bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of prior docetaxel (D) on sipuleucel-T (sip-T) product parameters in PROCEED patients (pts).
Authors: Higano Celestia S. , Armstrong Andrew J. , Cooperberg Matthew R. , Kantoff Philip W. , Bailen James , Concepcion Raoul S. , Kassabian Vahan , Dakhil Shaker R. , Finkelstein Steven E. , Vacirca Jeffrey L. , Rifkin Robert M. , Sandler Andrew , McCoy Candice , Whitmore James Boyd , Tyler Robert Claude , Sartor A. Oliver 
Published: March 2020

5034 Background: Sip-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic mCRPC. The IMPACT trial excluded pts who received D ≤3 months prior to registration. PROCEED is an ongoing, phase IV registry, enrolling pts treated with commercial sip-T. Use of D prior to sip-T is not restricted, so prior D affect on sip-T immune manufacturing parameters can be evaluated. Methods: Pts treated with sip-T ≤ 6 mo were eligible to provide informed consent. Sip-T parameters assessed included: total nucleated cell (TNC) count, antigen presenting cell (APC) count (CD54+large cells) and APC activation (upregulation of CD54). Results: By Nov. 2012, 108/761 (14%) received D prior to sip-T and had similar median cumulative APC counts (1.83 [Q1, Q3: 1.16, 2.71] vs. 1.82 [1.27, 2.70] x 109) and TNC counts (10.16 [7.30, 13.69] vs. 11.47 [8.56, 15.31] x 109) vs. D naïve, whereas median cumulative APC activation appeared slightly lower (32.39 [25.05, 41.02] vs. 34.84 [28.71, 42.83]), but was well above the release criterion for each infusion (2.6 fold). The group was then split by Eastern Cooperative Oncology Group Performance Status (ECOG PS) and Gleason scores (Table). Conclusions: Pts with D prior to sip-T appeared to have product parameters comparable to pts without prior D, albeit with a slightly lower APC activation. Further analysis showed that pts receiving D within 3 months of sip-T had higher Gleason and ECOG scores. The clinical significance of these findings is unclear, but suggests that APC activation is not impaired following docetaxel. Clinical trial information: NCT01306890. [Table: see text]
The association between pre-treatment serum 25-hydroxyvitamin D and survival in stage IV prostate cancer.
Authors: Vashi Pankaj G. , Gupta Digant , Trukova Kristen , Lambert Gwendolyn M , Lammersfeld Carolyn 
Published: March 2020

5036 Background: Emerging evidence in the literature suggests a positive association between serum 25-hydroxyvitamin D [25(OH)D], a standard indicator of vitamin D status, and survival in certain types of cancer. We investigated this relationship in newly diagnosed stage IV prostate cancer patients. Methods: A case series of 54 newly diagnosed stage IV prostate cancer patients underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between Jan 2008 and Dec 2010. We defined vitamin D insufficiency as serum 25(OH)D levels of <=32 ng/ml. Patient survival was defined as the time between date of first patient visit and date of death from any cause/date of last contact. Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for age, prostate specific antigen (PSA) and functional status. Results: Mean age at diagnosis was 59.6 years. During a median follow-up of 23.6 months, 16 deaths occurred. The mean serum 25(OH)D was 30.1 ng/ml, among whom 38 (70.4%) were insufficient in vitamin D (<=32 ng/ml). Mean overall survival was 49.4 months (95% CI: 38.1-60.7). Mean survival was 32.6 months and 62.4 months for patients in <=32 ng/ml and >32 ng/ml groups respectively (p = 0.02). On univariate analysis, patients with levels >32 ng/ml had a significantly lower risk of mortality compared to those with levels <=32 ng/ml (HR=0.19; 95% CI: 0.04-0.87; p=0.03). On multivariate analysis controlling for age, performance status and PSA, patients with levels >32 ng/ml demonstrated significantly lower mortality (HR=0.13; 95% CI: 0.02-1.0; p=0.05) compared to those with levels <=32 ng/ml. Conclusions: Higher circulating levels of serum 25(OH)D were positively associated with survival in patients with metastatic prostate cancer. While these results need to be confirmed in prospective clinical trials, our study adds to the growing body of literature on the prognostic role of serum vitamin D in cancer. Given the high prevalence of vitamin D insufficiency in prostate cancer and the fact that this insufficiency is easily correctable by supplementation, we recommend early vitamin D assessment and intervention for a potential impact on patient survival.
Phase II trial of intravenous carboplatin (C), oral everolimus (E), and prednisone (P) in docetaxel-pretreated (DP) metastatic castrate-resistant prostate cancer (mCRPC): A Prostate Cancer Clinical Trials Consortium study.
Authors: Veeraputhiran Muthu Kumaran , Shevrin Daniel H. , Stein Mark N. , Heilbrun Lance K. , Smith Daryn , Li Jing , Dickow Brenda , Heath Elisabeth I. , Vaishampayan Ulka N. 
Published: March 2020

