bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic syndrome, diabetes mellitus, and the subsequent development of prostate cancer
Authors: Lawrence Y. R. , Morag O. , Boyko V. , Benderly M. , Goldbourt U. , Barchana M. , Behar S. , Wolf I. , Dicker A. P. , Catane R. 
Published: August 2020

5158 Background: The lifetime risk of an American man developing prostate cancer (PC) is one in six. Metabolic syndrome (MS) is a cluster of medical disorders (hypertension, dyslipidaemia, hyperglycaemia, obesity) associated with the subsequent development of diabetes mellitus (DM). DM and MS afflict 11% and 22% of US adults respectively. MS and DM are associated with disturbed lipid homeostasis, and hypogonadism. DM and MS predispose to the development of gastrointestinal and endometrial cancer. DM and MS's influence on PC is less clear; some studies have suggested that whereas DM inhibits PC, MS promotes PC development. Methods: The Bezafibrate Infarction Prevention study was a randomized trial of fibrate therapy for the secondary prevention of ischemic heart disease. Between 1990–2 15524 men and women with ischemic heart disease were screened, of whom 3090 entered the trial. 81% were male. Participants were divided into three groups according to baseline parameters: (A) those with neither MS nor DM, (B) those with MS but no DM, (C) those with DM (with or without MS). MS was defined according to ATPIII guidelines. DM was defined by medical history or fasting glucose > 125 mg/dL. Follow-up for PC incidence and all-cause mortality was obtained through the Israeli cancer registry and the Ministry of the Interior respectively. Analysis accounts for differences in age and non-cancer-related-mortality between groups. Ethics approval was obtained. Results: 1350 participants were excluded due to missing data or previous cancer diagnosis, leaving 11,541 men. Mean age at enrollment 61 years (45–74). Median follow-up was 12 years. There were 6119 (53%), 3,376 (29%), and 2,046 (18%) participants in groups A, B and C respectively. Overall there were 459 cases of PC; 298, 123 and 48 in groups A, B and C. The age adjusted PC rates were 4.30, 3.61 and 2.55 per 1,000 patient years in groups A, B and C respectively (A vs C p = 0.003). Data were also analyzed examining PC incidence as a function of ‘number of components of MS present’ after pooling groups A, B and C. Relative risk of developing PC was 1.00, 0.92, 0.90, 0.69, 0.71, and 0.33 for 0, 1, 2, 3, 4, and 5 components respectively. Conclusions: A baseline diagnosis of DM (highly significant) or MS (trend) was associated with a decreased prostate cancer rate over the subsequent 12 years. No significant financial relationships to disclose.
Phase III trial comparing 4-cycle doxorubicin plus cyclophosphamide followed by 4-cycle taxan with 8-cycle taxan as adjuvant therapy for node-positive breast cancer: Results of N-SAS-BC02 trial
Authors: Watanabe T. , Kuranami M. , Inoue K. , Masuda N. , Aogi K. , Iwata H. , Mukai H. , Tanaka S. , Yamaguchi T. , Ohashi Y. 
Published: August 2020

