bluuebunny/crossref_metadata_2025_split huggingface dataset:
C-reactive protein as a prognostic marker for men with androgen-independent prostate cancer (AIPC): Results from the ASCENT trial
Authors: Graff J. , Lalani A. S. , Lee S. , Curd J. G. , Henner W. D. , Ryan C. W. , Venner P. M. , Ruether J. D. , Chi K. N. , Beer T. M. ,   ASCENT Investigators
Published: March 2020

5074 Background: Concentrations of blood proteins such as PSA, hemoglobin (HGB), and LDH are associated with survival in men with AIPC. We sought to identify additional blood proteins associated with prognosis in chemotherapy-treated AIPC patients. Methods: Baseline plasma samples were stored (-80°C) from 160 patients enrolled in the ASCENT trial, a randomized placebo-controlled phase 2 trial comparing weekly docetaxel plus DN-101, an oral high-dose formulation of calcitriol, to weekly docetaxel. Multiplex immunoassays measured 16 cytokine/chemokine or cardiovascular/inflammation markers including IL-1a, IL-1β, IL-2, IL-6, IL-8, IL-10, TNFa, MCP-1, EGF, VEGF, PAI-1, MMP-9, sE-Selectin, sICAM-1, sVCAM-1 and C-reactive protein (CRP). Cox’s proportional hazard model was used to assess association between baseline biomarkers and survival or skeletal-related event (SRE)-free survival, and logistic regression for PSA Working Group Criteria response. Results: Baseline characteristics were similar to those of the 90 patients without samples, except for age (mean 68.0 vs. 70.6 yrs) and HGB (12.8 vs. 12.2 g/dL). CRP was the only biomarker that significantly predicted shorter overall survival (HR 1.41, 95% CI 1.20–1.65, p < 0.0001). When CRP (continuous) was entered into a multivariate model using 13 baseline variables (including PSA, LDH, alkaline phosphatase, HGB, ECOG Performance Status, age) only elevated CRP remained a significant predictor (p<0.0001) of shorter survival. When categorized as normal (= 8 mg/L) or abnormal (> 8 mg/L), elevated CRP was a significant predictor of shorter survival (HR 2.96 95% CI 1.52–5.77, p = 0.001) as was HGB (p=0.007). Elevated CRP was also associated with a lower probability of PSA response (OR 0.74, 95% CI 0.60–0.92, p = 0.007) and a shorter SRE-free survival (HR 1.30, 95% CI 1.15–1.48, p < 0.0001). Conclusions: Elevated levels of plasma CRP appear to be a strong predictor of poor survival and development of SREs in AIPC patients receiving docetaxel-based therapy. The use of CRP as a risk marker and its potential as a surrogate marker of treatment effect should be prospectively evaluated in future clinical trials in advanced prostate cancer. [Table: see text]
Phase II trial of pemetrexed disodium and gemcitabine in advanced carcinoma of the urothelium (E4802): A trial of the Eastern Cooperative Oncology Group
Authors: Li S. , Dreicer R. , Roth B. , Manoloa J. , Cooney M. , Wilding G. 
Published: March 2020

5079 Background: Advanced urothelial carcinoma is a moderately chemosensitive disease. Although the gemcitabine/cisplatin regimen has essentially replaced M-VAC as front-line therapy, both regimens are moderately toxic and produce similar response rates and median survival. Pemetrexed is a novel multi-targeted antifolate with single agent activity in advanced urothelial cancer. We evaluated pemetrexed in combination with gemcitabine in untreated pts with advanced urothelial cancer. Methods: Patients with TCC or mixed histologies received pemetrexed 500 mg/m2 IV over 10 minutes followed by gemcitabine 1,000 mg/ m2 IV over 30 minutes on day 1, with gemcitabine repeated on day 8 of a 21-day cycle. Dose reductions were mandated for grade 3/4 toxicities. Patients remained on treatment until disease progression or unacceptable toxicity or a maximum of 6 cycles of therapy. Standard RECIST criteria were used to assess response. Results: Total accrual was 46 pts. Two pts never started therapy and were excluded, leaving 44 pts included in the analysis. The pt cohort was 36 (82%) male and 42 (95%) Caucasian. Twenty-two pts (50%), 21 (48%) and 1 (2%) had 0, 1 and 2 MSKCC risk factors respectively. Seventy-five percent of pts had distant metastatic disease at study entry including 7 (16%) with liver, 3 (7%) bone and 14 (32%) lung metastases. A median of 4 cycles were administered (range, 1–6). The most common reasons for discontinuing treatment were progressive disease (27%) and toxicity (20%). Eighteen pts experienced grade 4 toxicities, including leukocytes (n=5), neutrophils (n=18), cardiac arrest, fatigue, infection with grade 3 or 4 neutropenia (n=1 pt each). Two pts died from grade 5 toxicities while receiving treatment: one death was from neutropenia and the other pt died from infection without neutropenia following sepsis and subsequent cardiac arrest. Response information is available for 39 pts. There has been 1 complete response and 10 partial responses with an overall response rate of 28% (90% CI: [17%, 42%]). Eleven pts had stable disease for at least 6 weeks. Conclusions: Pemetrexed/gemcitabine has modest activity in patients with previously untreated advanced TCC of the urothelium, but at the cost of significant toxicity. [Table: see text]
Outcomes of surveillance in unselected patients with clinical stage I testicular germ cell tumors: Results of a modern single institution series
Authors: Moore C. J. , Daneshmand S. , Hayes-Lattin B. , Stott W. , Nichols C. R. 
Published: March 2020

