bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Chemotherapy in hormone-refractory prostate cancer: Docetaxel with and without VT122.
Authors: Bhattacharyya Gouri Shankar , Bascomb Newell , Malhotra Hemant , Biswas Ghanashyam , Bondarde Shailesh Arjun
Published: March 2020

e16062

Background: Randomized study in metastatic castration resistant prostate cancer treated with docetaxel and the benefit of adding VT122. Methods: Castration resistant prostate cancer with bone metastasis, symptomatic were treated with docetaxel 75 mg/m2 every 3 week and prednisolone with continued androgen suppression, LHRH analogue and zoledronic acid, every 28 days with or without VT122. VT122 is a drug combination of etodolac, a COX-2 inhibitor and propranolol, a beta blocker with anti angiogenic properties; this combination has previously been shown to be anti cachectic, anti neoplastic.The dose of etodolac was titrated by C-reactive protein levels to a maximum of 800 mg/day. The dose of propranolol was titrated to keep heart rate at around 60 b/min to 70 b/min. GCSF was allowed, all patients were given Calcium and VitaminD. The primary end point was time to progression, a composite end point of objective progression by RECIST criteria, PSA progression or pain progression, whichever occurred first was applied.The McGill questionnaire was applied to patients. Number of patients 69; 34 in docetaxel arm; 35 in VT122 arm. Age between 50-65 years. Taken from 3 centers with PS ECOG <2 controlled comorbidity with stable analgesic regime. All patients were planned for 6 cycles of docetaxel. Follow-up was for a period of two years. Results: Median age of 62 years with ECOG status 1 was seen in 88%. The median PSA value was seen as 138 ng/ml (10 - 600). 66% in both arms had measurable disease. Conclusions: Addition of VT122 improves response rates, duration of response and symptom scales along with 1-year survival which are statistically significant; toxicities are also significantly decreased and indicating increased efficacy and safety profile of docetaxel. The efficacy and control of toxicity and easy to administer makes this an attractive combination. [Table: see text]
Effectiveness of abiraterone as salvage therapy in patients with docetaxel- and castration-resistant prostate cancer (mDCPC) that progressed during second-line chemotherapy with carboplatin plus weekly docetaxel (DC).
Authors: Morgan Michael A. , Fenner Martin , Grünwald Viktor , Merseburger Axel S. , Ganser Arnold , Reuter Christoph W.
Published: March 2020

e16064

Background: Our recent data have shown that carboplatin AUC5 on d1 plus docetaxel at a dose of 35 mg/m2 iv on d1, 8, 15 every 4 weeks (q4w) is an effective salvage therapy in mDRPC. Patients (pts) who have progressive disease during DC treatment survive only ~7 months and many are symptomatic. We have demonstrated that high free testosterone (FT) serum levels during DC treatment have a negative prognostic value for PSA response and overall survival in these pts. In this study the impact of abiraterone treatment and other subsequent salvage regimens after DC failure was analyzed. Methods: DC failure was defined as disease progression during DC treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC pts were treated with at least 2 cycles DC until disease progression. At the time of the current analysis 69 pts have progressed and 43 pts received one or more subsequent therapies (1-3). Results: Overall survival (OS) of all 69 pts who have progressed during DC treatment was 8.0 months (CI 95% 3.7, 12.3). 43 pts received subsequent salvage therapies including mitoxantrone-prednisone-etoposide (MPE) (n=10), cabazitaxel (n=13), docetaxel-oxaliplatin (n=8), abiraterone (n=15), enzalutamide (n=5) and doxorubicin-ketokonazol (n=5). OS of these 43 pts was 14.6 months (CI 95% 11.0, 18.2).In pts receiving abiraterone as salvage treatment, OS after DC was 21.8 months versus 11.9 months (CI 95% 9.0, 14.8) in pts receiving other regimens (HR 0.17, CI 95% 0.07, 0.42; p<0.001). Responses of prostate-specific antigen (PSAR; ≥30% and ≥50%) were only frequently observed in pts receiving abiraterone (8/15, 53.3% and 4/15, 26.7%, respectively). Conclusions: Our data demonstrate for the first time that testosterone is an important prognostic factor for PSA response and OS in mDRPC patients receiving DC chemotherapy and that targeting testosterone after DC failure prolongs post-DC survival.
Predictors of clinical metastases and survival among nonmetastatic prostate cancer (PC) patients (pts) treated with androgen-deprivation therapy (ADT) in Sweden.
Authors: Hernandez Rohini Khorana , Mesterton Johan , Banefelt Jonas , Stålhammar Jan , Sobocki Patrik , Persson Bo-Eric , Liede Alexander
Published: March 2020

