bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effective analysis between enzalutamide and abiraterone in the treatment of metastatic castration-resistant prostate cancer.
Authors: Chopra Akhil , Haaland Benjamin , Lopes Gilberto 
Published: February 2017

217 Background: Recently Abiraterone (A) and Enzalutamide (E), new drugs with different novel mechanisms of action, have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) based on the COU-AA-301 and AFFIRM phase III trials, after docetaxel failure. The lack of direct comparative trials has introduced a new treatment dilemma for the practicing oncologist: is one drug more effective than the other? Methods: We performed an indirect comparative effectiveness analysis between E and A using the results of the AFFIRM and COU-AA-301 pivotal trials. Due to the lack of study-to-study replication of comparisons, these indirect comparisons are subject to the assumption that the relative effects of each drug relative to placebo are the same across studies. Results: 1) Overall survival (OS)- the respective hazard ratios (95% confidence intervals {CI}) in the AFFIRM and COU-AA-301 trials for OS for E vs. placebo and A vs. placebo were 0.63 (0.53-0.75) and 0.66 (0.56-0.79). The indirect estimate of the hazard ratio (HR) (95% CI; p-value) for E vs. A was 0.96 (0.75-1.22; 0.72) 2) Time to PSA progression- the respective HR(95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 0.25 (0.20-0.30) and 0.58 (0.46-0.73). The indirect estimate of the HR (95% CI; p-value) for E vs. A was 0.43 (0.32-0.58; 4.3 × 10-8). 3) Radiographic progression Free Survival (rPFS)- The respective HR (95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 0.40 (0.35-0.47) and 0.67 (0.59-0.78). The indirect estimate of the HR (95% CI; p-value) for E vs. A was 0.60 (0.49-0.74; 7.1 × 10-7). 4) PSA response- the respective odds ratios (95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 77.08 (34.02-174.70) and 5.49 (3.84-7.84). The indirect estimate of the odds ratio (95% CI; p-value) for E vs. A was 14.04 (5.75-34.28; 6.6 × 10-9). Conclusions: In this indirect comparative effectiveness analysis, E appears to be more effective than A in terms of time to PSA progression, rPFS and PSA response. OS was not different.
Phase I results from a study of lapatinib with gemcitabine and cisplatin (GC) in advanced/metastatic bladder cancer.
Authors: Daugaard Gedske , Sengeløv Lisa , Agerbaek Mads , Sternberg Cora N. , Van Herpen Carla , Collette Sandra , Marreaud Sandrine ,   European Organisation for Research and Treatment of Cancer
Published: February 2017

252 Background: Lapatinib (Tykerb, Tyverb) is a potent EGFR and ErbB2 inhibitor approved for the treatment of breast cancer. GC is a standard chemotherapy regimen for advanced/metastatic bladder cancer and there are preclinical and clinical data suggesting the role of EGFR and HER2 in urothelial carcinoma. This phase I study examined the safety of lapatinib in combination with GC in patients (pts) with bladder cancer. Methods: The primary phase I objective was to determine the maximum tolerated dose of lapatinib 750–1,250 mg that could be administered safely with GC in bladder cancer pts. A 3+3 dose escalation was used with lapatinib 750 mg, 1000 mg and then 1250 mg. Lapatinib was dosed daily and G (1000 mg/m² days 1, 8, 15) + C (70 mg/m² day 2) every 28 days. Results: 18 pts with median age 63 yrs (range 50-77) and ECOG PS 0/1 (66.7% with WHO-PS 0 and 33.3% with WHO-PS 1) were included. 3/6, 3/5 and 6/7 pts completed at least one cycle according to the protocol and received lapatinib 750 mg, 1000 mg and 1250 mg + GC, in cohorts 1, 2 and 3, respectively. No dose-limiting toxicities (DLTs) occurred in cohort 1 or 2 (3 pts each); in cohort 3 (2 x 3 pts), 1 of 6 pts had DLT (Gr4 related febrile neutropenia and renal failure). One discontinued due to pt decision after 1 cycle. Ten pts received 6 cycles and one 7 cycles. The response rate among the 11/12 eligible patients was 73% (1 CR, 7 PR, 3 SD and 1 not assessable). Further toxicity data together with responses in relation to EGFR and HER2 status will be presented. Conclusions: Within the limits of a phase I study, lapatinib 750–1,250 mg + GC appears safe and tolerable with considerable activity at the maximum planned dose in bladder cancer. Clinical trial information: NCT00623064.
Micropapillary bladder cancer: Stage at presentation and treatment outcome—Analysis of 121 patients from a cancer database.
Authors: Holyoak Joshua D. , Panfili Zachary , Kiran Ravi P. , Pokala Naveen 
Published: February 2017

