bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost effectiveness of sorafenib versus best supportive care in advanced renal cell carcinoma in Canada
Authors: Jaszewski B. , Gao X. , Reddy P. , Bhardwaj T. , Bjarnason G. , Finelli A. , Kapoor A. , Abugaber A. 
Published: March 2020

5111 Background: Sorafenib is an oral multi-kinase inhibitor that targets tumour cell proliferation and tumour angiogenesis. In the TARGETs study (phase III trial), sorafenib plus best supportive care (BSC) significantly prolonged progression-free survival (PFS) compared with BSC alone (P<0.000001) in patients with advanced renal cell carcinoma (RCC). The objective of this study was to evaluate the costeffectiveness of sorafenib plus BSC versus BSC alone in advanced RCC from a Canadian provincial Ministry of Health perspective. Methods: A Markov model was developed to project the lifetime survival and costs associated with the two treatment groups. The model tracked patients with advanced RCC through three disease states - PFS, progression, and death. Resource utilization included drug, drug administration, physician visits, monitoring, and adverse events. Costs and survival benefits were discounted annually at 5%. Results: The lifetime per patient costs were $62,426 CDN and $18,898 CDN for sorafenib + BSC and BSC alone, respectively. The life-years gained (LYG) were higher for sorafenib relative to BSC. The incremental cost-effectiveness ratio (ICER) of sorafenib plus BSC versus BSC alone over a lifetime horizon was $36,046/LYG CDN (with a half cycle correction). Univariate sensitivity analyses yielded ICERs below $70,000/LYG CDN. Probabilistic sensitivity analyses showed that the results were moderately sensitive to the clinical variables and less sensitive to the cost variables, yielding ICERs below $100,000/LYG CDN in most cases. Conclusion: Sorafenib is cost effective with an ICER of $36,046/LYG CDN which is below the suggested cost effectiveness threshold of $100,000/QALY ($CDN 1992) or $130,860/QALY ($CDN 2006). [Table: see text]
Prospective evaluation of carbonic anhydrase IX (CAIX) as a molecular marker in metastatic renal cell carcinoma
Authors: Klatte T. , Zomorodian N. , Kabbinavar F. F. , Belldegrun A. S. , Pantuck A. J. 
Published: March 2020

5112 Background: CAIX is an important molecular marker of survival and response to immunotherapy in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to prospectively evaluate the performance of CAIX in patients with metastatic RCC. Methods: This study accrued 32 consecutive patients who were treated for metastatic clear cell RCC between January 2004 and May 2006. Immunohistochemical staining of the primary tumor was performed using the mouse monoclonal antibody MN-75. Patients were stratified into two groups: high CAIX expression (>85%) and low CAIX expression (=85%) according to the percentage of cells staining positive for CAIX. Study endpoints included disease-specific survival time (DSS) and response to treatment according to RECIST criteria. Results: Four (12.5%), 21 (65.6%), and 7 patients (21.9%) were classified into low risk, intermediate risk, and high risk groups according to the University of California Integrated Staging System (UISS). Twenty (62.5%) of the 32 patients had high CAIX expression. The median follow-up was 11.4 months. Patients with low CAIX expression had significantly worse prognosis than patients with high CAIX expression (median survival: 15.2 months vs. not reached, p=0.01, 1-year DSS rate: 63% vs. 83%) and a 3.9 fold increased risk of death from RCC (95% CI, 1.2–12.7). All 4 patients in the low risk UISS group had high CAIX expression, and all were alive at 1 year. Nine patients received high dose IL-2 based immunotherapy, including 8 who had high CAIX expression, and a 1-year DSS rate of 87.5%. Of the patients expressing high CAIX, 3 (37.5%) were responders to IL-2 including 1 partial and 2 complete responses, 3 (37.5%) exhibited stable disease and 2 (25.0%) progressed during treatment. Conclusions: The results of this first prospective study of CAIX in metastatic RCC confirm that high CAIX expression is associated with better survival and enhanced response to IL-2 based immunotherapy. Patients with high CAIX expression, specifically those with low risk RCC, should be considered candidates to receive immunotherapy, whereas patients with low CAIX expression or in higher risk groups may be better candidates for targeted or other experimental therapy. No significant financial relationships to disclose.
Osteopenia (OP) induced by 6 and 18 months androgen deprivation (AD)
Authors: Ball J. 
Published: March 2020