e16066

Background: ADT is the standard of care in Sweden for PC pts with signs of recurrence after primary therapy (tx). Studies of predictors of metastasis (mets) and survival have largely focused on pt characteristics at cancer diagnosis. Time-varying factors, such as prostate-specific antigen (PSA) levels, may have greater impact on a pt’s risk of disease progression. This study examines predictors of mets and survival among men with PC treated with ADT. Methods: Using electronic medical records from Swedish urology clinics linked to national registries (Cancer Registry, National Pt Registry, Cause of Death Registry), we identified men with PC and no evidence of mets treated with ≥6 months (mos) ADT (gonadotropin-releasing hormone agonists/antagonists or bilateral orchiectomy) between 2000-2010 with ≥2 PSA values. Men were followed from ADT index date to mets, death, or end of follow-up (12/31/2010). Multivariate competing risks regression analysis was used to estimate hazard ratios (HR) and 95% CIs; predictors and covariates of interest included PC diagnosis year (yr), age, comorbidities, anti-androgen tx, region, and time-varying characteristics (PSA absolute value, PSA doubling time [DT]). Results: Cohort was 446 men with mean follow-up of 3.3 yrs. Most mets were to the bone (7-yr cumulative incidence 25% for bone, 30% for any mets). Median survival was 6 yrs (5.9 mos after bone mets, 6.1 mos after any mets). Higher PSA and shorter PSA DT were strong predictors of all outcomes. In particular, PSA DT ≤ 6 mos was associated with increased risk of bone mets (13.9 [8.0 – 24.1]), any mets (7.9 [4.9 – 12.8]), mortality (5.7 [3.9 – 8.5]), and bone mets-free survival (6.9 [4.7–10.1]) when compared to PSA DT > 6 mos. HRs were adjusted for age, Charlson comorbidity index, anti-androgen tx, and region. Conclusions: PC pts treated with ADT are at significant risk of bone mets, any mets, and death. This study based on real-world data demonstrates the importance of PSA measured after ADT initiation in defining high risk of these outcomes, particularly PSA DT ≤6 mos. PC pts may benefit from new tx to prevent disease progression since survival is short after bone or other mets.
Health-related quality of life after IMRT or IMRT+ HDR brachytherapy for intermediate or high-risk prostate cancer: Five-year results of a prospective trial.
Authors: Guix Benjamin , Lacorte Teresa Maria , Bartrina Jose Maria , Tello Jose Ignacio , Guix Ines , Galdon Guillermo , Espino Marc , Guix Teresa
Published: March 2020

e16071

Background: To report long term Health Related Quality of Life (HRQoL) in a prospective series of 629 patients with intermediate or high-risk clinically localized prostate cancer treated with either IMRT or IMRT + HDR. Methods: Between December 1999 and December 2010, 629 patients (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-3D-IMRT to the prostate in 38 fractions (group 1; 315 patients) or 46 Gy LD-3D-CRT+ 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 316 patients), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumors’ characteristics. Toxicities were scored by the EORTC /RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels as well as HRQOL was done. Results: All pts completed treatment. None pts included in group 1 or 2 had grade 3 or more rectal toxicity. With a mean follow-up of 96 m, the 8-year free-from-failure survival was 90.7% and 98.3% (p<0.02) in group 1 and 2 respectively; free-from-metastases survival 96.9% and 97.9% (p<0,08)for group 1 and 2; and cause-specific survival 97.4% and 98.3% (p<0.09). HRQoL was evaluated before treatment, at 3 months interval during the first year follow up and in a yearly basis until 10-year. I-PSS and EORTC’s QLQ-C30 with PR-25 were used. I-PSS scores at 1, 3 and 6 months and at 1, 2, 3, 5 and 8 years follow-up were 6.39, 5.00, 2.52, 2.21, 2.35, 3.65 and 1.43 for group 1 pts and 1.50, 1.10, 1.01, 1.05, 0.89, 0.66, 0.67 for group 2 pts. Global HRQoL scores at 1, 3 and 6 months and at 1, 2, 3 and 5 years follow up were 5.56, 5.75, 5.33, 6.00, 5.40, 5.58 and 5.11 for group 1 pts and 5.60, 6.40, 5.78, 5.89, 5.83, 6.37, 6.00 for group 2 pts, being found to be statistically significant at 3 and 5 years follow up (p<0,001 and p<0,024). Conclusions: High-dose 3D-IMRT + HDR brachytherapy was found to be a method of escalating the dose to the prostate that not only increased the chances of cure for patients if not increased their long-term Health Related Quality of Life.
Clinical significance of plasma fibrinogen level in patients with prostate cancer.
Authors: Ma Xiao-Kun , Wen Jing-Yun , Chen Zhan-Hong , Lin Qu , Li Xing , Dong Min , Wei Li , Chen Jie , Wang Tian tian , Ruan Dan-Yun , Lin Ze-Xiao , Wan XiangBo , Wu Xiang-Yuan
Published: March 2020