5041 Background: A phase II clinical trial was conducted of the combination of C and E due to the synergy noted. Methods: The primary endpoint was time to progression (TTP). Intravenous C at a target AUC of 5 on day 1, and oral E 5mg once daily and P 5mg twice daily were administered in 21 day cycles. PSA was assessed every 21 days and radiologic response was assessed every 3 cycles. Secondary endpoints included overall survival (OS), the correlation of TTP with phosphorylated (p) mTOR, pAKT, p70S6, and circulating tumor cells (CTC). A 1-stage study design assumed: a reference median TTP = 1.5 months; 1-sided alpha = 0.15; and power = 0.90, requiring 26 patients (pts). Results: 26 pts enrolled; median age 69 years (range 54-86) ;8 African American and 18 Caucasians. Median pretherapy PSA was 190 ng/ml (range 13 - 2174). 18 pts (69%) each had bone pain and Gleason score > 8. 125 cycles have been administered; median 3 cycles (range 1 - 16). Predominant grade 3 or 4 toxicities were thrombocytopenia in 8 pts, pulmonary embolism in 2 and neutropenia in 3. No treatment related deaths occurred. 4 (15%) had a > 30% PSA decline and 1 had a >90% PSA decline. 8/19 pts had stable disease but no objective responses in MD. The median TTP and OS were 2.5 months (90% CI: 1.8 - 4.3), and 12.5 months (90% CI: 6.7 - 16.1), respectively. Median area under curves were 5.9 (range, 4.3 – 11.0) and 4.5 (range, 4.1 – 7.1) mg/mL*min with C given alone and in combination with E, respectively. E did not influence pharmacokinetics of C. Median baseline CTC (n=18) was 30 (range 0-2372). 5/18 pts had favorable CTC (CTC<5/7.5 mL) pretherapy. Patients with TTP >18 weeks had reduction in post-therapy CTC with a median decrease of 63% (range 11%-100%). Lack of IHC staining for pAKT was noted in 2/2 pts on therapy for > 30 weeks vs increased expression was noted in 8/8 pts on therapy for < 9 weeks. Testing for TSC1 mutation is planned and will be reported. Conclusions: The combination was tolerable but revealed modest clinical efficacy. Biomarker evaluations such as pAKT may help identify a subset likely to benefit from mTOR inhibitor strategy in mCRPC. Clinical trial information: NCT01051570.
The impact of technology diffusion on treatment for prostate cancer.
Authors: Schroeck Florian Rudolf , Kaufman Samuel R , Jacobs Bruce L , Miller David Christopher , Hollenbeck Brent K. 
Published: March 2020

5044 Background: Robotic prostatectomy and intensity modulated radiotherapy (IMRT) hold the promise of improving cancer control and minimizing side-effects for patients with prostate cancer, but are associated with significant upfront investments. Many worry that the perceived advantages of these new technologies and the need to recoup start-up costs could shift decision making in favor of local therapy in lieu of expectant management. In this context, we examined the association of market-level technology penetration with receipt of local therapy. Methods: We used the Surveillance Epidemiology and End Results (SEER) - Medicare linked database to identify all patients with loco-regional prostate cancer who were treated or managed expectantly from 2003 to 2007 (n=59,241). We measured technology penetration as the number of providers performing robotic prostatectomy or IMRT per population in a market (hospital referral region). We then performed multinomial logistic regression to examine the association of technology penetration with receipt of prostatectomy, radiotherapy, or no local therapy. Results: For each 1,000 patients diagnosed with prostate cancer, 171 underwent prostatectomy, 493 radiotherapy, and 336 had no local therapy. Markets with high robotic prostatectomy penetration had higher use of prostatectomy (175 vs. 141 per 1,000 men, p=0.004) but decreased use of radiotherapy (584 vs. 613 per 1,000 men, p=0.046), resulting in a stable rate of local therapy (Table). High versus low IMRT penetration did not significantly impact use of prostatectomy and radiotherapy (Table). Conclusions: Increased penetration of robotic surgical technology was associated with more use of prostatectomy and less use of radiotherapy. However, increased penetration of both robotic prostatectomy and IMRT did not change the overall rate of local therapy. Our findings allay concerns that new technology spurs additional local therapy of prostate cancer. [Table: see text]
Phase III, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and vinorelbine in trastuzumab-resistant, advanced breast cancer (BOLERO-3).
Authors: O'Regan Ruth , Ozguroglu Mustafa , Andre Fabrice , Toi Masakazu , Jerusalem Guy Heinrich Maria , Wilks Sharon , Isaacs Claudine , Xu Binghe , Masuda Norikazu , Arena Francis P. , Yardley Denise Aysel , Yap Yoon Sim , Mukhopadhyay Pabak , Douma Shyanne , El-Hashimy Mona , Taran Tanya , Sahmoud Tarek , Lebwohl David Edward , Gianni Luca 
Published: March 2020