516 Background: Anthracyclines are the key agents in postoperative regimens for breast cancer (BC). However, relatively rare but life threatening toxicity such as cardiac failure and secondary leukemia are the major concern with anthracycline containing regimens. Retrospective analyses suggested that anthracyclines can be excluded in some pts. Methods: Eligibility included node positive BC age less than 70 yo. Pts were randomized to receive either AC (doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2) every(q) 3 weeks(wks) x 4 -> P (paclitaxel) 175 mg/m2 q3 wks x 4 (ACP), the same AC -> D(docetaxel) 75 mg/m2 q3 wks x 4 (ACD), P 175 mg/m2 q3 wks x 8 (PTX) or D 75 mg/m2 q3 wks x 8(DTX). Comparison included P vs.D (ACP+PTX vs. ACD+DTX) and with AC or without AC (ACP+ACD vs. PTX+DTX). The primary endpoint was disease free survival (DFS) and the secondary endpoints included overall survival, adverse events (AE) and quality of life (QOL). The trial was powered to prove the non-inferiority of regimens without AC to those with AC (threshold hazard ratio [HR] 1.321) in terms of DFS. Results: 1,060 pts were accrued between Dec. 2000 and Mar.2006. 270 DFS events and 106 deaths after a median follow-up of 46.5 months were observed. In all randomised patients, 8 cycles taxane is not inferior to 4 cycles AC -> 4 cycles taxane in terms of DFS (HR:1.26, 95% CI; 0.99–1.60, p = 0.67). In the subset of HER-2 positive patients, 4 cycles AC -> 4 cycles taxane produced superior DFS to 8 cycles taxane (HR:1.63, 95% CI:1.05 - 2.54) but this is not observed in patients with HER-2 negative patients (HR:1.13, 95% CI: 0.85 - 1.50). D 75 mg/m2 tends to show superior DFS to P 175 mg/m2 (HR: 0.81, 95% CI; 0.64–1.03, p = 0.08). Nausea and vomiting was more frequent with AC -> a taxane than 8 cycles taxane. Edema and febrile neutropenia was more frequently observed with D 75 mg/m2 than P 175 mg/m2. The incidence of sensory neuropathy was higher with P 175 mg/m2 than D 75 mg/m2. Conclusions: AC improved DFS in the subset of pts with HER-2 overexpressing BC but not in non-selected population. DFS was better in the arms containing D than in the arms with P. Higher incidence of severe AEs was observed in the arms containing D than in arms with P. No significant financial relationships to disclose.
MER-101–03, a multicenter, phase II study to compare MER-101 20mg tablets to intravenous zoledronic acid 4mg in prostate cancer patients
Authors: McHugh C. , Madigan K. , Walsh A. , Fox J. , Leonard T. W. , Quint J. B. 
Published: August 2020

5161 Background: The primary objective of this study is to examine the pharmacodynamic effects of two different regimens of zoledronic acid, Orazol 20 mg tablets versus Zometa 4mg IV infusion once-monthly therapy on biomarkers in male bisphosphonate-naïve hormone-refractory prostate cancer patients. Methods: The study is an open-label, multi-center phase II clinical trial to compare oral Orazol 20 mg tablets weekly, to infusions of intravenous Zometa 4mg monthly, in males with hormone-refractory prostate cancer, bone metastases, and no prior bisphosphonate treatment. Patients were assigned into one of three cohorts. The three treatments administered were IV Zometa, 4 mg, 15 minute infusion, Day 0 and Day 28; Orazol po, 20 mg, Days 0, 7, 14, 21, 28, 35, 42, and 49; and Orazol po, 20 mg, Days 0, 1, 2, 3, 28, 35, 42, and 49. The study population consisted of men with hormone refractory prostate cancer as evidenced by history of rising PSA levels (last 2 of 3 PSA levels must be above nadir), who are bisphosphonate-naive, and have radiographically-confirmed bone metastases. Efficacy assessments: The primary endpoints are the assessment of response of four biomarkers, urinary NTX, serum CTX, serum bone specific alkaline phosphatase, and serum calcium on days -7, 0, 7, 14, 21, 28, 35, 42, 49, and 56. Secondary endpoints are assessments of performance and pain scores based on ECOG performance status, BPI, and analgesic use. Safety assessments include physical examinations, vital signs and body weight, hematology panel, urinalysis, and blood chemistry panel. Results: The results demonstrated a rapid decrease for all four biomarkers. This decrease was seen at seven days, and was sustained throughout the study. There were no statistically significant differences between any of the treatments in the primary and secondary endpoints. Conclusions: From the results of MER-101–03, Orazol weekly therapy appears to be as effective as Zometa, based on the biomarkers analyzed. Orazol offers a substantial improvement in therapy over IV infusion for patients, with efficacy that is at least comparable based on the results obtained here. No significant financial relationships to disclose.
Expression of LHRH receptors in prostate cancer cells prior to therapy, following castration, or following treatment with LHRH agonists
Authors: Liu S. , Schally A. V. , Xiong S. , Cote R. , Hawes D. , Fazli L. , Gleave M. , Cai J. , Brands F. , Engel J. , Pinski J. 
Published: August 2020