e16077

Background: Most of malignant tumor patients have hypercoagulable state with plasma fibrinogen (Fib) levels increased. In this study, we aimed to investigate correlation of plasma Fib with routine prognostic factors of prostate cancer patients, including Gleason score, prostate specific antigen (PSA), TNM 7th Stage. Methods: From January 2007 to December 2012, 107 patients with prostate cancer and 44 cases of benign prostatic hyperplasia (BPH) were included in our study. Automated coagulation analyzer was used to determine the plasma fibrinogen levels. Results: The patients presented a mean age of 70.6 years, a mean PSA level of 28.73 ng/ml, clinically localized prostate cancer in 47 cases, locally advanced condition in 27cases, and distant metastatic disease in 33 cases. The fibrinogen levels were increased in cancer patients compared to that in patients with BPH (P = 0.031). Higher fibrinogen levels related to metastasis, higher TNM stage and increased PSA (p = 0.000, 0.041 and 0.004 respectively). Fib levels were irrelevant to T state, N state, and Gleason score. Conclusions: Prostate cancer patients displayed increased Fib levels. Plasma Fib is significantly increased in patients with higher PSA level,worse TNM stage and distant metastasis. The patients with high Fib might presented relative worse prognosis and should be monitored closely. [Table: see text]
Safety of cabazitaxel in elderly patients with metastatic castrate resistant prostate cancer (mCRPC) previously treated with docetaxel therapy.
Authors: Gernone Angela , Calderoni Giuseppe , Vallarelli Simona , Montagna Elisa , Pagliarulo Arcangelo , Silvestris Francesco
Published: March 2020

e16081

Background: Cabazitaxel (Cab) is a novel taxane for treatment of mCRPC in progression during or after Docetaxel therapy. However, the management of elderly pts also depends on comorbidities that may impact the performance status and influence the treatment decisions. This study was aimed to assess both activity and safety of Cab in a cohort of ≥ 65 yrs aged patients with mCRPC unresponsive to Docetaxel. Methods: Between 11/2011 and 01/2013, 26 pts with mCRPC relapsing after Docetaxel as first line treatment were enrolled following their comprehensive geriatric assessment for eligibility to the study also extended as EAP. The Cab schedule included 25 mg/m2 every three weeks plus 10 mg Prednisone (P) daily. Comorbidities were assessed using the cumulative illness rating geriatric scale (CIRS-G) with 0-4 score. Median age was 73 yrs (65-89), ECOG PS 0-2, median baseline PSA was 107 ng/ml, whereas comorbidities included pneumonia, arterial hypertension, arrhythmias and diabetes. Pts were managed every 3 months by CT, whereas both response rate (RR) and correlations between comorbidities and toxicity were the endpoints of the study. Results: Pts received the CabP schedule with none dose reduction. Minimal adverse effects were recorded as grade 3-4 anemia whereas no episodes of neutropenic fever were observed. Sexteen/26 pts entered in EAP study. Comorbidities were recorded as GIRS-G1-2 in 17 pts, G3 in 7, and G4 in 2. 9/26 pts received total previous docetaxel dose < 1200 mg/tot and 17/26 pts received ≥ 1200 mg/toto. Among the CabP-treated pts, 3 of them showed partial response with one year of median duration and PSA response ≥ 50%, whereas 8 maintained a stable disease with 9 months of median duration and PSA response < 50%. Conversely, 15 pts underwent progression after 5 months of CabP treatment. Conclusions: Our data suggest that comorbidities in mCRPC ≥ 65 yrs aged pts do not interfere with the toxicity of CabP thus supporting its efficacy and safety in older pts unresponsive to previous Docetaxel therapy. Therefore, CabP does not impact the quality of life and emphasizes a proper disease control (PR+SD) in 11/26 pts.
Cabazitaxel in docetaxel-pretreated metastatic castration resistant prostate cancer (mCRPC): Canadian experience.
Authors: Sridhar Srikala S. , Winquist Eric , Hubay Stacey , Assi Hazem , Berry Scott R. , Stewart John , Levesque Eric , Aucoin Nathalie , Czaykowski Piotr , Saad Fred
Published: March 2020