505 Background: Everolimus (EVE) is an inhibitor of mammalian target of rapamycin (mTOR), a protein kinase central to a number of signaling pathways regulating cell growth and proliferation. Data from preclinical and phase 1/2 clinical studies indicated that adding EVE to trastuzumab (TRAS) plus chemotherapy may restore sensitivity to and enhance efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy. The international BOLERO-3 phase 3 study is being conducted to evaluate the addition of EVE to TRAS plus vinorelbine. Methods: Adult women with HER2+ advanced breast cancer and who received prior taxane therapy and experienced recurrence or progression on TRAS were randomized 1:1 to receive either EVE or placebo (5 mg/day) in combination with weekly TRAS and vinorelbine (25 mg/m2). The primary endpoint is progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, safety, quality of life, and pharmacokinetics. Final analysis will be conducted after approximately 417 PFS events. Results: The trial accrued 569 patients between October 2009 and May 2012. Previous therapy included TRAS (100%), a taxane (100%), and lapatinib (28%). The median age was 54 years, and 76% of patients had visceral metastases, 5% had stable brain metastases, 56% had hormone-receptor–positive disease, 33% had Eastern Cooperative Oncology Group performance status of 1 or 2, and 41% had 3 or more metastatic sites. The median number of prior chemotherapy lines in the metastatic setting was 1. As of February 4, 2013, a total of 396 PFS events were reported. Conclusions: Final PFS analysis will be performed in early May 2013; primary and secondary efficacy endpoints will be presented. Clinical trial information: NCT01007942.
Clinical outcome (CO) evaluation of very old (≥ 80 years) castration resistant prostate cancer (CRPC) patients (pts) treated with docetaxel (DOC): Preliminary results of an Italian multicenter retrospective study (DELPHI study).
Authors: Maines Francesca , Burgio Salvatore Luca , Di Lorenzo Giuseppe , Scognamiglio Florinda , Zustovich Fable , Facchini Gaetano , Gamucci Teresa , Procopio Giuseppe , Bortolus Roberto , Lo Re Giovanni , La Russa Francesca , Bonetti Andrea , Messina Caterina , Lodde Michele , Perin Alessandra , Iacovelli Roberto , Pappagallo Giovanni L. , Veccia Antonello , Caffo Orazio , Galligioni Enzo 
Published: March 2020

5050 Background: Since prostate cancer is mainly diagnosed in pts over 65 yrs of age, castration resistance is usually observed in older pts. In the case of very old pts (≥ 80 years), fear of high toxicity degree limit chemotherapy use due to both pts frailty and several comorbidities occurrence. Moreover, if treated these pts usually receive an adapted chemotherapy, often with a weekly schedule, which in TAX327 trial failed to show survival advantage compared to mitoxantrone. The present retrospective study is aimed to assess CO in this very elderly CRPC population. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all ≥ 80 yrs CRPC pts from participating institutions, treated with DOC in clinical practice, recording the pre and post-DOC clinical history, the DOC treatment details and outcomes. Results: To date we collected a consecutive series of 81 pts from 17 Italian hospitals. The median age was 82 yrs (range 80-90). The median baseline PSA was 107 ng/ml (range 3-1597); 81% of the pts had bone metastases, while nodal, lung and liver metastases were observed in 37%, 6%, and 6% of the pts, respectively. Median Cumulative Illness Rating Scale score was 3 (range 0-11), median Activity Daily Living index score was 0 (range 0-5), median Instrumental Activities of Daily Living score was 0 (range 0-5). The DOC was administered on 3-week or weekly schedule basis (41%/59%). A PSA reduction > 50% and an objective response were observed in 74% and 11% of the pts, respectively. Grade 3-4 toxicities were: neutropenia (11%) , fatigue (8%), diarrhea (1%), renal (2%), and febrile neutropenia (1%). The median PFS and OS were 7 mos and 22 mos, while the 1-year PFS and OS rates were 17.3% and 43.9%, respectively. Conclusions: This data suggests that DOC treatment, both on 3-week or weekly schedule, is able to produce good survival outcomes, comparable to pivotal trials (18 mos), also in highly selected very older (≥ 80 yrs) CRPC pts.
Hematologic safety of Ra-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases from the phase III ALSYMPCA trial.
Authors: Parker Chris , Garcia-Vargas Jose E. , O'Bryan-Tear C. Gillies , Fang Fang , Vogelzang Nicholas J. 
Published: March 2020