289 Background: The micropapillary variant of transitional cell cancer(MPTCC) is an aggressive pathological subtype of bladder cancer and radical cystectomy is recommended for patients with non−muscle invasive disease. This study compares the treatment patterns and survival outcome in 121 patients. Methods: Patients with MPTCC (code 8131) were identified from the Surveillance Epidemiology and End Results (SEER 17) database. Data was analyzed for demographics, stage, treatment, overall (OS) and cancer specific survival (CSS). Appropriate statistical tests were used. Results: 121 patients were identified (2001−08). Mean age was 73.3 years, 76.9% were male (76.9%, n=93), 82.7% were Caucasian. 40.5% (n=49) had non−muscle invasive (NMI) disease and 59.5% had muscle−invasive disease (MI) at diagnosis. The T stage was Ta or Tis (n=17), T1 (n=32), T2 (n=38) T3 (n=20) and T4 (n=14). 23 patients had node positive disease, the nodal status was not known in 4 patients. 10 patients had distant metastasis. Surgical procedures performed include, TURBT (n=83), Radical cystectomy (n=34), pelvic exenteration (n=1) and partial cystectomy (n=3). 8 patients received post−operative radiotherapy. The mean OS was 64.9, 42.9, 16.1 and 50.2 months and the mean CSS was 81.2, 56.3, 15.7 and 64.4 months for NMI, MI, distant and the whole group respectively. The 5−year OS was 40%, 54% and 34% and the 5 year CSS was 62%, 53% and 82% for the whole group, MI and NMI respectively. All patients with distant disease were dead by 28 months. On analysis of CSS by treatment type the 5−yr CSS for NMI was 81% (n=36) after TURBT and 100% (n=3) after Radical surgery. For MI disease the 3−yr CSS was 66% after TURBT (n=18) and the 5−yr CSS was 54% after radical surgery (n=29). On multivariate analysis, higher stage and age were associated with worse survival. TURBT was associated with better survival. Conclusions: MPTCC is a rare variant of TCC. 81% survival can be achieved with TURBT for non-muscle invasive MPTCC.
A phase I/II study of safety and efficacy of orteronel (TAK-700), an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC): Updated phase II results.
Authors: Petrylak Daniel , Gandhi Jitendra G. , Clark William R. , Heath Elisabeth I. , Lin Jianqing , Oh William K. , Agus David B. , Carthon Bradley Curtis , Moran Susan , Kong Ning , Suri Ajit , Bargfrede Michael , Liu Glenn 
Published: February 2017

59 Background: Orteronel is an investigational non-steroidal, selective inhibitor of 17,20-lyase, a key enzyme in the production of steroidal hormones. DP is currently an approved therapy in mCRPC; this phase 1/2 study examined orteronel + DP in men with mCRPC. Methods: Castrate men (testosterone [T] <50 ng/dL) with mCRPC, no prior chemotherapy and no ketoconazole/abiraterone received orteronel (400 mg BID) + D (75 mg/m2 q3w) + P (5 mg BID). The primary phase 2 objectives were tolerability, PK, serum PSA declines, and best PSA response. Secondary objectives included time to progression of PSA ± radiographic disease, response by RECIST 1.1. Results: At data cutoff (July 23, 2012), 24 men had been treated and 12 remained on study: median age was 66 yrs (n=24, range 53–87), ECOG PS 0/1 (88%/13%). At baseline, median PSA was 46 ng/mL (4.5–813) and T was 6.8 ng/dL (2.6–13.8). 9 men discontinued due to AEs (the most common was fatigue [13%]). All men reported at least 1 Gr ≥3 AE (23 were drug-related). Drug-related Gr ≥3 AEs ≥10% were neutropenia (38%); WBC decreased (25%); fatigue (21%); decreased neutrophil count (17%); blood alkaline phosphatase increased, and leukopenia (each 13%). The most common drug-related SAE was dehydration (13%). There were 2 on-study deaths, due to disease progression and respiratory distress, both considered unrelated to treatment. At 3 mo, PSA response was evaluable in 18 men; PSA30/50/90 rates were 83%/72%/28%. Best PSA decline (median) was -76% (n=23; -99 to +144%). Median T at 3 mo decreased to ≤0.2 ng/dL (0.3–10.6). Response was evaluable in 9 men; 5 achieved a PR; ORR was 56% (n=9; 80% CI: 30, 79). Median time to PSA progression was 6.1 mo (95% CI: 4.6, not reached); median time to radiologic progression was not reached. The Cmax of orteronel + DP was similar to that of DP alone with no evidence of DDI. Conclusions: Orteronel 400 mg BID + DP appears tolerable and shows androgen-lowering activity, and strong PSA and partial tumor response in mCRPC. There was no evidence of DDI between orteronel and DP. Updated data, including a detailed PK analysis, will be presented. Clinical trial information: NCT01084655.
Adjuvant gemcitabine plus docetaxel followed by 5FU chemoradiation for patients with resected pancreaticobiliary cancers: A single institution phase II study.
Authors: Cho May , Wang-Gillam Andrea , Gao Feng , Linehan David , Hawkins William G. , Suresh Rama , Fournier Chloe , Picus Joel , Tan Benjamin ,   GI02
Published: February 2017