5085 Background: Orchiectomy is curative in 50–80% of patients (pts) with clinical stage I testicular germ cell cancer (CSITC) and modern chemotherapy at the time of relapse is nearly always curative. Traditional management in the US and Europe, which includes retroperitoneal lymph node dissection (RPLND) or adjuvant radiation or chemotherapy, imposes a significant treatment burden on all patients with CSITC. This study investigated outcomes of active surveillance in all pts with CSITC, with additional post-orchiectomy therapy reserved for only those pts who recur. Methods: Since 1998, Oregon Health & Science University’s institutional policy has been to recommend active surveillance alone to all CSITC pts after orchiectomy, independent of known risk factors. We retrospectively identified and reviewed the charts of 90 pts with CSITC treated between 1998 and 2006. Prognostic factors for relapse, time to relapse, post-orchiectomy treatment required, and overall survival rates were tabulated. Results: Of the 53 pts with CSI nonseminoma, complete data are currently available for 36. 12 (33%) relapsed at a median of 6 months (range 3–48) and all received 3 cycles of bleomycin, etoposide, and cisplatin (BEP). 2 pts (5.5% of total population) required RPLND post-chemotherapy for residual teratoma. No additional relapses have been seen, and all 36 pts are alive at a median follow-up of 51 months. Of 37 pts with CSI seminoma, complete data are available for 28. Seven pts (25%) experienced abdominal relapse, at a median of 10 months (range 3–14 months) after orchiectomy. All 7 pts were treated with abdominal radiation. Two pts subsequently relapsed and were cured with chemotherapy. All CSITC pts are alive without disease at a median follow-up of 60 months. Complete data on all 90 pts will be available this spring. Conclusion: This, the largest modern US series of surveillance alone after orchiectomy, resulted in uniformly excellent outcomes suggesting that primary active surveillance reduces the global burden of treatment for pts with CSITC and is appropriate for all pts with clinical stage I disease, independent of clinical risk factors or pathological subtype. No significant financial relationships to disclose.
The long term side effects of adjuvant carboplatin for stage 1 seminoma
Authors: Powles T. , Oliver T. , Ostrowski M. , Levay J. , Shamash J. , Williams M. 
Published: March 2020

5089 Background: Radiotherapy is associated with an increase of second cancer and cardiovascular disease. Because of difficulties in detecting recurrence on surveillance which can occur out to 10 years, this unit has developed Carboplatin as the treatment for these patients and this abstract summarises late events in these 3 cohorts. Methods: Radiation therapy consisted of para-aortic and pelvis treatment (3,000 cGy). This occurred between 1960 and 1978. Surveillance began in 1980 and Carboplatin studies in 1984 with 2 courses of 450 mg/m2 being standard until 1987 when 1 course AUC × 7 was introduced and with increased confidence became standard. Results: Seventy-eight patients were treated with radiotherapy (median follow up 17 years). Overall mortally was 24% at 20 years compared with expected 10%. Death from germ cell cancer was 4.0%, deaths from 2nd non-germ cell cancer were 13%, and deaths from other causes was 7.0%. For surveillance (n=110, median follow up 9.8 years) there were 1.7% deaths, with no germ cell or non-germ cell cancer related deaths., and 1.7% deaths due to non cancer. Carboplatin (n=186, median follow up 9.5 years 97>10 yrs, and 38 >15 yrs) was associated with 98% survival at 10 years with 0 deaths due to GCC (3% relapse all before 3 years) 1% due to second non-GCC cancer and 1% to other causes. Conclusion: The numbers of cases are too small to be absolutely confident of these figures. However, this data suggests there are no late relapses and no excess of cancer or cardiovascular deaths in the single agent carboplatin cohort. No significant financial relationships to disclose.
Phase II study of the angiogenesis inhibitor AZD2171 in first line, progressive, unresectable, advanced metastatic renal cell carcinoma (RCC): A trial of the PMH Phase II Consortium
Authors: Sridhar S. S. , Hotte S. J. , Mackenzie M. J. , Kollmannsberger C. , Haider M. A. , Pond G. R. , Chen E. X. , Srinivasan R. , Ivy S. P. , Moore M. J. 
Published: March 2020