e16082

Background: Cabazitaxel/prednisone (CbzP) improves survival in docetaxel resistant mCRPC. Canadian investigators collected safety, QoL and efficacy data in patients (pts) from a global Expanded Access Program. Methods: Following progression on or after docetaxel, all pts received cabazitaxel 25 mg/m² IV q3wkly and prednisone 10 mg daily. Safety and QoL were collected at baseline and at each cycle. Adverse events were graded according to NCI CTCAE v 4.0. Present pain intensity (PPI) and analgesic scores were assessed using the McGill-Melzack questionnaire. QoL was assessed using FACT-P and EQ 5D-3L. PSA was done at the investigator's discretion at each cycle and at the end of treatment. Results: 61 pts were enrolled at 9 centers. Median age was 65 (18% ≥ 75); 92% were ECOG 0/1; 89% had bone metastases and 21% had visceral metastases. Pts had a median of 9 cycles (median cumulative dose 675 mg/m2) of prior docetaxel, and 38% had progressed on or within 3 months of it. Notably 26 pts (43%) had also received and progressed on prior Abiraterone Acetate (AA) given before (5pts), or after docetaxel (21 pts). Half the patients (51%) received >6 cycles of CbzP. Median relative dose intensity was 99%. At cycle 1, 31% received prophylactic G-CSF. Main grade 3+ toxicities were anemia 9.8%, diarrhea 8.2%, fatigue 8.2% and febrile neutropenia 6.6%. Peripheral neuropathy was uncommon (4.9% ; no grade 3+). There was 1 treatment related death (1.6%) due to abdominal sepsis. Compared to baseline, PPI scores improved despite stable analgesic use and were significant at cycles 2, 4, 9 (p<0.05). The FACT-P prostate specific questions showed significant improvements in the first 4 cycles (p<0.05). On the EQ-5D-3L the percentage of patients reporting “no problem” for the pain domain by the last cycle increased. The PSA response rate (≥50% decrease) was 48.7% in 39 evaluable pts and was similar in AA pretreated and non-pretreated pts (47.1% and 50.0% respectively). Conclusions: In routine clinical practice, CbzP treatment was clinically manageable and toxicities were similar to the TROPIC study. PPI and QoL data support a palliative benefit of CbzP. PSA response rate was 48.7% and similar in AA pretreated and non-pretreated pts.
Effect of ET-1, FGF-2, and HGF on intracellular steroidogenesis in prostate cancer cells.
Authors: Vasileiou Chrysoula , Hatzidaki Eleana , Karkabounas Athanasios , Maragkouli Eleni , Vaiou Maria , Dimas Konstantinos , Liakos Panagiotis , Lekka Marilena , Papandreou Christos
Published: March 2020

e16083

Background: In the prostatic epithelium endothelin-1 (ET-1), fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell proliferation and inhibition of apoptosis. The aim of this study is to investigate whether neuropeptides such as ET-1 and growth factors such as FGF and HGF may constitute an alternate pathway to intracellular steroidogenesis. Methods: PC3 cells, an androgen independent prostate cancer cell line were cultured in RPMI 1640, fully supplemented with FBS 10% and in serum free conditions. The cells were incubated with ET-1(10nM, 3 hrs incubation), FGF-2 (10 ng/ml, 3 hrs incubation) and HGF(33 ng/ml, 3 hrs incubation), and then progesterone, 17-OH progesterone and aldosterone were measured in cell lysates by LC-MS using LTQ Orbitrap XL MS 2.5.5 SP1 (Thermo-Fisher) equipped with Accela AS 2.2.1, Accela pump. The data were analysed by Xcalibur 2.1.0 Software. Results: In baseline conditions PC3 cells produce no progesterone but high amounts of 17-OH progesterone and small amounts of aldosterone. Upon stimulation with endothelin there was a significant increase in progesterone, significant decrease in 17-OH progesterone and a very significant increase in aldosterone. Similarly stimulation with both HGF and FGF resulted in significant decreases in 17-OH progesterone and increases in aldosterone. Conclusions: Our results imply that in androgen deprivation conditions intracellular steroidogenesis can still take place by stimulation via seven membrane and tyrosine kinase receptors, contributing in part to a steroid dependent phenotype in addition to a steroid independent one, thus implying the potential for new therapeutic interventions.
Efficacy and toxicity of q 2 weeks docetaxel versus weekly versus q 3 weeks in metastatic castration-resistant prostate cancer (CRPC).
Authors: Malhotra Akshiv , Rosenbaum Paula , Poiesz Bernard J.
Published: March 2020

