitors, a randomised unblinded phase II trial was initiated to evaluate the impact of the addition of gefitinib to a combination of radiotherapy (RT) and maximal androgen blockage (MAB) in patients (pts) with high-risk localised prostate cancer. Methods: Eligible pts had biopsy proven localised prostate carcinoma Gleason score ≥7 and/or cT3 stage and/or initial PSA ≥ 20; without nodal and distant metastases. All pts were treated by 8 months MAB using LH-RH agonist (Zoladex 3.6 mg/month) and peripheral anti-androgen (Casodex 50 mg/day), and localised Conformal RT (Prostate + Seminal Vesicles, 75.6 Gy/42 daily fractions), initiated after 4 months of MAB. Pts were randomised to receive or not gefitinib 250 mg/day concomitantly for 8 months. The planned accrual was 98 pts. The end-points were ASTRO defined PSA-relapse-free survival at 18 months and toxicity. A safety evaluation was performed mid 2005. Results: 20 pts (10 per arm) were included from 10/2003 to 02/2005. No significant difference in RT or MAB-related toxicity was seen between the 2 arms. The addition of gefitinib significantly increased the frequency and intensity of reversible skin toxicity events (Rash-CTC grade 3–4: 4 pts Vs O pts, p = 0.04), with a trend for reversible transaminase enzymes elevation (TEE) (CTC grade 3–4: 2 pts Vs 0 pts). No treatment interruption was reported in the control arm. In the experimental arm, 3 pts completed treatment, 3 pts had a temporary (<10 days) gefitinib discontinuation (reversible asthenia and skin rash) and 4 pts had a permanent gefitinib discontinuation for reversible CTC grade 3 toxicity (skin rash: 2 pts, TEE: 2 pts). Conclusions: Gefitinib-related toxicity led to treatment discontinuation in 4 out of 10 patients. The trial is under review. This trial was supported by AstraZeneca. No significant financial relationships to disclose.
Preclinical and clinical investigation of histone deacetylase inhibitor valproic acid given orally in androgen independent prostate cancer
Authors: Sharma S. , Vogelzang N. , Wong B. , Adams C. , Manno P. , Welborne K. , Giraud Y. 
Published: March 2020

14614 Background: Considerable preclinical data suggests that histone deacetylase inhibitors (HDAIs) can cause differentiation and apoptosis of prostate cancer cell lines and inhibit prostate cancer xenografts in vivo. There is evidence that valproic acid (VPA) is a HDAI and can be administered safely to cancer patients intravenously (Atmaca et al J Clin Oncol 2004). Methods: In the current investigation, 6 cell lines of a variety of solid tumors including prostate cancers were treated with escalating concentrations of VPA (0.5, 1, 2 and 4 mM) over 24–144 hours. Cell growth inhibition was studied by a modified MTS assay. Simultaneously, patients with androgen independent prostate cancers were treated with dose escalations of oral VPA every week or as tolerated (10, 15, 20, 25 mg/kg). Weekly total and free serum VPA, PSA and serum testosterone levels were obtained. In addition, lymphocytes were collected for histone H3 acetylation. Results: VPA inhibited all solid tumor cell lines in a dose-dependent and time-dependent fashion. Optimal (>50% over control) inhibition of most cell lines required 2–4 mM exposure over at least 72–96 hours. Prostate and lung cancer lines were more sensitive to inhibition after VPA administration. A total of 5 patients (Median age 71, Range 48–78) were treated with VPA. Major adverse events included Gr 1 confusion (1 pt), Gr 1 fatigue (3 pts), Gr 1 Dizziness (2 patients) and Gr 1 nausea and vomiting (1 pt). When PSA levels were normalized for simultaneously drawn serum testosterone (Median 20, Range 16–281 ng/dl), all patients had transient drops in PSA. In 3 of 4 evaluable patients, normalized PSA increased after patients were discontinued from VPA because of side effects or co-morbid conditions. In 1 patient, normalized PSA declined after re-challenge with VPA. Conclusions: In this study, VPA has demonstrable activity in cell lines and in patients as measured by lowered PSA levels. Normalization of PSA to serum testosterone might be important to detect clinical effects of HDAIs. Updated clinical data and a correlation between PSA, serum levels of VPA and histone acetylation will be presented. No significant financial relationships to disclose.
Treg depletion with denileukin difititox (DD) enhances lymphocytosis and eosinphilia in patients treated with high-dose IL-2 (HDIL-2) for metastatic renal cell cancer (MRCC)
Authors: Gidron A. , Eklund J. , Mortone B. , Rademaker A. W. , Goolsby C. , Kuzel T. 
Published: March 2020

