bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of weekly docetaxel for second-line treatment of urothelial carcinoma.
Authors: Kim Young Saing , Choi Moon Ki , Hong Jung Yong , Maeng Chi Hoon , Lee Soonil , Hwang In Gyu , Lee Sang-Cheol , Sun Jong-Mu , Park Se Hoon , Lee Jeeyun , Lim Ho Yeong 
Published: March 2020

e15613 Background: Despite high response rates (RRs) with first-line platinum-based chemotherapy in advanced urothelial carcinoma (UCC), treatment after first-line failure remains unclear. The present multi-center phase II trial evaluated the tolerability and efficacy of weekly docetaxel as second-line chemotherapy for UCC. Methods: Between Aug 2010 and Sep 2012, 31 patients with measurable UCC, progressive after one prior platinum-based chemotherapy for advanced disease, were treated with docetaxel 30 mg/m2 on days 1 and 8. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The primary endpoints were the RR, progression-free survival (PFS), and safety. To detect a 20% difference in RR (6% vs. 26%), 28 eligible patients were required. Results: All 31 patients were previously treated with gemcitabine/platinum and had Bellmunt risk of one or more. The patients’ median age was 64 years (range, 40 to 79) and 31 (100%) patients had an ECOG performance status of 1. A total of 106 (median, 2; range, 1 to 16) chemotherapy cycles were delivered. Although fatigue (13%) and anorexia (6%) were the most frequently observed grade 3 or 4 toxicities, safety profiles were generally mild and manageable. One patient developed prolonged thrombocytopenia which led to treatment discontinuation but was resolved thereafter. In an intent-to-treat analysis, two (6%) patients achieved objective response, which maintained for 3.0 to 7.8 months. Eight patients experienced disease stabilization, resulting in a disease control rate of 32%. The median PFS and overall survival were 1.4 (95% CI, 1.3 to 1.6) and 9.6 (95% CI, 7.8 to 11.4) months, respectively. Conclusions: Second-line chemotherapy with weekly docetaxel was well tolerated but demonstrated modest antitumor activity in patient with advanced UCC who had progression after first-line platinum-containing regimen and poor prognostic factors. Clinical trial information: NCT01711112.
Lymphopenia and clinical outcome of elderly patients treated with sunitinib for metastatic renal cell cancer.
Authors: De Giorgi Ugo , Rihawi Karim , Aieta Michele , Lo Re Giovanni , Sava Teodoro , Masini Cristina , Baldazzi Valentina , De Vincenzo Fabio , Camerini Andrea , Fornarini Giuseppe , Burattini Luciano , Rosti Giovanni , Moscetti Luca I. , Chiuri Vincenzo Emanuele , Luzi Fedeli Stefano , Ferrari Vittorio D. , Amadori Dino , Basso Umberto 
Published: March 2020

e15615 Background: Lymphopenia is associated with toxicity and outcome in several cancer types. We assessed the association of pre-treatment lymphopenia with toxicity and clinical outcome of elderly patients with metastatic renal cell cancer treated with first-line sunitinib. We evaluated the prognostic factors in these patients. Methods: We reviewed the clinical files of 181 patients aged >70 years with mRCC treated with first-line sunitinib in seventeen Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts <1,000/µL. Results: Twenty–nine patients (16.0%) had a baseline lymphocyte counts <1,000/µL, and 152 (84%) ≥1,000/µL. No difference between the two groups was reported in overall response rate (p = 0.207), dose reductions (p = 0.740); discontinuations due to adverse events (p = 0.175), overall incidence of grade 3-4 toxicities (p = 0.112) even if more patients in the group with lymphopenia had grade 3-4 neutropenia (p = 0.017), grade 3-4 thrombocytopenia (p = 0.017) and grade 3-4 diarrhea (p = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (p = 0.015 and p = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (p = 0.007, p < 0.0001 and p = 0.023, respectively). Conclusions: Sunitinib appeared safe and active in elderly patients with lymphopenia. Lymphocyte counts is an independent prognostic factor for OS in elderly patients with mRCC treated with first-line sunitinib.
Vinflunine (VFL) as second-line chemotherapy for patients with transitional cell carcinoma of the urothelium (TCCU): A multicenter retrospective study.
Authors: De Velasco Guillermo , Chirivella Isabel , Gonzalez-Grajera Belen , Fernandez Calvo Ovidio , Pinto Alvaro , Mohedano Nicolas , Santander Carmen , Castellano Daniel E. 
Published: March 2020