5123 Background: In a trial evaluating the optimal duration of AD in locally advanced prostate cancer (PC) we sought to determine whether 18 months of zoledronate (Zd) would reverse AD induced OP and reduce bony failure. Methods: In the four arm 2x2 TROG 03.04 (RADAR) trial, men with T2b,c-4 and T2a (Gleason score >6, PSA >10) N0 M0 PC (but without osteoporosis) were randomised to leuprotide (Lp) 22.5 mgs i.m. 3 monthly for 6 months starting 5 months prior to radiotherapy (RT) in Arm A, or the same treatment with Zd mgs i.v.i. 3 months for 18 months commencing on Day 1 (in Arms B and D), or with Lp 22.5 mg i.m. 3 monthly for 12 months after RT (in Arms C and D). Hip and spinal bone mineral densities (BMD) were measured before treatment (bt) and then at 2 and 4 years using DEXA and differences between trial arms were assessed by paired t tests. OP was defined by T- scores <-1. Results: Between October 2003 and January 2006, 930 men were randomized. 124 men with BMD measures bt and at 2 years are evaluable. Mean change (±SD) in BMD between 0 and 2 years was -0.005 ±0.05 (p=0.57) in Arm A, 0.085 ±0.06 (p=<0.001) in Arm B, 0.054 ±0.07 (p=<0.001) in Arm C, and 0.065 ±0.05 (p=<0.001) in Arm D. 98 men had normal BMD bt. Of these 6 of 51 in Arms A, C (no Zd) have developed OP at 2 years while none of 47 in Arms B, D (+Zd) have as yet. Conclusions: At 2 years OP caused by 6 months AD is minimal, but remains significant after 18 months AD. This is reversed by 18 months Zd, but further follow up will determine whether this degree of OP resolves with time or causes fractures. No significant financial relationships to disclose.
Effect of toremifene in lowering total cholesterol, LDL, and triglycerides and raising HDL in prostate cancer patients on androgen deprivation therapy
Authors: Smith M. , Chu F. , Forrest J. , Malkowicz S. B. , Price D. , Sieber P. , Barnette K. G. , Rodriguez D. , Steiner M. S. 
Published: March 2020

5124 Introduction: Androgen deprivation therapy (ADT) is the standard treatment for men with advanced prostate cancer. ADT has been shown to detrimentally affect lipids (average 9% increase in total cholesterol and 26% increase in triglycerides) and is associated with increased risk of coronary heart disease and myocardial infarction. Toremifene, a selective estrogen receptor modulator (SERM), improves bone mineral density and lipid profiles in women. An ongoing phase III trial will assess the safety and efficacy of toremifene in treating multiple side effects of ADT including osteoporosis, hot flashes, gynecomastia and lipid profiles. Given the emerging recognition of increased cardiovascular risk during ADT, an interim analysis was conducted to assess the effects of toremifene on lipid profiles in the ongoing phase III study. Methods: 1,392 men = 50 years old with histologically documented prostate cancer and receiving ADT were randomized to toremifene (80 mg/day) or placebo. An interim analysis evaluated changes in lipids from baseline to month 12 in the first 197 subjects to complete one-year follow up. The outcomes measured in this interim analysis were total cholesterol, LDL cholesterol, triglycerides, total cholesterol/HDL ratio, and HDL cholesterol. Results: Compared to treatment with placebo, toremifene decreased total cholesterol (7.1%; p=0.001 for between group comparison), LDL cholesterol (9.0%; p=0.003), and triglycerides (20.1%; p=0.009) levels, and the total cholesterol/HDL ratio (11.7%; p<0.001). Toremifene also significantly increased HDL levels (5.4%; p=0.018) compared to placebo. The effects of toremifene were observed in both statin users and nonusers. Conclusions: Toremifene decreases total cholesterol, LDL cholesterol, and triglycerides and increases HDL cholesterol in men receiving ADT for advanced prostate cancer compared to placebo. Conclusions regarding the clinical significance of these observations will be based on the full cohort of patients at the conclusion of the trial. No significant financial relationships to disclose.
Cardiac safety in patients (pts) with metastatic breast cancer (MBC) treated with lapatinib (L) and trastuzumab (TRA)
Authors: Storniolo A. M. , Koehler M. , Preston A. , Rappold E. , Byrne J. , Ewer M. S. 
Published: March 2020