5163 Background: In the treatment of advanced prostate cancer, the effects of luteinizing hormone releasing hormone (LHRH) agonists are mediated through the down-regulation of pituitary LHRH receptors, inhibiting the pituitary-gonadal axis. Several groups have demonstrated LHRH receptor expression on prostate cancer cells. These tumoral receptors have been shown to mediate direct inhibitory effects in vitro. That expression of LHRH receptors persists in the castrate resistant state. To date, there is no information on LHRH receptor expression on the prostate after LHRH agonist therapy. This study investigates the expression of LHRH receptors following prolonged exposure to LHRH agonists. Methods: Expression of LHRH receptors was determined using immunohistochemistry and the intensity was graded on a scale from zero to 3. The expression was analyzed in three cohorts of patients: (1) 47 men with localized prostate cancer treated with radical prostatectomy with no hormone therapy, (2) 61 men with localized prostate cancer treated with neoadjuvant LHRH agonists for varying duration prior to prostatectomy, and (3) 22 men with metastatic prostate cancer who received a palliative transurethral resection of the prostate after clinical progression. In the final cohort, 15 men were treated with castration and 7 were treated with LHRH agonists. Results: 45 of 47 hormone naïve samples (95.7%) demonstrated LHRH receptor expression. Statistical analysis revealed a correlation between strong receptor expression and higher pathologic tumor stage as well as shorter overall survival. 60 of 61 samples treated with neoadjuvant LHRH agonist therapy (98.4%) demonstrated LHRH receptor expression. All 22 samples from patients with metastatic disease demonstrated LHRH receptor expression. The majority of these samples demonstrated moderate to strong intensity. Conclusions: LHRH receptors are expressed on prostate cancers cells of hormone naïve and castrated patients. The expression of these receptors appears to persist despite prolonged treatment with LHRH agonists. The continued expression of these receptors supports the concept of targeting prostatic LHRH receptors to deliver cytotoxic therapy based on LHRH analogs, such as AN-152. [Table: see text]
Sunitinib in combination with docetaxel and prednisone in patients (pts) with metastatic hormone-refractory prostate cancer (mHRPC)
Authors: Zurita A. J. , Liu G. , Hutson T. , Kozloff M. , Shore N. , Wilding G. , Logothetis C. J. , Chen I. , Chow Maneval E. , George D. 
Published: August 2020

5166 Background: Overexpression of VEGF and PDGF has been implicated in prostate cancer progression and bone metastases. Sunitinib is an oral, multitargeted inhibitor of VEGFRs, PDGFRs, and other tyrosine kinases which may improve the efficacy of chemotherapy in pts with mHRPC. We performed a multicenter phase I/II study of sunitinib in combination with docetaxel and prednisone as first-line therapy in pts with mHRPC. The combination dose was established in phase I (Zurita et al, ECCO. 2007). Final results from phase II will be reported. Methods: Pts received treatment in a 21-day cycle: sunitinib 37.5 mg/d on days 1–14, docetaxel 75 mg/m2 on day 1, and prednisone 5 mg BID on days 1–21. Dose reductions were permitted for treatment-related toxicity. The primary endpoint was PSA response rate (PSA Working Group Criteria). Secondary endpoints included tumor response rate (RECIST), safety and patient-reported outcomes. Results: Fifty-five pts were enrolled and 13 remained on study at the time of the data cutoff (1 Oct 08). Thirty-six discontinued from the study due to disease progression (16), adverse events (AEs; 13), consent withdrawal (6) and other (1). Six pts completed the study (16 cycles) and continued treatment on another protocol. Pts received a median of 23 weeks of therapy (range, 2–84). The most common treatment-related grade 3–4 AEs were neutropenia (75%), febrile neutropenia (15%), fatigue (15%), stomatitis (7%), and anorexia (7%). Sunitinib dose reduction to 25 mg/d was required in 14 pts (26%), and 3 pts (6%) had a further dose reduction to 12.5 mg/d. Docetaxel dose reduction to 60 mg/m2 was required in 18 pts (33%). PSA responses occurred in 31 pts (56%), with a preliminary median time to PSA progression of 42.1 weeks. Out of 33 pts with measurable disease, thirteen (39%) had a confirmed partial response (PR) and another 7 (21%) had an initial PR. The median progression-free and overall survivals have not been reached, but the probability of survival at 48 weeks is 92.4% (95% CI: 77.5, 97.6). Patient-reported assessments of pain and quality of life will be reported. Conclusions: Sunitinib in combination with docetaxel and prednisone is tolerated and has antitumor activity in pts with mHRPC, as indicated by both PSA and RECIST-defined tumor responses. [Table: see text]
Ineligibility of prostate cancer patients in the VA Connecticut Healthcare System (VACHS) to participate in clinical trials due to comorbidities
Authors: Mayer T. M. , Kelly W. K. , Concato J. , Chao H. 
Published: August 2020