e15620 Background: VFL is the standard chemotherapy in second-line advanced TCCU in Europe (EMA approval 21/09/2009). We set up a multicenter retrospective study to evaluate the efficacy and toxicity of VFL in patients (pts) with advanced TCCU after platinum failure within the framework of routine practice. Methods: Descriptive and retrospective study in pts who had demonstrated prior progression to a platinum-containing chemotherapy regimen at 7 centers. VFL standard dose (280-320/m2 every three weeks) was administered until progression or unacceptable toxicity. Objective response was evaluated according to RECIST criteria v.1.1. Results: Between April 2010 and December 2012, a total of 45 pts with median age of 68 years (range 47-83) were analyzed. Main characteristics: ECOG 0-1-2 in 7pts (15.6%), 33pts (73.3%), 5pts (11.1%). Mean creatinine clearance was 59 ml/min. Primary sites of disease were bladder 39pts (86.7%), renal pelvis 5pts (11.1%) and prostatic urethra 1pt (2.2%). All pts had previously received platinum-based chemotherapy as a first-line treatment (cisplatin in 45% of pts). Metastatic locations were: 27pts (60%) lymph nodes, 18pts (40%) lung, 13pts (29%) bone and 10pts (22%) liver. The median number of cycles of VFL was 5 (1-18). All pts were assessed for response, one (2.2%) patient presented complete response (CR), 11pts (24.4%) partial response (PR), 18pts (40%) stable disease (SD) and 15pts (33.4%) progressive disease (PD). Median progression-free survival was 4 months (95% CI, 2.2-5.7). Median overall survival (OS) was 11 months (95% CI, 3.5-18). OS at 6 months was 45%. Liver metastasis was the main prognostic factor for OS (p=0.04). Grade 3/4 adverse events included neutropenia 6pts (13%), constipation 4pts (9%), abdominal pain 4pts (9%) and nausea/vomiting 3pts (6%). Conclusions: This retrospective analysis confirm VFL as an active agent in pts progressing after platinum-based combination for advanced TCCU in a daily clinical practice in Spain. As ESMO (Bellmunt J, 2011) and Spanish (Castellano D, 2012) guidelines recommend vinflunine, it should be offered in this setting or alternatively, treatment within a clinical trial.
Hand-foot syndrome (HFS) and asthenia/fatigue (A/F) as biomarkers of sunitinib efficacy in Chinese patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Qin Shukui , Jin Jie , Guo Jun , Wang Jin-Wan , Zhou Fang-Jian , Huang Yi-Ran , Ren Xiu-Bao , Ye Ding-Wei , Pan Sharon , Sajben Peter , Wang Qiao 
Published: March 2020

e15622 Background: In an open-label phase IV study of sunitinib as 1st-line treatment (Tx) in Chinese pts with mRCC, median progression-free survival (PFS) and overall survival (OS) were 61.7 and 133.4 wk, respectively; objective response rate (ORR) was 31.1% (Ann Oncol 2012;23:851P). We retrospectively investigated correlations between on-Tx HFS or A/F and efficacy endpoints in pts from this trial. Methods: AEs were recorded and graded using NCI CTCAE v3. Median PFS and OS were estimated by Kaplan−Meier method. The log-rank test was used to compare PFS and OS between groups with and without HFS or A/F. Fisher’s exact test was used for ORR. Multivariate and time-dependent covariate analyses were conducted to assess the influence of various prognostic factors on the association between AEs and efficacy and to address potential bias from longer drug exposure, respectively. Landmark analyses were used to compare outcomes in pts with and without HFS or A/F after 6 and 12 wk of Tx. Results: Of 103 pts included in the analyses, 67 (65%) and 54 (52%) had on-Tx HFS and A/F, respectively. Pts with HFS had greater ORR and significantly longer PFS and OS than pts without HFS (Table). Pts with A/F had greater ORR and longer PFS and OS than pts without A/F. By multivariate analysis, HFS was a significant predictor for both PFS and OS, and A/F was a significant predictor for PFS (Table). However, no findings were significant in the time-dependent covariate (Table) or landmark analyses (not shown). Conclusions: The development of HFS or A/F at any time during Tx with sunitinib was significantly associated with better outcome; however, time-dependent covariate and landmark analyses suggest that these AEs may not be reliable predictors of efficacy at early time points. Clinical trial information: NCT00706706. [Table: see text]
Options and limitations using 11c-acetate PET/CT imaging for detection of recurrent disease following radical prostatectomy in patients with prostate cancer.
Authors: Mueller-Mattheis Volker , Fahlbusch Melanie , Hautzel Hubertus , Albers Peter 
Published: March 2020