514 Background: Clearly defined standards for assessing cardiac toxicity do not exist for newer agents used as treatment for BC, e.g., tyrosine kinase inhibitors. To evaluate the usefulness of increased cardiac monitoring and cardiac function (LVEF) in pts treated with L+TRA, data from 4 trials were analyzed. Methods: From July 2003 to Dec 2006, 238 pts received L+TRA (n=203) or L+TRA with paclitaxel or docetaxel (n=35) for HER2-positive MBC. LVEF was evaluated at screening, every 8 weeks after starting L+TRA, and at withdrawal via multiple-gated acquisition scans or echocardiograms. Rate of symptomatic cardiac events (CE; NCI CTCAE Grade 3 or 4 LV systolic dysfunction) or asymptomatic LVEF decreases (=20% relative to baseline and below the institution’s lower limit of normal) were assessed. Results: None of the 238 pts had a symptomatic CE. Four pts had a single asymptomatic LVEF decrease and 1 pt had 2 asymptomatic LVEF decreases, totaling 6 decreases in 5 (2.1%) pts. These pts were women aged 36–64 years and had previously received anthracyclines (A; n=2), A+TRA (n=2), or unknown therapy (n=1). Median time to onset of LVEF decrease was 83 days; all but 1 decrease occurred within 75 days after initiating L+TRA (range: 18–221 days). Baseline LVEFs of 62%, 60%, 62%, 74% and 58% decreased to 47%, 46%, 45%, 45%, and 45%, respectively. L+TRA was temporarily interrupted in 3 pts and continued in 2 pts despite LVEF decrease. Per investigators, LVEF decrease resolved with no further sequelae in 4 pts (59%, 56%, 60%, and 50%) and was ongoing in 1 pt. Conclusion: Initial data indicate L+TRA or L+TRA with taxanes does not constitute a serious incremental cardiac risk and may not require more stringent cardiac monitoring than is used for A or TRA alone. The combined effect of HER2 inhibition with L+TRA appears not to increase the risk of CE in this population. No significant financial relationships to disclose.
Preoperative platelet-derived growth factor receptor inhibitor therapy combined with docetaxel and androgen ablation in high-risk localized prostate cancer
Authors: Mathew P. , Pettaway C. , Pisters L. , Williams D. , Troncoso P. , Logothetis C. 
Published: March 2020

5141 Background: Reduction in tumor interstitial fluid pressure with platelet-derived growth factor receptor (PDGFR) inhibitor therapy in experimental systems improves drug delivery and the therapeutic index of taxane chemotherapy (Pietras, Cancer Research, 2002). We hypothesized that PDGFR inhibitor therapy with imatinib mesylate combined with androgen ablation (AA) and docetaxel (D) induces pathological complete responses (pCR) in high-risk localized prostate adenocarcinoma (PC) prior to radical prostatectomy and pelvic lymph node dissection (RP). Methods: Thirty six men with PC ≥T2 disease or Gleason grade 8–10 or serum prostate-specific antigen (PSA) > 20 ng/ml or cT2b and PSA >10 ng/ml and Gleason 7 disease (AJCC, 1992), without radiological evidence of metastases, were planned to receive intramuscular leuprolide, imatinib 600mg orally daily, and weekly D 30 mg/m2 on D1, 8, 15, 22 q42 for three cycles (18 weeks) before RP [β (0.02, 1.98) prior on the possibility of pCR]. Unresectable pelvic nodal disease, post-operative PSA > 0.2 ng/ml or administration of post-operative radiation or AA were defined as treatment failure. Results: Between 6–03 and 9–04, 39 men were registered; median age 57 years (range, 44–71); 35 Caucasian, 2 Hispanic, 4 African-American. Risk factors included T3 disease (22/39), Gleason 8–10 disease (31/39), PSA > 20 ng/ml (12/39). Three men were ineligible or declined therapy; 29/36 (80%) received three cycles of therapy; 7/36 (20%) discontinued therapy related to toxicity. Grade 3–4 toxicity included rash (n=3), diarrhea (n=5), fatigue (n=3), neutropenia (n=2), hepatic (n=1). Severe or unexpected surgical complications were not encountered. No pCRs were defined; 15/36 (42%) have PSA < 0.2 ng/ml [12/36 (33%), <0.1 ng/ml] at 24 months and 13/36 (36%) met definition for treatment failure. Conclusions: The addition of the PDGFR inhibitor imatinib to pre-operative AA and D, although feasible, did not induce pCR in PC. [Table: see text]
Is age an independent predictor of clincially significant prostate cancer in a referral population? A case for needle biopsy in the elderly
Authors: Hanson G. , Wright J. , Kim J. , Borden L. S. , Porter C. R. 
Published: March 2020