325 Background: Adjuvant chemotherapy with Gemcitabine for six months has improved overall survival (OS) in resected pancreatic cancer compared to observation alone. The RTOG study showed adding gemcitabine to 5FU chemoradiation therapy showed improved OS in pancreatic head cancer patients. We evaluated the feasibility and safety of adjuvant gemcitabine plus docetaxel followed by radiation with 5FU after curative resection of pancreatic and biliary adenocarcinomas at our institution. Methods: Patients with resected pancreaticobiliary cancers were treated with 2 cycles of gemcitabine with docetaxel. Infusional 5FU at was given with 3-D conformal external beam radiation followed 4 weeks later by 2 more cycles of gemcitabine plus docetaxel. The primary objective was to evaluate the feasibility and safety of this regimen with the secondary aims to describe the toxicities, disease-free (DFS) and overall survival (OS) in these patients. Results: 50 patients were enrolled in the study. Median age was 59 with M;F ratio of 1:1.4 and 12% African-American. 30 patients had pancreatic cancer, 8 patients had ampullary cancer and 12 patients had gallbladder cancers. 30 patients completed all therapy. 4 patients withdrew the study due to non-medically related reasons. 7 patients had early disease recurrence. 6 patients withdrew consent due to side effects. 2 were taken off study after developing infection and 1 patient died of viral pneumonia leading into ARDS. Grade 3-4 Non-hematologic toxicities include diarrhea (12%), fatigue (4%), renal failure (2%), hepatic toxicity (4%). Grade 3-4 hematologic toxicities include neutropenia (30%), anemia (2%) and thrombocytopenia (10%). The median OS and DFS in pancreatic cancer is 17 and 9 months. The OS and DFS in ampullary cancer and gallbladder cancer is 27 and 14.4 months respectively. Conclusions: Adjuvant gemcitabine plus docetaxel followed by concurrent 5FU-CRT is feasible and tolerable. However, outcomes for pancreatic cancer patients appeared to be inferior compared to CONKO and RTOG studies. This regimen may be a reasonable adjuvant option for high risk biliary tract cancers. Clinical trial information: NCT00660699.
Assessment of IL-6, IL-8, bFGF, PDGF-BB, and VEGF-A as prognostic and predictive biomarkers for anti-VEGF in metastatic colorectal cancer (mCRC).
Authors: Price Timothy Jay , Townsend Amanda Rose , Bruhn Maressa , Lee Chee , Wrin Joe , Shivasami Aravind , Arentz Georgia , Tebbutt Niall C. , Cunningham David , Hardingham Jenny ,   Australasian Gastrointestinal Trials Group
Published: February 2017

