bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension and cardiotoxicity in metastatic renal cell carcinoma (mRCC) treated with sunitinib (SU).
Authors: Prati Veronica , Ortega Cinzia , Ballatore Valentina , Galizia Danilo , Ruatta Fiorella , Bonzano Alessandro , Aliberti Sandra , Grignani Giovanni , Aglietta Massimo 
Published: March 2020

e15073 Background: Recent data have shown that cardiotoxicity (CHFcongestive heart failure, CADcoronary artery disease)could be an important side-effect in patients (pts) with RCC treated with tyrosine kinase inhibitors (TKIs). LVEF(Left ventricular ejection fraction)reduction may occur in up to 10% of pts treated with SU and uncontrolled hypertension could worse this side-effect. This complication is reversible with TKI interruption and appropriate antihypertensive therapy. Methods: We have prospectively analyzed patients receiving SU as a first-line treatment for mRCC. Between April 2007 and December 2011,31 consecutive pts, median age 67 yrs (41-80) were treated with SU at the standard dose of 50 mg/day,4 weeks on and 2 weeks off. We recorded for all pts CAD risk factors, preexisting hypertension,rhythm disturbances and heart failure. ECG, echocardiography and cardiology consultation were performed at baseline, and every three months until progression or permanent SU discontinuation. We searched correlations between cardiotoxicity onset and hypertension. Results were assessed with paired Student’s t-test and Chi-square test. Results: At baseline,we found 22 pts (71%) with hypertensive disease (HD). The median duration treatment was 8,3 months(22-0,4).On TKI therapy 6/22 pts (27.2%) worsened the preexisting HD, which was controlled with adequate treatment according to American Heart Association guidelines, without determining treatment discontinuation. Furthermore 6/31 pts (19%) developed this adverse event. In 14/31 pts (45%) we showed a median ≥ 10% LVEF reduction compared to baseline value (p=.001); 13/31 pts were asymptomatic and only one presented symptoms of CHF and discontinued the treatment. In this study, history of HD,worsening of preexisting HD or development of HD are not predictive for >10% LVEF reduction (p=ns). Conclusions: In pts with mRCC receiving SU as a first-line treatment, HD is not predictive for LVEF reduction. Moreover on TKI therapy there is a statistically significant LVEF reduction, but this adverse event does not determine a treatment discontinuation. A cardiovascular monitoring during SU treatment may reduce this event in order to allow an adequate treatment.
Comparative efficacy of sunitinib versus sorafenib as the first-line treatment for patients with metastatic renal cell carcinoma.
Authors: Park Seongjoon , Lee Jae-Lyun , Park Inkeun , Park Kwonoh , Ahn Yongchel , Ahn Jin-Hee , Lee Dae Ho , Song Cheryn , Hong Jun Hyuk , Kim Choung-Soo , Ahn Hanjong 
Published: March 2020

e15080 Background: Currently, sunitinib has been recommended as the primary treatment in the patients with metastatic renal cell carcinoma (mRCC) among the vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). However, there are no published clinical data that compared directly the efficacy of targeted agents in the first line setting, and first-line treatment in mRCC patients is yet to be determined. Methods: To compare the efficacy and toxicities between sorafenib and sunitinb, clinical database was used to identify all patients with mRCC treated with VEGF TKIs in Asan Medical Center from April 2005 to March 2011. Among 304 patients, we identified 49 and 220 patients who were treated first with sorafenib and sunitinib, respectively. Results: The patients in the sorafenib group were older than those in the sunitinib group (62 vs 56.5 years, p=0.019). Disease control rate (DCR) of 82% was achieved in both groups. After a median follow-up duration of 49 months, progression free survival (PFS) and overall survival (OS) were not significantly different (sorafenib vs sunitinib, PFS; 8.6 months vs 9.9 months, p=0.948, OS; 25.7 months and 22.6 months, p=0.774). The patients treated with sorafenib have required dose reduction due to toxicities less frequently than those treated with sunitinib (37% vs 54%, p=0.034). Hematologic toxicities of grade 3 or 4 were more common in sunitinib group (4.2% vs 44.6%, p<0.001), and also was grade 3 or 4 hypertension, although it was not statistically significant (4.2% vs 13.7%, p=0.06). Age (> 60 years), duration from diagnosis to treatment (less than 1 year), Anemia, Neutrophilia, thorombocytosis, bone and liver metastases were independent prognostic factors affecting OS. Multivariate analysis also showed first-line VEGF TKI did not affect OS [hazard ratio (HR, sorafenib vs sunitinib) = 0.94, p=0.774]. Conclusions: Sorafenib showed comparable efficacy to sunitinb and demonstrated superiority in toxicities in the treatment of mRCC patients.
Sunitinib dosing, toxicity, and outcomes in first-line advanced renal cell carcinoma (aRCC): A U.S. Oncology Network (USON) retrospective study.
Authors: Schnadig Ian D. , Hutson Thomas E. , Chung Hsingwen , Dhanda Rahul , Halm Melissa , Forsyth Michael T. , Vogelzang Nicholas J. 
Published: March 2020