5142 Background: Approximately 232,090 new cases of prostate cancer were diagnosed in the U.S. in 2005. As the population ages and life expectancy increases, physicians will increasingly be faced with patients in their 70’s who can be expected to live for greater than 10 years. Many of these patients are screened for prostate cancer and may ultimately be evaluated by a urologist. Clinically significant prostate cancer is still diagnosed in men in this age group. To address this issue, we evaluated a large prostate biopsy database to assess the nature of prostate cancer diagnosed in elderly men in a referral population. Methods: A prospective database of 790 men who had undergone biopsy by a single urologist (CRP) was reviewed. Demographic data was recorded. Patients with Gleason score 7–10 were defined as having clinically significant disease. Multivariate regression analysis was performed to determine the relationship of increasing age with higher Gleason scores (7–10) on biopsy. We divided our patients into clinically applicable age groups of greater than or equal to 70 and less than 70 years. Results: The mean age of patients was 63.1 years. Men over 70 years old were more likely to have increased mean prostatic volume (P < 0.001), abnormal DRE (P < 0.001) and presence of prostate cancer (P < 0.001). Patients aged 70 or older had more than a three-fold increased risk of Gleason 7 or greater cancer (OR 3.32, p <0.001). An abnormal DRE (OR 3.65, p<0.001) and PSA >10 (OR 4.05, p <0.001) were also independently associated with a statistically significant chance of detecting Gleason 7 or greater cancer. Conclusions: Age is an independent predictor of clinically significant prostate cancer in a referral population. Patients who are 70 years or older with a 10-year life expectancy should be counseled that they are at higher risk of harboring clinically significant prostate cancer and should therefore be considered for prostate needle biopsy. [Table: see text] No significant financial relationships to disclose.
What is the real impact of bone pain on survival of hormone-refractory prostate cancer (HRPC) patients treated with docetaxel?
Authors: Oudard S. , Banu E. , Medioni J. , Dionysopoulos D. , Cojocarasu O. , Banu A. 
Published: March 2020

5149 Background: Docetaxel is currently the standard of care for HRPC patients (pts). The moment of docetaxel initiation according to the presence or absence of the bone pain was less explored. Methods: Eligible HRPC pts were required to have a baseline bone pain evaluation using the rank-scores as follows: no pain or minimal pain (0), mild (1), moderate and severe pain (2), respectively. The main endpoint was to explore the overall survival (OS) impact of the bone pain (presence and intensity) using the Cox regression analysis, stratified by chemotherapy regimen. OS was calculated between start of chemotherapy and death or last follow-up for censored pts. Secondary endpoint was to evaluate the relationship between PSA doubling time (DT) and survival of pts with minimal or no pain. Results: Data of 145 consecutive HRPC pts treated in a single French center were analyzed. Chemotherapy was docetaxel (67%) or mitoxantrone-based. The median age was 68 years and 93% of pts had bone metastases, 55% with minimal or no pain at baseline. Median OS was 17.3 months (95% CI, 14.6–20) and 93% of pts died. There were OS differences between pain categories ( Table ). Pain intensity was significantly related with OS: hazard ratio=1.50 (95% CI, 1.20–1.88), P=0.0001 at the univariate analysis. Multivariate analysis adjusted by ECOG PS, hemoglobin and number of metastatic sites showed a 16% rise of the risk of death for pts with severe and mild pain. Pts with minimal or no pain at baseline have a different outcome depending of PSA DT (≥ 45 and < 45 days): median OS 32.4 months (95% CI, 16.2–48.7) and 16.5 months (95% CI, 10–22.9), respectively. Conclusions: Our results suggest that HRPC pts with minimal or without bone pain can experience a better OS with docetaxel-based therapy. This motivates the use of docetaxel early, before bone pain apparition. The OS benefit was even higher for asymptomatic pts with a longer PSA DT. [Table: see text] No significant financial relationships to disclose.
A prospective study of carboplatin-etoposide in docetaxel-pretreated patients with hormone-refractory prostate cancer (HRPC): Clinical activity and correlation with neuroendocrine features
Authors: Loriot Y. , Massard C. , Plantade A. , Escudier B. , Chauchereau A. , De Crevoisier R. , Fizazi K. 
Published: March 2020