502 Background: There remains a need for predictive biomarkers in mCRC to better identify patients who clinically benefit from anti-VEGF therapy, in particular bevacizumab (BEV). The AGITG MAX trial compared capecitabine (C) with capecitabine (+/- mitomycin C (M)) and BEV and PFS was superior in the CB+/-M arm. Here we have taken a panel of pro-angiogenic proteins to assess whether there is a signal for a predictive factor for bevacizumab outcome in the MAX trial tissue population (TTP). Methods: Protein was isolated from FFPE tumour tissue and assayed using custom Bio-plex arrays to assess the expression levels of candidate tumour biomarkers IL-6, IL-8, bFGF, PDGF-BB and VEGF-A. As there are no accepted cutoff points for these analytes we chose the medians of distribution of each of these biomarkers as cutoff points for dichotomization into “high” v “low”. We then correlated levels of the biomarkers with objective response rate, disease-free and overall survival. Results: Total protein was isolated from FFPE tumour sections from 41.5% of patients (n=196) recruited into the MAX clinical trial and assayed for the proteins using a multiplex platform. Patients were generally balanced, tumour tissue population v intention to treat. Median follow up time is 30.2 mths. For patients receiving BEV there was no relationship between the level of IL-6, IL-8, bFGF, PDGF-BB and VEGF-A and PFS and OS. In patients treated with BEV/C vs. C alone, low tumor VEGF-A was predictive of better ORR as compared to those with a high level (ORR 53% vs 38%, p = 0.03). Multivariate analyses showed low VEGF-A expression level was a significant prognostic factor for longer progression free survival (median PFS 9.3 months low VEGF-A v 7.2 months high VEGF-A, multivariate adjusted HR 1.55 (95% CI 1.12-2.13), p = 0.008). Conclusions: We have shown that the chosen panel of pro-angiogenic proteins was not predictive for PFS or OS outcomes when B is added to C in mCRC. However low VEGF-A level did predict for higher ORR and was an independent prognostic marker for PFS in this cohort.
Association of PTEN protein loss with upgrading of prostate cancer from biopsy to radical prostatectomy.
Authors: Carvalho Filipe LF , Lotan Tamara L , Peskoe Sarah B. , Hicks Jessica , Good Jennifer , Fedor Helen L. , Humphreys Elizabeth B , Han Misop , Platz Elizabeth , Squire Jeremy , DeMarzo Angelo , Berman David M. 
Published: February 2017

127 Background: Active surveillance is increasingly recommended for men with low-risk Gleason Score 3+3=6 (GS 6) prostate cancer. Yet, approximately one-third of patients with GS 6 cancer on biopsy are upgraded to higher GS at radical prostatectomy (RP). Previous studies have shown that clinical-pathologic parameters (age, prostate-specific antigen [PSA], prostate volume, extent of disease) are weak predictors of GS6 tumor upgrade. Our goal was to investigate the utility of PTEN as a molecular marker to predict upgrading in GS 6 biopsies. Methods: In a retrospective case-control study, 71 patients with GS 6 tumors on needle biopsy that were upgraded to GS 7 or higher cancer at RP (cases) were compared to 103 patients whose GS 6 tumors on needle biopsy were not upgraded at RP (controls). The most extensively involved needle core biopsy from each case was immunostained and scored for PTEN protein loss using a previously validated immunohistochemical (IHC) assay and binary scoring system. Confirmatory fluorescence in situ hybridization (FISH) was used to assess for PTEN gene deletion in biopsies with PTEN protein loss. The correlation of upgrading with PTEN loss and with clinical-pathologic variables was assessed by logistic regression. Results: Patients with upgraded cancers were older than controls (61.8 vs. 59.3 years), had higher mean pre-operative PSA levels (6.53 vs. 5.26 ng/mL), and a higher fraction of biopsy cores involved by tumor (0.42 vs, 0.36). However, of all pathologic variables, PTEN protein loss by IHC was most predictive of upgrading. Overall, PTEN protein loss was found in 18.3% (13 out of 71) of upgraded cases compared to 6.8% (7 out of 103) of controls (p=0.02). In the cases with PTEN protein loss, FISH confirmed homozygous PTEN deletion in 90% (9 out of 10) of upgraded tumors compared to 67% (4 out of 6) of interpretable not upgraded controls. On multivariate analyses, even after adjusting for age, preoperative PSA, clinical stage and race, GS 6 tumors with PTEN protein loss on biopsy were significantly more likely to be upgraded at RP compared to those without PTEN loss with odds ratio (OR) = 3.04 (1.08-8.55; p=0.035). Conclusions: In prostate needle biopsies, PTEN IHC may help distinguish men with low risk cancer from men with intermediate or higher risk cancers.
Feasibility of docetaxel-prednisone (DP) in frail elderly (age 75 and older) patients with castration-resistant metastatic prostate cancer (CRMPC): GERICO10-GETUG P03 trial led by Unicancer.
Authors: Mourey Loic , Gravis Gwenaelle , Sevin Emmanuel , Priou Frank , Bompas Emmanuelle , Sarda Corinne , Houede Nadine , Carola Elisabeth , Abadie Lacourtoisie Sophie , Latorzeff Igor , Orsini Christine , Filleron Thomas 
Published: February 2017