5169 Background: A large proportion of prostate cancer patients receive their care within the VA Healthcare System. As this is a population affected by complex comorbidities, they may be underrepresented in oncology clinical trials. Our objective was to quantify the frequency with which castrate resistant prostate cancer (CRPC) patients in VACHS would be excluded from major phase III randomized controlled trials. Methods: We reviewed records of all prostate cancer patients at the VACHS between 2004–2007 and identified patients with CRPC. We reviewed eligibility criteria of 24 major phase III clinical trials, from 2006 onwards, studying investigational drugs for CRPC and created a “master list” (ML) of the most pertinent criteria. We analyzed our patient population according to both the ML criteria and to the TAX327 study criteria. Results: We identified 106 patients with CRPC, excluded 7 patients with insufficient medical records, and analyzed 99 patients. Performance status and life expectancy could not be accurately assessed from most charts and were excluded as specific criteria (though reflected in other serious medical condition). Major reasons for exclusion according to ML/TAX327 criteria include: 10/10 other malignancy within 5 years; 11/14 abnormal laboratory parameters; 27/30 other serious medical conditions; 3/4 abnormal cardiac function. ML list only exclusions: 5 active angina; 1 unstable DM; 1 major GI surgery; 1 contraindication to steroids. Serious medical conditions included: active cardiac disease, dementia, serious neurologic, psychiatric, vascular, pulmonary or hematologic disease, and poor performance status or compliance. Overall, 45% (45/99) of patients were excluded when using both the ML and TAX327 criteria. Conclusions: Approximately half of CRPC patients in the VACHS between 2004–2007 did not meet eligibility criteria for major therapeutic trials for CRPC. This retrospective review demonstrates that VA patients are underrepresented in randomized clinical trials for CRPC and are a special population due to their complex comorbidities. These findings underscore the importance of designing better clinical trials for CRPC with less barriers for this underrepresented but common patient population. No significant financial relationships to disclose.
Visit and treatment patterns over time among elderly patients (pts) with M1 prostate cancer (PC): An analysis using SEER-Medicare
Authors: Hussain A. , Onukwugha E. , Seal B. , Mullins C. D. 
Published: August 2020

5170 Background: Treatment options for the management of pts diagnosed with M1 PC have evolved over time. It is unknown whether visits to medical oncologists/hematologist oncologists (MOH) and treatment patterns are also changing over time. The objective of this study is to examine changes in visit and treatment patterns over time. Methods: A retrospective analysis of SEER Medicare data included pts diagnosed with M1 PC from 1994–2002 (age > 65 years) and residing in SEER registries that were present for the entire period. The study included pts with a post-diagnosis visit to a urologist; pts who saw a MOH prior to the urologist visit were excluded. Pts were grouped as 1) no MOH visit, 2) MOH visit w/in 3 mos of a urologist visit, 3) MOH visit => 3 mos after a urologist visit. Treatment with hormone therapy or chemotherapy was defined as 1) none received; 2) timely (i.e. within 6 mos of diagnosis); and 3) delayed, i.e. => 6 mos following the diagnosis. Time periods were defined as early (1994–1996), middle (1997–1999) and late (2000–2002). Results: 3,269 pts (mean age 77, 81% white) were available for analysis. Ninety-three percent of pts received treatment. Thirty-eight percent of pts saw a MOH during the study period; over the study period (early; middle; late) 13% (10%; 13%; 17%) of pts had a timely visit to the MOH and 25% (24%; 28%; 25%) had a delayed visit to the MOH. The proportion of patients seeing a MOH increased (34%; 41%; 42%, p < 0.001) and the proportion of treated pts increased (93%; 93%; 95%, p = 0.03) over the early, middle, and late periods. Conclusions: Approximately one-third of patients with M1 disease and a post-diagnosis urologist visit also see a medical oncologist. The vast majority of these patients receive treatment. Over time, a larger proportion of patients are seeing medical oncologists. [Table: see text]
Benefit of adjuvant trastuzumab in breast cancer patients with focal HER2 amplified clones: Data from N9831 Intergroup Adjuvant Trial
Authors: Sukov W. R. , Miller D. V. , Dueck A. C. , Tenner K. S. , Jenkins R. B. , Kaufman P. A. , Davidson N. E. , Dakhil S. R. , Martino S. , Roy V. , Perez E. A. 
Published: August 2020