e16003 Background: Patients with rising PSA levels after definitive local therapy of prostate carcinoma often present a diagnostic dilemma . A local recurrence or metastatic lymph node lesions would be amenable to additional local therapy. In this prospective study the effectiveness of 11C-acetate PET (AC-PET) matched with corresponding CT scans in patients with PSA relapse were evaluated. Methods: 103 patients (mean age 70.87 years; range 56 – 90 years) with histologically confirmed adenocarcinoma of the prostate were enrolled in this study because of rising PSA values following RP (n = 97) or radiotherapy (n=6). Whole-body PET images were obtained after iv - administration of 1,000 MBq of 11C-acetate. A CT scan from the neck to the pelvic floor was performed additionally. An image overlay of corresponding CT and PET scans was done. By using attenuation corrected PET data, standardized uptake value (SUV) was calculated, cut-off 2. Results: Out of 103 patients n=42 were AC-PET positive. PSA level in 16 of this subset was between 0.5 and 1.45 ng/mL (mean value 1.14 ng/mL), in 16 patients between 2.7 and 9.01 ng/mL, and 7 patients had a PSA distribution between 13.4 and 30.5 ng/mL, respectively. Analysing the AC-PET positive patients, in 16/42 AC-PET demonstrated hypermetabolic lymphnode lesions, in 10/16 metastatic lesions were histopathologically confirmed, in the remaining 6 unspecific inflammatory tissue alterations were identified. In 9 patients with corresponding AC-PET and CT scans radiotherapy of proven lymphnode metastases was performed followed by decreasing PSA level. 23/42 patients were treated with hormone manipulation (21/23) or chemotherapy (2/23). Combining the patients having undergone surgery and radiotherapy (n=25) there were 19/25 true positive in terms of AC-PET, in 13 / 25 PSA level was < 2.0 ng/mL. Conclusions: Although AC-PET seems to be a promising tool in the detection of recurrent prostate cancer even with PSA levels < 2 ng/ml, false positive patients with a different metabolism marked by 11C-acetate decrease the specificity of the approach. Thus there is still a need for a more specific tracer development.
A pilot study comparing circulation tumor cells (CTC) detection by AdnaTest prostate assay to CellSearch in patients (pts) with castration resistant prostate cancer (CRPC).
Authors: Samoila Aliaksandra , Bastos Diogo Assed , Herkal Amrita , Patel Chintan , Curtis Kristen Rebecca , Schreiber Nicole A , Anand Aseem , Fleisher Martin , Scher Howard I. , Danila Daniel Costin 
Published: March 2020

e16005 Background: The detection of CTC in blood is prognostic for survival in CRPC. CellSearch is an FDA cleared CTC enumeration assays that reports the number of cells meeting strict morphologic and immunohistochemical criteria. An unmet need is to increase detection rates in pts with favorable < 4 cells/7.5 ml of blood. Here we studied CTC detection using AdnaTest PCR based assay in relation to CellSearch. Methods: Whole blood was collected under an IRB approved protocol from 40 pts with CRPC for the AdnaTest and CellSearch assays. The standard CellSearch platform was used for CTC detection. The AdnaTest includes immunomagnetic cell enrichment using EpCAM and Her2 antibodies followed by mRNA isolation and multiplex PCR amplification of 3 prostate associated transcripts (PSMA, PSA and EGFR). The measurement of one or more transcripts above 0.1ng/µl is considered a positive test. Results: CellSearch CTC counts and AdnaTest detection rates are presented in the Table. Overall AdnaTest detected CTC in 26 pts (65%, 95% CI 50-80%), including 6 of the 18 (33%, 95% CI 11-55%) pts with no CTC using CellSearch. Of 23 pts with ≤ 4 CTC by CellSearch, 10 pts (45%, 95% 30-61%) were positive by AdnaTest. In contrast, in 17 pts with ≥ 5 CTC by CellSearch, 16 pts (94%. 95% 87-100%) were positive by AdnaTest. Overall, 70% (28) of the 40 pts had detectable CTC by either AdnaTest or CellSearch, with positive agreement in 71%. AdnaTest positivity was based on detection of PSA, alone or in combination with PSMA or EGFR. Only 1 patient (4%) was positive for EGFR alone, and none by PSMA alone. Conclusions: AdnaTest demonstrated incremental detection of CTC in pts with no CTC identified by CellSearch. This is consistent with the difference between PCR detection vs the strict definition of CTC using CellSearch, which is known to represent only a small proportion of the EpCAM+ events in the chamber. Further studies to assess the utility of this assay as a biomarker for clinical outcome in pts with CPRP are warranted. [Table: see text]
Docetaxel and curcuminoids (CCM) combination in patients with castration-resistant prostate cancer (CRPC): A phase II study.
Authors: Mahammedi Hakim , Pouget Mélanie , Planchat Eloise , Cure Herve , Durando Xavier , Bayet-Robert Mathilde , Van-Praagh Isabelle , Atger Marc , Guy Laurent , Abrial Catherine , Chollet Philippe J. M. , Eymard Jean-Christophe 
Published: March 2020