5060 Background: In the updated analysis of the ALSYMPCA study, Ra-223 significantly improved median survival by 3.6 mo vs placebo (Pbo) in 921 CRPC patients (pts) with bone mets (HR = 0.695; 95% CI, 0.581-0.832; p = 0.00007) and had a highly favorable safety profile (Parker et al. ASCO 2012). The hematologic safety profile and results from a post hoc analysis assessing prognostic factors for changes in hematologic parameters in ALSYMPCA pts are presented. Methods: Pts were randomized 2:1 to 6 injections (inj) of Ra-223 (50 kBq/kg IV) q4wk or matching Pbo and stratified by prior docetaxel (D) use, total alkaline phosphatase (tALP), and current bisphosphonate use.Multivariate regression analysis was performed to explore the relationship of 6 baseline factors (Table) with maximum % change of hematologic parameters from baseline up to 24 wk on treatment (tx). Results: The updated analysis included 901 pts (safety population; Ra-223, n = 600; Pbo, n = 301). Overall grade 3/4 AEs were similar between Ra-223 and Pbo groups, with neutropenia in 2% and 1%, thrombocytopenia in 6% and 2%, and anemia in 13% and 13% of Ra-223 and Pbo groups, respectively. Tx with Ra-223, prior D use, extent of disease (EOD) > 6 bone mets, and tALP ≥ 220 U/L, but not current bisphosphonate use, were associated with decreases from baseline in hemoglobin (Hb), neutrophils, or platelets; prior EBRT to bone for pain was associated with an increase. The significance of the relationship between baseline factors and changes in hematologic parameters is summarized in the Table. Conclusions: Overall, there was a low risk for hematologic AEs with Ra-223 tx in CRPC pts with bone mets. The strongest prognostic factors for decreases in neutrophils and platelets were Ra-223 tx and prior D use. Baseline tALP ≥ 220 U/L was a strong predictor of decrease in Hb. Clinical trial information: NCT00699751. [Table: see text]
Prognostic factors of survival in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel: Sequencing might matter.
Authors: Angelergues Antoine , Maillet Denis , Flechon Aude , Ozguroglu Mustafa , Mercier Florence , Guillot Aline , Le Moulec Sylvestre , Gravis Gwenaelle , Beuzeboc Philippe , Massard Christophe , De La Motte Rouge Thibault , Elaidi Reza-Thierry , Oudard Stephane 
Published: March 2020

5063 Background: Recently, several new drugs have demonstrated an overall survival (OS) benefit in patients (pts) with mCRPC. Their use must be optimized to maximize patient outcomes. We evaluated prognostic factors of OS in mCRPC pts treated with cabazitaxel (C), a new taxane developed to overcome docetaxel (D) resistance. Methods: Records of 125 consecutive mCRPC pts (median 67 yrs) treated with C (after D) were retrospectively collected in 9 centers (France, n=8; Turkey, n=1). Baseline characteristics, disease history, PSA response, OS and radiological and/or clinical progression-free survival (PFS) were collected. The influence of selected variables on OS was analyzed by multivariate logistic regression. Results: At C initiation, 83.3% of pts were ECOG 0-1, 50.8% had an initial Gleason score of 8-10, 62.9% had pain and 84.8% had radiological or clinical progression. Median duration of response to first-line androgen deprivation therapy was 20 months (mo) and 22% received ≥2 prior D lines. New hormonal agents (abiraterone or enzalutamide) were given before C in 33% of pts and after C in 16%. Median number of C cycles received was 6 (range 2-14). A PSA decrease of ≥50% and ≥30% was reached in 41.3% and 48.8% of patients treated with C. Median OS from first C cycle was 13.3 mo and median clinical and/or radiological PFS was 6.5 mo. In multivariate analysis, OS was significantly reduced in pts with ECOG 2 (HR: 6.05), alkaline phosphatase ≥1.5 ULN (HR: 2.64), lymph node involvement (HR: 1.89). Conversely, OS was significantly prolonged in pts with ≥2 prior D lines (HR: 0.35), prior curative therapy (HR: 0.55), a PSA decrease ≥30% with C (HR: 0.21) and in pts treated with abiraterone/enzalutamide after C (HR: 0.37). Median OS from the first D dose was 65 mo in pts treated with abiraterone or enzalutamide after C versus 39 mo in pts receiving these agents before C. Conclusions: Patients with ≥ 2 prior D lines, PSA response ≥30% with C and treated with new hormonal agents after C experienced a prolonged OS. Conversely, intake of new hormonal agents before C rather than after was associated with a reduced OS from the first D dose. Prospective randomized trials are needed to confirm these results.
Results from a phase I study of enzalutamide in combination with docetaxel in men with prostate cancer.
Authors: Fleming Mark T. , Rathkopf Dana E. , Gibbons Jackie , Peterson Amy C. , Hannah Alison , Forer David , Scher Howard I. , Morris Michael J. 
Published: March 2020