520 Background: Targeted therapy using trastuzumab (an anti-HER-2 receptor monoclonal antibody) has significantly improved survival in breast carcinoma patients (pts), but determining which pts will respond to this therapy remains a challenge. We previously reported (Miller DV, ASCO 2004 abstract #568) a subset of pts with breast cancers demonstrating focal HER-2 amplified clones (FHAC) amidst otherwise nonamplified tumor cells by fluorescence in-situ hybridization. These accounted for 21% of the HER-2 amplified but immunohistochemistry (IHC) negative cases and 30% of the HER-2 amplified but IHC equivocal cases. The clinical significance of this phenomenon was unclear at that time. We now report the disease-free survival (DFS) data on 91 FHAC pts with a comparison to the diffusely amplified (DA) cases in this trial group. Methods: Breast tumors were evaluated for HER-2 gene amplification using PathVysion™. FHAC cases demonstrated 2–40% of cells with >10 HER-2 signals and HER-2:CEP17 ratio >5.0, regardless of the overall HER-2:CEP17 ratio. Patient and disease characteristics were compared using chi-square tests. Cox regression models compared DFS between pts randomized to arms A (standard chemotherapy) and C (standard chemotherapy with concurrent trastuzumab) within 91 FHAC and 1571 DA cases. Median follow up was 4.0 years. Results: Age, race, menopausal status, surgical procedure, nodal status, histologic type and grade, and tumor size, were not significantly different between pateints with FHAC and DA. Pateints with FHAC had more frequent hormone receptor positivity compared to DA cases (66% vs 50%; p = 0.004). Hazard ratios between pts with FHAC and DA showed that both groups of pts had similar DFS (A: HR = 0.86, p = 0.65; C: HR = 0.72, p = 0.57). Hazard ratios between arms within FHAC and DA groups demonstrated similar benefit from trastuzumab in each group (FHAC: HR = 0.50, p = 0.30; DA: HR = 0.59, p < 0.0001). Results remained consistent when including hormone receptor status in the model. Conclusions: Based on a small number (n = 91) of pts with FHAC, benefit from trastuzumab appears to be similar whether the population of HER-2 amplified cells with breast carcinomas is focal or diffuse. [Table: see text]
Impact of study participation on survival of early-stage breast cancer patients: Results from the BRENDA study, a multicenter clinical cohort on quality of breast cancer care
Authors: Kurzeder C. , König J. , Woeckel A. , Sauer G. , Wischnewsky M. , Blettner M. , Kreienberg R. 
Published: August 2020

521 Background: Over the past two decades significant progress in treatment of early breast cancer has been accomplished through well designed, clinical trials (CTs). It has been hypothesized that trial participation could also be beneficial for the individual breast cancer patient. The BRENDA study group has been analysing quality of care provided by one university based and 16 regional breast cancer centers in south germany. In this study we investigated the impact of study participation on survival in an unselected clinical cohort of early stage breast cancer patients. Methods: The study population includes 5,966 patients who received primary therapy for early breast cancer between 1992 and 2005. Influence on survival by study participation was calculated by Cox proportional hazard analyses. Model adjustments include prognostic factors, type of treatment, age, risk group and time period. Guideline compliant treatment was assessed based on the St Gallen expert consensus recommendations and the German national S3 Guidelines. Results: A total of 738 patients (12%) received adjuvant (n = 552) or neoadjuvant (n = 186) systemic therapy within one out of 42 registered prospective multicenter phase II or III clinical trials. For patients not receiving neoadjuvant systemic therapy trial participation was associated with improved overall and disease free survival (hazard ratio [HR] = 0.75, 95% confidence interval [CI] 0.57–0.99, HR = 0.78, CI 0.63 - 0.97, respectively). The calculated effect was of similar magnitude after additional adjustment for co-existing morbidity of patients. Descriptional analysis revealed that guideline violations for locoregional or systemic treatment were more frequently found in patients receiving adjuvant treatment outside CTs. No significant effect on survival was calculated for 183 patients receiving neoadjuvant systemic therapy within CT protocols. Conclusions: In our study population participation in prospective clinical trials for adjuvant systemic therapy was associated with improved survival irrespective of treatment actually given. Intrinsic mechanisms within the framework of clinical trials can improve quality of breast cancer patient care. No significant financial relationships to disclose.