e16087

Background: Standard treatment for metastatic CRPC is docetaxel 75 mg/m2q3weeks. Methods: We retrospectively studied patients treated with q 1, 2, or 3 weeks docetaxel regimens at 30, 60 and 75 mg/m2, respectively. The choice of regimen and duration of treatment was decided by their oncologist. Patients who had been in a clinical trial previously, or treated with any other chemotherapy before docetaxel were excluded. On this basis 41 patients were studied. Prostate specific antigen (PSA) was used as the primary method to assess response and progression. Response was a decline of >/=50% from baseline value with no clinical or radiographic evidence of disease progression. For patients whose PSA did not decrease, progression was a >/= 25% increase from baseline. If the PSA decreased without reaching response criteria, progression was a >/= 25% increase from nadir. In those who responded, progression was a >/= 50% increase from nadir. The increase had to be at least 5ng/ml. Toxicity was graded on the basis of CTCAE version 4.0. Response rate and toxicity in the 3 arms was compared using a two by two square t-test. Results: There were 12, 14 and 15 patients in the q1w, q2w and q3w arms, respectively. Response rates, mean progression free survival (PFS), median PFS, mean overall survival (OS), median OS, mean cumulative dose (MCD) and toxicity are shown in table 1. Toxicity was similar in the q1w, q2w and q3w arms, except grade 1/2 neuropathy was higher in the q2w arm vs. the q1w arm (p=0.005). Conclusions: The MCD, response rates, PFS and OS in the q1w and q3w arms were similar to previously published reports. Patients in the q2w arm received a statistically significant higher MCD. Our data suggest a better outcome in the q2w arm as compared to the q1w and q3w arms. However, given the small number of patients studied, the results are not statistically significant. Toxicity was similar save for grade1/2 neuropathy. [Table: see text]
Low-dose metronomic oral cyclophosphamide plus prednisone for castration resistant prostate cancer (CRPC): A retrospective study.
Authors: Martinez Lago Nieves , Anido Herranz Urbano , Leon Mateos Luis , Vieito Maria , Varela Ponte Rafael , Aguin Losada Santiago , Brozos Vazquez Elena , Carmona Campos Marta , Rodriguez Lopez Carmela , Cortegoso mosquera Alexandra Sabela , Candamio Folgar Sonia , López López Rafael
Published: March 2020

e16095

Background: CRPC remains a therapeutic challenge, although in recent years the introduction of new agents has allowed an improvement in overall survival of these patients. In the literature there are few data on the use of cyclophosphamide in this context. The current study was designed to evaluate the efficacy and toxicity of the metronomic oral administration of a combination of cyclophosphamide and prednisone in patients with CRPC, not candidates for docetaxel or after progression to it. Methods: We retrospectively evaluated the medical records of all patients with metastatic CRPC who were treated with prednisone and cyclophosphamide in our institution. Patients had been previously treated with a docetaxel-containing regimen or were not considered candidates for taxanes, because of important comomorbidities or poor Performance Status (PS). Results: Data from 40 patients treated with cyclophosphamide 50 mg/day vo and prednisone 5 mg bid from January 2010 to December 2012 has been analyzed. Baseline characteristics of the patients are listed in the Table. 36 patients were evaluable for efficacy and toxicity. The PSA response rate (RR) was 30%, with partial responses in 7/40 patients. The clinical benefit (stabilization disease + RR) was 52%. Median progression-free survival was 13 weeks (95% CI 13.2 – 14.5). Median overall survival was 46 weeks (95% CI 26.4 – 65.9). The overall 1-year and 2-year survival were 32% and 8 %, respectively. The treatment was safe and well tolerated. Anemia (grade 0-3) was observed in a third of all patients. Conclusions: In this study in patients with a poor prognosis, metronomic oral cyclophosphamide plus prednisone have demonstrated efficacy with excelent tolerance. Oral cyclophosphamide is an interesting alternative to consider in patients non candidates for intravenous chemotherapy. [Table: see text]
Incidence of bone fracture in Japanese patients receiving long-term hormone therapy for prostate cancer.
Authors: Uemura Hiroji , Fusayasu Hideo , Ohtake Shinji , Hayashi Narihiko , Yokomizo Yumiko , Miyoshi Yasuhide , Kubota Yoshinobu , Izumi Kouji
Published: March 2020