5093 Background: AZD2171 is an oral, highly potent inhibitor of VEGFR1, VEGFR2, with activity also against cKit, PDGFRβ and Flt-4. We conducted a two-stage, phase II trial of AZD 2171 in first line advanced RCC, with a planned sample size of 37 pts, and a primary endpoint of tumor control rate (PR+SD). Methods: Pts had progressive, unresectable, advanced RCC, measurable disease, a performance status of ≤ 2 and no prior cytokine or antiangiogenic therapy. Pts received AZD2171 45 mg orally, daily, continuously (1cycle = 4wks) as monotherapy. Disease was evaluated with cross-sectional imaging every 8 wks. Functional DCE-MRI imaging was performed at baseline, 24h and 28d after the first dose. Pharmacokinetic studies were performed on day 8, 15 and 28. Results: From January- November 2006, 24 pts median (range) age 62 (44–80), were entered on study. Sixteen pts evaluable for response, 7 too early; 23 pts evaluable for toxicity; 1 pt inevaluable due to withdrawal. There have been 6 confirmed PR (6/16=38%), 1 unconfirmed PR, 5 SD, 4 PD. Tumor control rate 12/16=75%. Seventeen patients remain on treatment, 6 now off due to PD and 1 off due to consent withdrawal. Eighteen patients had dose reductions due to toxicity. Most common toxicities (any grade) were fatigue (21pts), voice alteration (14pts), hypertension (12pts), diarrhea (15pts), and increased creatinine (10pts). Common (>5% of cycles) grade 3+ adverse events were hypertension (5pts), joint pain (4pts), fatigue (7pts), dyspnea (2pts), increased ALT (2pts) and anorexia (3pts). Preliminary pK analysis is available on 6 patients: median (range) Tmax: 2hr (2- 6hr), Cmax: 107.8± 29.8 ng/ml, T1/2: 12.1 ± 2.2hr. Conclusion: AZD2171 is an active agent in first line, progressive, unresectable, advanced RCC with a partial response rate of 38% and tumor control rates of 75%. Accrual is ongoing with pharmacokinetics, functional imaging, and correlative studies. This agent warrants further investigation. No significant financial relationships to disclose.
The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Long-term outcomes in first-line patients (pts)
Authors: Ryan C. W. , Bukowski R. M. , Figlin R. A. , Knox J. J. , Hutson T. E. , Dutcher J. P. , George J. , Kirshner J. , Humphrey J. , Stadler W. M. 
Published: March 2020

5096 Background: Sorafenib (SOR) doubled median progression-free survival (PFS) versus placebo in a phase III study (TARGETs) for previously treated pts with clear cell renal cell carcinoma (RCC). We report on pts who had not received any prior systemic anti- cancer therapy (1st line) for advanced RCC from the ARCCS program in the US and Canada, which enrolled a broad range of pts. Methods: Pts received SOR 400 mg bid in the ARCCS open-label, nonrandomized treatment protocol if they were =15 years old with advanced (unresectable, recurrent or metastatic) RCC and had ECOG PS 0–2. In the US, ARCCS enrollment ended with SOR approval in 12/05, and pts were transitioned to commercial drug with 1st line pts being eligible for an additional 6-mo follow-up in an extension protocol (EP); Canadian enrollment completed in 8/06. Response evaluation (baseline and =1 post-baseline radiologic assessment) was conducted every 4 wks in the main study and every 8 wks during the EP. Pts without a confirmatory scan were classified as unconfirmed PR. The primary efficacy analysis on PFS was pre-specified to be performed only on the EP-enrolled pts. Results: Of the 2,488 pts valid for safety in ARCCS, nearly 50% were 1st line (n=1239) of which 69% were male with median age 65 yrs; 77% had prior nephrectomy and 29% had prior radiotherapy. Time from diagnoses to treatment was <1 yr for 52% and =1 yr 36% in these 1st line pts. Grade 3 and 4 adverse events with >2% incidence included hand-foot skin reaction 7.7%, fatigue 4.7%, hypertension 3.8%, rash/desquamation 5.2%, dehydration 2.9, diarrhea and dyspnea 2.6%. Confirmed responses are reported in the table ; 15% had unconfirmed PRs. For the 224 1st line pts enrolled in the EP, median PFS was 35.1 wks (95% CI; 32.7, 41.9). Conclusions: SOR toxicity in 1st line pts appeared similar to that in both overall and 2nd line populations previously reported in the phase III study. The PFS among patients enrolled in the EP is encouraging, but may be biased by low enrollment and selection for non-progressors. [Table: see text] [Table: see text]
Phase I trial of bevacizumab plus sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC)
Authors: Feldman D. R. , Kondagunta G. V. , Ronnen E. A. , Fischer P. , Chang R. , Baum M. , Ginsberg M. S. , Ishill N. , Patil S. , Motzer R. J. 
Published: March 2020