152 Background: Chemotherapy with docetaxel-prednisone (DP) is one of the standard treatment of castration-resistant metastatic prostate cancer (CRMPC). However little is known about feasibility of DP in frail elderly patients seen in daily practice. Methods: Randomized phase II study evaluating prospectively the feasibility of DP administered either q3w (Arm A: 60 mg/m² cycle one then 70 mg/m²) or weekly (Arm B: 35 mg/m² D1 D8 q3w) in patients age 75 or older, assessed through comprehensive geriatric assessment (CGA) and classified according to the International Society of Geriatric Oncology (SIOG) as vulnerable (SIOG group 2) or frail (SIOG group 3). Failure was defined as: (1) stop or delay of chemotherapy more than 2 weeks, (2) need for dose reduction more than 25%, (3) febrile neutropenia or NCI CTC grade 3 non-haematological toxicity (excluding alopecia), and (4) decrease of activities of daily living (ADL) scoring two or more points. The study was based on a Simon’s optimum two-stage design for each group (α = 5%, 1-β = 90 %, p0 = 0.70 and p1 = 0.90). An interim analysis was planned after enrolment of 15 patients per arm, with continuation of the program if at least 12 patients met the feasibility criteria. Results: From December 2010 to August 2012, 21 centers have included 66 CRMPC patients, 45 and 21 in SIOG groups 2 and 3 respectively, based on investigators evaluation. The planned interim analysis primary endpoint is based on group allocation by a steering committee (per-protocol [PP] population). The enrolment in group 3 was prematurely closed on October 2012 after inclusion of 19 PP patients (Arm A/B, n=9/10) on recommendation of a safety committee due to an excess of toxic deaths. In this group, only four patients completed six cycles of DP in each arm. In group 2, the planned interim analysis was performed after inclusion of 30 PP patients (Arm A/B n=15/15): 11 and 10 patients in Arm A and B did not meet the predefined criteria for feasibility (73.3%; 95%CI=[44.9; 92.2] and 66.6%; 95%CI=[38.4; 88.2], respectively, and only nine and seven respectively completed six cycles of DP. Conclusions: Chemotherapy with DP given q3w or weekly is not feasible in CRMPC patients age 75 and older classified in SIOG group 2 and 3, according to our study criteria. Patients age 75 and older shouldn’t be offered DP without a CGA. Clinical trial information: NCT01254513.
Treatment patterns in patients with recurrent high-risk bladder cancer.
Authors: Ballon-Landa Eric Christian , Chamie Karim , Bassett Jeffrey C. , Daskivich Timothy J. , Lai Julie , Hanley Janet , Konety Badrinath R. , Litwin Mark S. , Saigal Christopher ,   The Urologic Diseases in America Project
Published: February 2017

303 Background: Patients with high-risk bladder cancer are apt to develop multiple recurrences. Since the association of recurrences with aggressive treatment in individuals with recurrent high-grade disease has not been quantified, we sought to determine whether increasing number of recurrences correlates with higher treatment rates. Methods: Using linked SEER-Medicare data, we identified subjects with recurrent high-grade, non-muscle-invasive disease diagnosed in 1992–2002 and followed until 2007. Using propensity score and competing-risks regression analyses, we quantified the incidence of radical cystectomy, radiotherapy, and systemic chemotherapy after each recurrence. We further restricted our analyses of treatment in auspicious environments, defined as those patients most suited for aggressive intervention: age <70, Charlson 0, and undifferentiated T1 tumors treated at academic cancer centers. Results: Of 4,521 subjects, (59.6%) 2,694 recurred more than once within two years of diagnosis. Compared with patients who only had one recurrence, those with ≥4 recurrences were less likely to undergo radical cystectomy (9.7% vs 12.1%, p value=0.03), but more likely to undergo radiotherapy (18.0% vs 12.1%, p value<0.01) and systemic chemotherapy (6.7% vs 4.2%, p value<0.01). For patients with ≥4 recurrences, only 25% were treated with curative intent, while 43% were similarly treated in auspicious environments. Conclusions: Only 25% of patients with high-risk bladder cancer who recur ≥4 times undergo treatment for curative intent. Increasing recurrences do not appear to alter the treatment course, as patients and their doctors may be unable or unwilling to proceed with aggressive treatment despite mounting risk of disease progression. [Table: see text]