14627 Background: CD4+CD25+ T cells (Treg) play a suppressive role in immune regulation. DD is an IL-2 receptor specific cytotoxin. We postulated depletion of Treg with DD may enhance immune effector cell populations during HDIL-2 tx, including eosinophilia which was reported to be involved in immune response to neoplasm (Mattes et al. J Exp Med 197: 387, 2003). Methods: Seven pts (5 male, median age 58 yrs) with MRCC were tx’d with HDIL-2 and DD in different schedules to determine safety and effect on immune response as manifested by changes in Treg, lymphocyte, and peak eosinophil counts. Pts were tx’d with IL-2 600,000 IU/kg Q8H on days (d) 1–5 and 15–19. Three (group A) and 2 (group B) pts were given 6 and 9 ug/kg daily on d 8–10 respectively, while 2 (group C) pts received 9 ug/kg of DD on d -4- -2. Four (group D) pts with metastatic melanoma who received HDIL-2 as above but without DD were included as controls. Flow cytometry was done on days -4, 1,8,10,15 for group C and on days 1, 8, 10, 15, 22 for groups A, B, and D. CBC was obtained within 24 hours of flow cytometry. Results: After DD Treg increased in group A (mean change in absolute T-reg count of 16%) and decreased in groups B and C (34.5 and 20% respectively) compared to baseline. Group C trended toward a greater lymphocytosis at day 8 compared to all other groups (mean increase of 8.6 vs. 3.3 K/ul p = 0.059). A higher peak level of eosinophilia was noted in group C compared with groups A, B and D combined (mean increase of 9.9 vs. 3.0 k/ul p = 0.03). Group C demonstrated a higher mean % change in absolute number of CD8+ T-cells between onset of therapy and Day 8 compared to groups A, B, D combined (increase of 1095% vs. 496% respectively, p = 0.35). Toxicity was similar to that expected with HDIL-2. Conclusions: Administration of DD in conjunction with HDIL-2 was associated with a decrease in Treg that may be schedule and dose dependent. The results suggest an enhanced immune stimulatory effect as manifested by lymphocytosis and peak eosinophilia and CD8+ T-cells in group C. Despite small pt numbers, results suggest that pre-treatment with DD may confer an advantage. It is too early to know if laboratory results correlate to clinical benefit. [Table: see text]
Primary hormonal therapy for patients with localized or locally advanced prostate cancer
Authors: Shklar Z. , Rubinov R. , Steiner M. , Rabkin A. , Leviov M. , Keren S. , Sinatzky K. 
Published: March 2020

14630 Background: During 1998–2000, 68 patients with localized or locally advanced prostate carcinoma who were not suitable for radical therapy received primary hormonal therapy as the only treatment modality. The group consisted 15.8% of all prostate cancer patients referred to our center during the three years period. Methods: Their median age was 76.7 years (65–89). 42.4% had T1c disease, 30.3% T2a, 15.2% stage T2b and 12.1% T3. 78.4% had Gleason score 4–6, 10.8% Gleason 7 and 10.8% Gleason 8–10 prostate cancer. Median serum PSA level before starting therapy was 15.8 ng/ml (3.4–289). 76% received LHRH agonists monotherapy while 24% had complete androgen blockade. Patients were followed using repeated serum PSA level during 39–95 months (median 79.5). Results: 32/68 patients (47%) experienced PSA recurrence during the study period. Median time to PSA failure was 38.9 months (13–77). No clinical difference was observed between recurrent and non recurrent patients as regarding stage of disease or type of hormonal therapy. In relapsing patients high Gleason score (7–10) was more common (32.3% vs 11.6%) and median initial serum PSA value was higher (22.4 vs 14.5 ng/ml) than in the non recurrent group. During the study period, only 4/68 patients (5.9%) developed clinical disease, 10/68 patients (14.7%) died of unrelated causes and no patient died of prostate cancer. Conclusions: We conclude that primary hormonal therapy is a safe option for prostate cancer patients not suitable for more radical procedures. As expected, high Gleason score and higher initial serum PSA value are predictive for earlier relapse. No significant financial relationships to disclose.
Post-operative conformal radiotherapy on prostate cancer after radical prostatectomy. Results and dose constraint on bladder volume
Authors: Nakamura R. A. , Monti C. R. , Ferrigno R. , Trevisan F. A. , Castilho L. N. , Reinato J. A. 
Published: March 2020