5099 Background: Bevacizumab, an intravenous monoclonal antibody against VEGF, and sunitinib, an oral multi-targeted tyrosine kinase inhibitor of VEGF and PDGF receptors, both have activity in mRCC [NEJM 349:427–434; JAMA 295:2516–2524]. Combining bevacizumab and sunitinib may increase antitumor efficacy by maximizing inhibition of the VEGF pathway. The safety and maximum tolerated dose (MTD) of sunitinib in combination with bevacizumab was assessed in this Phase I trial. Methods: Cohorts of 3–6 pts with mRCC received escalating doses of sunitinib (dose levels: 25, 37.5, and 50 mg po) daily for 4 weeks (wks) followed by 2 wks off with fixed- dose bevacizumab (10 mg/kg iv) every 2 wks continuously. Pre-determined dose-limiting toxicities (DLTs) in the first 6-wk cycle included Grade (Gr) 4 neutropenia, ≥Gr 3 thrombocytopenia of ≥7 days, Gr 4 hypertension or proteinuria, and other Gr 3 non-hematologic toxicity of ≥7 days. Pts who came off study prior to completion of cycle 1 for any reason other than a DLT were replaced. Serum VEGF levels were measured before and during cycles 1 and 2. Results: 16 pts (11 male, 5 female, median age 57) were enrolled. Of 8 patients entered at the first dose level (sunitinib 25 mg, bevacizumab 10 mg/kg), 2 were replaced; 1 never received treatment and 1 did not complete cycle 1 due to rapid progression of disease (PD). No DLTs occurred in the remaining 6 evaluable pts in this cohort. At the 2nd dose level (n =6, sunitinib 37.5 mg, bevacizumab 10 mg/kg), 1 pt receiving low molecular weight heparin had a DLT of Gr 4 hemorrhage. 2 pts have enrolled in the 3rd dose level (sunitinib 50 mg, bevacizumab 10 mg/kg) but are not yet evaluable for toxicity or response. Gr 3/4 toxicities over all cycles included Gr 3 hypertension (n=4), Gr 3 proteinuria (n=2), Gr 3 abdominal pain (n=2), Gr 4 hemorrhage (n=1), and Gr 3 hand/foot syndrome (n=1). 13 pts were evaluated for best response–4 had partial responses, 7 had stable disease, and 2 had PD. Serum VEGF levels decreased during cycle 1 in all pts. Conclusions: The combination of sunitinib and bevacizumab in mRCC pts was tolerable at the first 2 dose levels. Once the MTD is identified, further testing of this combination in phase II trials may be indicated for mRCC as well as other malignancies. [Table: see text]
Phase II ECOG trial of atrasentan in advanced renal cell carcinoma
Authors: Manola J. , Carducci M. , Nair S. , Liu G. , Rousey S. , Wilding G. 
Published: March 2020