5066 Background: Enzalutamide (ENZA) is a novel androgen receptor (AR) inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (DOC). DOC also prolongs survival in mCRPC and also appears to have anti-tumor effects mediated through the androgen-receptor axis, providing a compelling rationale for combining the two agents. CYP3A4 plays a role in DOC clearance and is induced by ENZA. We therefore conducted a phase I study to explore the PK and safety profiles of this combination. Methods: This study (NCT01565928) evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: Twenty-two pts were enrolled, 4 did not receive 2 full doses of DOC. As of 21 Sept 2012, preliminary PK and C1 and C2 safety data were available from 15 pts. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC<1000/mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone.Final PK and updated tolerability and efficacy data beyond Cycle 2 will be presented. Conclusions: In mCRPC pts, ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.
Association of bone scan index (BSI) with prognostic biomarkers and survival in men with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a prospective randomized controlled trial of tasquinimod.
Authors: Armstrong Andrew J. , Kaboteh Reza , Carducci Michael Anthony , Damber Jan-Erik , Stadler Walter Michael , Mats Hansen , Edenbrandt Lars , Forsberg Goran , Nordle Orjan , Pili Roberto , Morris Michael J. 
Published: March 2020

5081 Background: Tasquinimod (T) is an oral immunomodulatory and anti-angiogenic agent currently in phase 3 testing in mCRPC. In a randomized, double-blind phase 2 multicenter study, 201 men with mCRPC who received T had improved radiographic PFS vs. placebo (P), with a more pronounced effect seen in men with bone metastases. Given the subjectivity/variability of bone scan measurements, we sought to evaluate the bone scan index (BSI), a quantitative and objective measure of BS activity, over time in this controlled clinical trial. Post-treatment BSI changes were examined given their prior association with survival. Methods: In this retrospective analysis, Exini bone™, an automated software package that generates the BSI (percent tumor involvement) from 99Tc BS, was used to calculate BSI over time from BS collected during central review in this randomized trial of T vs. P. Associations between baseline and on-treatment BSI, survival, prognostic biomarkers, and treatment effect were evaluated. Results: 108 men contributed baseline scans for BSI analysis that met quality control metrics (74 T vs. 34 P), 85 of whom (57 T vs. 28 P) had at least 1 evaluable follow-up week 12 scan. Median baseline BSI was 0.90% and after 3 months median BSI was 1.21%. In univariate analysis (n=85) baseline BSI correlated with OS (HR 1.41; p=0.01). Both baseline BSI (HR 1.62; p=0.006) and week 12 BSI change (HR 1.95; p=0.002) remained associated with OS after adjustment for bone alkaline phosphatase, PSA, pain score, hemoglobin, and treatment arm. BSI correlated with baseline PSA, LDH, bone alkaline phosphatase, and the number of bone lesions. The increase in BSI at week 12 vs. baseline was slower with T vs. placebo (0.16% vs. 0.26% increase). Conclusions: BSI and BSI changes were associated with OS in men with mCRPC in this prospective trial. BSI correlates with known biomarkers of OS, but adds independent prognostic information. While underpowered, a delay in objective radiographic bone scan progression with tasquinimod is suggested and the evaluation of BSI and BSI changes in the context of phase 3 trials of men with mCRPC is warranted. Clinical trial information: NCT00560482.