14647 Background: To report on the results of post-operative conformal radiotherapy (3DCRT) on patients submitted to radical prostatectomy with high risk of biochemical failure or with biochemical failure. Methods: From July 1998 to December 2001, 40 patients with high risk of biochemical failure (T3 stage or positive margins) or with biochemical failure (PSA ≥ 0.2 ng/ml) after radical prostatectomy were submitted to 3DCRT on a single institution and were analyzed retrospectively. The median age was 65 years (52–74). The median pre-3DCRT PSA was 1.3 ng/ml (0–8.98). Twenty eight patients were submitted to pelvic 3DCRT. The median radiation dose on prostate region was 77 Gy (68.4–81). Biochemical failure was considered after 3 consecutive PSA increasing or the beginning of androgen suppression therapy for any reason after 3DCRT. Results: The median follow-up was 56.1 months (19.7–84.6). The 5-year actuarial biochemical progression-free survival was 84.5%. Six (15%) patients had biochemical failure and 4 (10%) distant metastases. The 5-year actuarial biochemical progression-free survival was 94.9% with pre-3DCRT PSA ≤1.5 ng/ml and 69.9% when >1.5 ng/ml (p = 0.0215). Two patients had rectal bleeding grade 2. Nine patients had urinary toxicity grade 2–3. The 5-year actuarial free from urinary toxicity grade 2–3 was 72.9%. Age >65 years and radiation dose >65 Gy on 30% of bladder volume resulted on more late urinary toxicity grade 2–3 (p = 0.0410 and p = 0.0177, respectively). Conclusions: 3DCRT was effective for biochemical control on patients with high risk of biochemical failure or with biochemical failure after radical prostatectomy. Patients with pre-3DCRT PSA ≤1.5 ng/ml have more biochemical control. It was suggested to restrict radiation dose ≤65 Gy on 30% of bladder volume to minimize late grade 2–3 urinary toxicity. More cautious on patients >65 years submitted to post-operative irradiation are required. No significant financial relationships to disclose.
Molecular profiles of prostate cancer versus today’s diagnostic tools
Authors: Vuaroqueaux V. , Diener P. , Eppenberger-Castori S. , Labuhn M. , Horica C. , Németh T. , Sulmoni M. , Fürstenberger G. , Eppenberger U. , Morant R. 
Published: March 2020

14659 Background: Tumor size, nodal status, the Gleason grading system and serum PSA values are today’s available prognostic tools of localized prostate cancer and the only help for adjuvant therapy. Based on the results of a feasibility study we continued the evaluation of the recently developed prognostic molecular signature. Methods: Of 60 CaP patients, who underwent primary prostatectomy in 2003 to 2005, fresh frozen samples of the tumor were asserved. The RNA extracted from cryocuts was tested. The quantitative RNA expression levels of 90 relevant genes involved in the different tumor hallmarks were simultaneously assessed. Results: Unsupervised agglomerative clustering of the obtained molecular profiles revealed different signatures. Correlations between these groups and the known TNM staging as well as Gleason scores were strongly present. Of interest was that all recurrences observed within this short period of time were found in a single cluster expressing higher levels of proliferation markers. Conclusions: The molecular profile of primary prostate cancer by quantitative RT-PCR is a powerful tool describing the biology of an individual tumor. Gene expression profiling can be precisely quantified and seems to be better reproducible than pathological judgments of the Gleason scores. Moreover, the gene panel is partially based on drug target genes and therefore of predictive value. Finally the method could be applied also in core biopsies. [Table: see text]
Recurrent epithelial ovarian cancer (EOC): What determines the outcome?
Authors: Kumanthem P. , Kumar L. , Janga D. , Hariprasad R. , Patnaik R. , Gupta A. , Kumar S. , Singh R. 
Published: March 2020

15003 Background: Recurrent EOC is a common clinical problem and treatment is not curative. We retrospectively analyzed the data on 354 patients with recurrent EOC to determine the impact of various prognostic factors on outcome. Methods: Between August, 1989 and June, 2005, 354 patients (median age 49 years, range, 28 to 80 years) were diagnosed as recurrent EOC. 259 patients received chemotherapy alone, 44 were treated with combination of secondary debulking surgery and chemotherapy or radiotherapy. Remaining 51 (14.4%) patients had no treatment. Main types of salvage chemotherapy included- cisplatin + cyclophosphamide (CP, n = 53), CP + adriamycin (CAP, n = 68), paclitaxel + carboplatin/cisplatin (TP, n = 78). 10 factors were analyzed for survival. Results: 56.5% of patients responded to chemotherapy; complete (CR)-34.2% and partial response (PR) in 22.3% of patients. 124 (35%) patients had no response or progressive disease. 10 (2.8%) died of chemo-toxicity and in remaining 20 status was not known. Median overall survival for patients who received treatment is 19 months vs 3 months for 51 patients who did not receive treatment, p < .001. Predictors of survival were - response to salvage chemotherapy (20 vs 8 months, p < .001), treatment-free interval (>6 months vs ≤ 6 months, 23 vs 9 months p < .001), site of relapse (single vs multiple, 22 vs 16 months, p < .001), Chemotherapy regimen (CP vs CAP vs Paclitaxel + carboplatin) p < .003 on univariate analysis. Age (≤50 years vs >50 years, p = 0.02), initial stage (I vs II vs III vs IV, p = 0.079), histology (serous vs others, p = 0.849), site of relapse (vault vs others, p = 0.156) were not significant predictors. On multivariate logistic regression analysis- response to salvage chemotherapy (HR 0.21, 95% CI 0.15–0.30), treatment-free interval (HR 0.36, 95% CI, 0.20–0.64), and site of relapse (vault vs others, HR 1.22, 95% CI 0.78–1.94) attained significance among 10 factors analyzed. Conclusions: Present study confirms that all patients with recurrent EOC should receive treatment. Response to salvage chemotherapy, a longer treatment-free interval (>6 months) and single site of metastasis are predictors of significantly superior outcome. No significant financial relationships to disclose.