e16098

Background: For patients with advanced prostate cancer, long-term treatment of androgen deprivation has been conventionally performed. Among the adverse events such as hormonal therapy, bone fracture due to osteoporosis or metastatsis is one of indispensable events. We assessed the frequency of bone fractures in Japanese patients received hormonal therapy. Methods: Between 2000 and 2010, 1,108 Japanese patients were treated with hormonal therapy including GnRH agonist plus anti-androgens or GnRH agonist alone at Yokohama City University Hospital. Of those patients, 48 patients (4.3%) had bone fractures during their treatment. In this retrospective study, we examined the association of bone fracture with the long-term hormonal therapy by investigating the duration of hormonal therapy, fracture sites, and the occurrence of fracture in castration resistant prostate cancer (CRPC) patients. Results: The median age of the patients with fracture was 77 (60-85) years; the median duration from the start of hormonal therapy to fracture was 29.4 (5.4-110.4) months. Eight patients with CRPC had pathological fractures at bone metastases. With respect of fracture sites, 22 patients (46%) had spinal fractures and 10 patients (21%) had fracture of lower legs. Of 8 CRPC patients, 7 patients had spinal fracture after long-term hormonal therapy (median: 38.6 months, range: 15.7-99.1 months). Conclusions: Japanese patients with prostate cancer treated with hormonal therapy have lower risk for bone fracture compared with those in western countries and USA, and interestingly, it is recognized that vertebral body is vulnerable to fracture in Japanese, especially in CRPC patients treated for long-term hormonal therapy. Because bone fracture in patients with prostate cancer endanger their prognosis, the bone management how to prevent bone fracture is very important during hormonal therapy. For the purpose of it, more detailed analysis in this retrospective study should be required.
Outcome analysis of locally advanced adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma of cervix after definitive radiotherapy.
Authors: Chen Jenny Ling-Yu , Huang Chao-Yuan , Kuo Sung Hsin , Cheng Jason C.
Published: March 2020

e16503

Background: To compare tumor characteristics, treatment response, failure patterns, and clinical outcome of patients with cervix locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) and squamous cell carcinoma (SCC). Methods: Medical records for 36 patients with stage IIB–IVA histologically proven cervix AC/ASC and 199 patients with SCC who received definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) between 1995 and 2009 were retrospectively reviewed. The clinicopathologic features, radiation dose, treatment response, recurrent pattern, metastases pattern, and survival outcome between histologic groups were evaluated. Results: Compared with the SCC subgroup of patients, patients with AC/ASC were significantly younger (mean age, 56 vs. 62 years, p=0.007), more of them without clinical symptoms were diagnosed by abnormal Papanicolaou smear findings (16.7% vs. 5.5%, p = 0.019), and less responded to treatment (complete response, 72.2% vs. 86.9%, p = 0.024). After a median follow-up of 59.3 months, patients with AC/ASC had worse 5-year recurrence-free survival (RFS) (33.7% vs. 58.7%, p = 0.046), worse 5-year distant metastasis-free survival (40.2% vs. 70.3%, p = 0.002), and trends toward worse 5-year local recurrence-free survival (62.4% vs. 75.7%, p = 0.127) and worse 5-year overall survival (OS) (40.1% vs. 58.0%, p = 0.062) than those with SCC. In univariate analysis, early FIGO stage and complete treatment response were found to be significantly associated with both RFS and OS. Histology of non-AC/ASC and Point A biologically equivalent doses in 2-Gy fractions >85Gy were significantly associated with better RFS, and CCRT was significantly associated with better OS. In multivariate analysis, complete treatment response remained significant factor for predicting better RFS, and early FIGO stage, CCRT and complete treatment response remained significant factors for predicting better OS. Conclusions: Cervix AC/ASC may behave more aggressively than does SCC. For this subgroup of cervical cancer, more comprehensively effective treatment is warranted.