e16021 Background: Prostate cancer is a major problem in the aging male population. Docetaxel, the first-line reference treatment in CRPC induces a prostate-specific antigen (PSA) response in 45% of patients and an objective tumor response in 12%. Preclinical studies suggested that curcuminoids inhibit tumor metastasis, invasion and angiogenesis and reverse drug resistance. We wanted to potentiate docetaxel by curcuminoïds in CRPC first line. Our previous phase I study showed the safety and the tolerability of CCM associated to docetaxel for advanced breast cancers. We have conducted in 2009-2010 a phase II study to assess the response of CRPC to this combination. Methods: Patients (n=30) with progressing CRPC and rising PSA were enrolled to receive the experimental treatment. Docetaxel was given in standard conditions (75mg/m², 1h i.v infusion every 3 weeks for 6 cycles + prednisolone) with CCM orally at the dose of 6gr/day (7 days by cycle: d-4 to d+2). The primary endpoint was response rate assessed by biological and paraclinical examinations. The secondary endpoints included safety, time to progression and compliance. Twenty nine patients were evaluable on PSA assessment and 15 on RECIST criteria. Results: 26 patients received the treatment totality and 4 withdrew prematurely. No patient withdrew for toxicity (2 deaths and 2 PSA progressions). A PSA response was observed in 17/29 patients (59%) (4 complete and 13 partial) observed rapidly (before the 3rd cycle) for 15 patients. The median time to subsequent PSA progression (TTP) was 5.8 months. Six patients (40%) had a partial objective response and 9 (60%) a stable disease. The median TTP on targets was 7.85 months (n=13/15). The regimen was well tolerated, with uncommon grade 3/4 toxicity; no adverse event was attributed to CCM. Of 169 cycles, 150 (89%) were completed with perfect compliance. Overall survival was 19 months (mean) and 24 months (median) with 17 events as of december 2012. Conclusions: These results are promising in improving the response rate to docetaxel in terms of both PSA decrease and objective response, with good tolerability and acceptability of CCM. A randomized trial is necessary to confirm this results. Clinical trial information: NCT01012141.
The economic burden of metastatic castration-resistant prostate cancer: U.S. Medicare perspective.
Authors: Eapen Sara , Andrews Ryan M. , Gorin Brian , Higano Celestia S. 
Published: March 2020

e16025 Background: Castration-resistant metastatic prostate cancer (mCRPC) is associated with high medical costs and resource utilization. The aim of this study was to examine the total direct medical costs and resource utilization of mCRPC patients covered by Medicare. Methods: A retrospective analysis was performed using a representative 5% sample of 1999-2010 quarterly Medicare claims. Males over the age of 18 were included in the analysis if they had all of the following: (i) at least one claim with a diagnosis of prostate cancer, (ii) at least one claim for a mCRPC treatment between January 1, 1999 and December 31, 2010, (iii) a diagnosis of bone metastases after their prostate cancer diagnosis but before receiving mCRPC treatment, (iv) at least one quarter of Medicare eligibility before and after their index quarter, which was defined as the quarter of bone metastases diagnosis. Descriptive summary statistics of patient healthcare resource utilization and medical costs were reported on a per patient per quarter (PPPQ) basis. Results: A total of 5,018 mCRPC patients were identified from 1999-2010 with a mean (SD) age at index of approximately 76 (7) years and an average follow up time of 2.0 years. During the index quarter, mCRPC patients had a mean (SD) of 29.2 (19.1) medical claims for a mean (SD) cost of $13,649 ($15,943). Post index, the average number of claims per patient was higher than pre-index (20.0 vs. 9.8) resulting in substantially higher costs ($9,512 vs. $3,220). MCRPC patients received more frequent medical scanning during and after index, with patients receiving 3.2 scans during the index quarter and 1.2 scans PPPQ post-index compared to 0.6 scans PPPQ pre-index. PSA testing increased from 0.6 tests PPPQ before the index quarter to 1.4 tests PPPQ from the index quarter onwards. Conclusions: Based on data from the Medicare database from the decade prior to the approval of sipuleucel-T, cabazitaxel, abiraterone, and enzalutamide , the cost of care of patients with mCRPC was approximately $76,000 over 2 years. However, since the Medicare database does not include outpatient prescription data, the actual cost over 2 years is an underestimate. Future costs are expected to rise with the availability of these new agents.
International comparison of androgen-deprivation therapy (ADT) for the treatment of nonmetastatic (M0) prostate cancer (PC).
Authors: Hope Kirsty , Graham Alex , Arellano Jorge , Liede Alexander 
Published: March 2020