5102 Background: Atrasentan, an oral selective endothelin A receptor antagonist, demonstrated activity in patients with RCC included in Phase I studies. Based on these preliminary findings, a phase II study was undertaken in patients with measurable or nonmeasurable (bone only) metastatic RCC. Methods: Patients with locally recurrent or metastatic disease were stratified on disease status (measurable or bone only metastases) and prior immunotherapy. Eligible patients also had no prior chemotherapy, no more than 1 prior immunotherapy, and ECOG PS 0, 1, or 2. Prior nephrectomy was permitted. Patients received atrasentan 10 mg/day po until progression or unacceptable toxicity. Standard RECIST criteria were used to assess response. The primary endpoint was the progression-free rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A two-stage design was used for cohorts with no prior immunotherapy. Results: Between July 2003 and July 2005, 98 patients were registered. Four patients were ineligible and 1 withdrew before treatment. Median duration of treatment was 10 weeks (range, 2 to 107 weeks). Toxicities were mild, with 73% of patients reporting no Grade 3 or higher treatment- related adverse events. Grade 4 adverse events included neutropenia (n=3), dyspnea (n=2), thrombosis and supraventricular arrhythmia (n=1 each). Six-month progression-free rates (90% CI) were 14% (6 - 25%), 0% (0 - 39%), 12% (3 - 28%) and 17% (5 - 38%) respectively for patients with prior immunotherapy and measurable disease (n=44), prior immunotherapy and bone metastases only (n=6), no prior immunotherapy and measurable disease (n=25), and no prior immunotherapy and bone metastases only (n=18). Median progression-free survival was 2.3 months (95% CI, 2.0 - 3.5 months). Conclusions: While well-tolerated, atrasentan did not yield 6-month progression-free rates that would support its use as first-line monotherapy in patients with advanced RCC. No significant financial relationships to disclose.
Benefit from adjuvant trastuzumab may not be confined to patients with IHC 3+ and/or FISH-positive tumors: Central testing results from NSABP B-31
Authors: Paik S. , Kim C. , Jeong J. , Geyer C. E. , Romond E. H. , Mejia-Mejia O. , Mamounas E. P. , Wickerham D. , Costantino J. P. , Wolmark N. 
Published: March 2020

511 Background: Trastuzumab is a humanized monoclonal antibody targeted to HER2 protein and currently indicated for HER2-positive breast cancer defined by overexpression of HER2 protein (3+ IHC staining by HercepTest™) or HER2 gene amplification (HER2/CEP17 ratio over 2 by PathVysion® FISH assay). These criteria were determined for advanced disease but have not been formally tested in the adjuvant setting. We examined these tests’ ability to predict benefit from adjuvant trastuzumab in NSABP trial B-31. Methods: All available tumor tissue blocks from the B-31 trial were subjected to HercepTest and PathVysion assay as defined in the B-31 protocol. Formal statistical test of interaction between HER2 levels measured by these two tests and benefit from trastuzumab was performed. Results: 207 of 1,795 cases (11.5%) showed gene amplification as determined by PathVysion, and 255 of 1,662 (15.3 %) showed overexpression as determined by HercepTest. 161 of 1,662 (9.7%) had neither gene amplification nor overexpression. There was a consistent benefit from trastuzumab in every subset defined by IHC or FISH. No statistical interaction was found between DFS benefit from trastuzumab and levels of protein (p=0.26) or HER2 gene copy number (p=0.60). Benefit was observed in patients with tumors that were negative for FISH and had less than 3+ staining intensity on IHC by HercepTest (RR=0.36 [CI: 0.14–0.92] p=0.032). Conclusion: Current definition of HER2 overexpression/gene amplification based on data from advanced disease may need to be modified for the adjuvant setting. [Table: see text] No significant financial relationships to disclose.
A validation/evaluation of five postoperative prognostic tools for prostate cancer
Authors: Inman B. A. , Leibovich B. C. , Siddiqui S. A. , Frank I. 
Published: March 2020

5117 Background: Prognostic nomograms, scoring tools, and risk tables are rapidly accumulating in the prostate cancer (PCa) literature. It is not always clear to whom these tools should apply and how well they predict the outcomes they were designed to forecast. There is need for independent evaluation of these tools. Methods: We used the Mayo Clinic Radical Prostatectomy Registry, a prospective database of radical prostatectomy (RP) outcomes, to assess tools designed to predict RP outcomes. The validation set included 13,313 RP patients from 1990–2005. There were 3,256 PSA failures, 566 metastases, and 1,599 deaths (301 were due to PCa). We assessed the discrimination, calibration and overall accuracy of prediction tools identified through a structured Pubmed search. Results: Tools varied greatly in terms of complexity, width of prediction interval, and method of presentation. Several tools included non-standard variables and were therefore unevaluable, despite an extensive dataset, leaving the 1999 and 2005 Kattan nomograms, the 1998 and 2001 CDPR scores, and the 2001 GPSM score for analysis. Discrimination (quantitated by the c index) was better for PCa-specific survival and metastases than for PSA failure ( Table ). Kaplan-Meier plots demonstrated clustering of risk groups in most tools, most severely in the higher risk groups of the Kattan nomograms. The calibration plots of most tools (excepting GPSM) had a serious discordance between observed and predicted outcomes in the lower probability ranges. This meant that most tools gravely overestimated the probability of RP failure in high-risk patients, by up to 4- fold. Conclusions: The tools showed moderate discriminatory ability for PSA failure but performed much better for non-surrogate outcomes. Most tools (excepting GPSM) were miscalibrated in high risk patients and dramatically underestimated the efficacy of surgery in this cohort. Prognostic tools may not be as accurate as previously reported. [Table: see text] No significant financial relationships to disclose.