5151 Background: There is currently no standard of care for patients (pts) with HRPC and disease progression after docetaxel-based chemotherapy. Platin compounds have demonstrated activity in this setting and in vitro evidence of synergy between carboplatin and etoposide has previously been reported. A significant proportion of advanced HRPC exhibit neuroendocrine features but there are limited data on whether these patients should be treated differently or not. Methods: Pts with HRPC who experienced failure after first-line docetaxel-based chemotherapy were prospectively treated with carboplatin (AUC 5 day 1) and etoposide (80 mg/m2 day 1 to 3), repeated every 3 weeks as second-line chemotherapy. The response rate (defined as a serum PSA decline of = 50%), progression-free survival (PFS) and overall survival (OS) were evaluated using consensus criteria (Bubley JCO 1999). Pain relief was evaluated using a visual analogic scale. Serum chromogranin A and neurone specific enolase (NSE) levels were measured at baseline. Toxicity was evaluated according to NCI criteria. Results: Forty-one HRPC pts, previously treated with docetaxel with (n=24) or without (n=17) estramustine, prospectively received carboplatin-etoposide as second-line chemotherapy. A PSA response was obtained in 9 pts (22%). Pain relief was achieved in 18 pts (45%). Median progression-free survival was 9 weeks and median overall survival was 19 months. Toxicity included grade 3–4 anemia in 25% and febrile neutropenia in 2%. Biological neuroendocrine features (e.g. elevated baseline serum chromogranin A and NSE) were not associated with response or PFS. The response rate was 18% and 31% in pts with normal and elevated baseline chromogranin A, respectively. Conclusions: The carboplatin-etoposide regimen is active and well-tolerated as second-line chemotherapy after docetaxel-based chemotherapy in HRPC patients. Activity was detected in both tumors with and without neuroendocrine features. No significant financial relationships to disclose.
Reasons for initial PSA (iPSA) and biochemical failure (BF) being poor predictors of prostate cancer (PC) mortality
Authors: Denham J. W. 
Published: March 2020

5153 Background: iPSA and BF are often poor predictors of mortality in men treated for locally advanced PC. We sought to find out why from prospective randomised trial data. Methods: In the TROG 96.01 trial men with T2b,c, 3, 4 N0 PC were randomised to 0, 3 or 6 months maximal androgen deprivation (AD) (goserelin 3.6 mg sc monthly and flutamide 250 mg po tid) prior to 66 Gy to the prostate and seminal vesicles. Failure site was diagnosed prior to salvage hormone therapy (ST) where possible, and type, timing and duration of response to ST recorded. Proportional hazards modeling was used to identify predictors of cause specific and overall survival (CSS, OS) at follow-up landmark points (where p>0.05=NS, <0.01=S, <0.001=H). Results: Between 1996 and 2000, 802 eligible men were randomised. Higher iPSA was found to be a potent predictor of BF (Houston [HF])H but a poor one for of CSSNS and OSNS. Patients having HF and/or clinical failure had unfavourable initial prognostic factors (high iPSAH, stageH, Gleason scoreH or risk groupH) compared to patients who did not fail. However in this cohort poor initial prognostic features did not predict PC death when the relapse characteristics (failure siteH and PSA doubling timeH [PSA DT]) were accounted for. Instead lower iPSA levels were predictive of worse outcome in these modelsS, a finding supported by univariate analyses. PSA DT was found to correlate positively with interval between HF and STH and the likelihoodS and duration of response to STH, and survivalH. Thus lower PSA DTs were associated with earlier intervention but poorer responses and outcomes. Conclusions: Prognosis after BF is related more to tumour biology at relapse than to initial prognostic factors. ST alone is an unsatisfactory treatment for rapid PSA DT relapses. No significant financial relationships to disclose.