e16040 Background: ADT represents standard of care for PC patients (pts) with signs of recurrence after primary therapy (tx). Nature and extent of ADT among M0 pts is not well-characterized, and nearly all ADT-treated pts relapse to develop castration-resistant PC (CRPC) after a median 18-24 months (mos) (Felici 2012). This physician survey quantifies ADT in populations with high or increasing incidence of M0 PC (Ferlay 2010). Methods: A 45-minute online survey was completed by urology and oncology practitioners (MDs) from 19 countries. Eligibility ensured MDs were responsible for tx decisions in the care of M0 PC, and had ≥10 pts on ADT. MDs were asked about tx at different points in the PC pathway, focusing on ADT (gonadotropin-releasing hormone [GnRH] or bilateral orchiectomy [bil orch]), type and duration of GnRH (intermittent vs. continuous), concurrent tx, and pts with CRPC (high risk CRPC definitions explored). Results: In total, 441 MDs completed the survey; predominantly urologists (88%). MDs had 98,689 PC pts under their care, 76,386 (77%) M0 PC. Of M0 PC, 38% received ADT: 37% (28104) GnRH (mainly leuprorelin [47%] or goserelin [21%]) and 1.6% (1251) bil orch (Table). The 34% tx rate reported by US MDs is consistent with decreasing ADT use (Shahinian 2010), whereas rates remain higher in Europe, particularly for Eastern European pts. Across regions, 74% (20,729) of GnRH pts received ≥6 mos, 48% (13,594) continuously; of these, 71% were expected to develop CRPC, 57% of CRPC were considered high risk for bone metastasis (BM). PSA doubling time ≤6 mos was most commonly cited high risk definition. Conclusions: These findings further our understanding of ADT use among M0 PC, which differs by country, by region, with highest rates reported in Europe. ADT rates have public health implications on the number of men expected to develop CRPC and be at high risk of BM in the future. [Table: see text]
Anti-androgen resistance in prostate cancer cells induced by IL-1β.
Authors: Zhu Xinhua , Staverosky Julia , Logan Susan 
Published: March 2020

e16057 Background: Chronic inflammation has been linked to cancer initiation and progression in a variety of tissues. The impact of acute and chronic inflammatory signaling on androgen receptor (AR) function has not been widely studied. We employed IL-1β, one of important cytokines responsible for inflammation to treat LNCaP, which is both androgen- and bicalutamide-sensitive prostate cells. Methods: To mimic the effects of inflammation on AR function, we treated the LNCaP prostate cancer cell line either acutely or chronically with IL-1β. AR protein and mRNA expression levels were examined over time course of IL-1β stimulation in either the presence or absence of the synthetic androgen, R1881. The population of cells chronically treated with IL-1β are called LNCaP-CI. Chromatin immunoprecipitation was used to measure the active epigenetic marks H3K4 dimethylation on the enhancer of M phase genes such as CDC20, CDK1 and UBE2C. mRNA level of AR, CDC20, CDK1 and UBE2C was done with quantitative PCR. Results: Acute IL-1β treatment inhibits the transcription of the AR gene itself, resulting in the reduction of AR protein levels. In cells subjected to chronic IL-1β stimulation, the transcription of the AR gene is restored within a few cell passages, and the cells acquire the ability to grow in the presence of the anti-androgen, bicalutamide. Using chromatin immunoprecipitation, we found that acquired bicalutamide resistance in chronic IL-1β treatment correlates with increased selective active epigenetic mark H3K4me2 occupancy on the M-phase gene enhancer of UBE2C, CDC20 and CDK1 through AR recruitment and subsequent up-regulation of the M-phase genesin LNCaP-CI cells. Conclusions: Bicalutamide resistance induced by IL-1β recapitulates the biological properties of LNCaP-abl (CRPC cells) and CRPC clinical cases through upregulation of M-phase genes, suggesting that chronic inflammation, induced by IL-1β characterizes the development of CRPC from androgen-dependent prostate cancer transformation. The data will lead to further investigation of identifying potential therapeutic targets in IL-1β pathway to prevent the process of this lethal transformation.