e15089 Background: Sunitinib is a first-line therapy for patients (pts) with aRCC. As a multitargeted tyrosine kinase inhibitor (TKI), it is associated with toxicities that may impact dosing; dose reductions may result in inferior clinical outcomes (Motzer, 2011 ASCO GU, abstract LBA308). This retrospective study was initiated by USON to evaluate dosing patterns of first-line sunitinib, and its association with toxicities and outcomes in community practices. Methods: Pts with aRCC who started first-line sunitinib between June 1, 2007 and May 31, 2011 at 17 USON practices were identified; clinical data were extracted by chart review from iKnowMed electronic medical records that were linked to USON retail pharmacy database. Pts who were enrolled in clinical trials or receiving care for other primary tumors were excluded. Results: Pt characteristics: N=134; median age = 64 years (range 41–87); ECOG PS 0/1 = 85%; clear cell RCC = 81%; and nephrectomy = 61%. Objective response rate was 16%. Overall survival (OS) was 15.4 months (95% confidence interval 11.9–20.8). Median treatment duration was 4 cycles (range 1–19): 27 pts (20.1%) received only 1 cycle of sunitinib (23 at full dose [50 mg] and 4 at <full dose); 107 pts (79.9%) received >1 cycle of sunitinib (53 received full dose; 35 started at full dose but were dose-reduced; 14 always received <full dose; 5 started at <full dose but were dose-increased to 50 mg). Overall, 45 pts were dose-reduced, principally (93%) due to toxicities; 67% of all dose reductions occurred in the first 3 cycles. 121 pts discontinued sunitinib after completing at least 1 cycle, mostly due to disease progression (PD; 44%) or toxicities (17%); 74% of all discontinuations occurred within the first 5 cycles. Conclusions: RCC pts in community practices commonly undergo sunitinib dose reductions in the first 3 cycles due to toxicities, and discontinue therapy within the first 5 cycles due to PD. The median number of cycles and OS were lower than those reported in clinical trials (Motzer JCO 2009;27:3584–3590). More selective TKIs are needed to reduce toxicities, optimize dosing, and potentially improve outcomes. Funded by a grant from AVEO Pharmaceuticals, Inc.
Safety and efficacy of pazopanib in heavily pretreated and treatment-naive patients with metastatic renal cell carcinoma (mRCC): A single center experience of the Medical University of Vienna, Austria.
Authors: Schmidinger Manuela , Bojic Marija , Vogl Ursula Maria , Klingler Christoph , Kramer Gero , Zielinski Christoph 
Published: March 2020

e15090 Background: Treatment with pazopanib was shown to improve objective response rates (ORR) and progression free survival (PFS) when compared to placebo in treatment-naïve or cytokine-pretreated patients with mRCC. We assessed the efficacy and safety of pazopanib in an unselected group of mRCC-patients at the Medical University of Vienna. Methods: Medical records of all patients who were treated with pazopanib between June 2010 and January 2012 were retrospectively reviewed. Pazopanib was prescribed at a dose of 800 mg daily. Treatment was given until disease progression or unacceptable toxicity. ORR was assessed by RECIST criteria. PFS and overall survival (OS) were calculated from the first day of pazopanib until progression and/or death, respectively. Results: Forty patients with a median age of 69 years (range 47-82) are currently evaluable for this analysis. The majority of patients (61%) presented with an ECOG Performance status of 0 and were classified as intermediate risk (55%) according to the MSKCC risk group classification. All patients had undergone nephrectomy and the majority (75%) had predominantly clear cell tumors. Most of the patients (66%) were diagnosed with three or more metastatic sites. Eighty percent of the patients were heavily pretreated, most commonly with three or more different types of targeted agents. Eight patients (20%) received pazopanib in first-line. Objective remission and disease stabilization were observed in 27% and 30% of the entire population. PFS and OS were 5 months (95%CI 3.07-6.86) and not reached, respectively. The most commonly observed all grade toxicities included fatigue (97%), anorexia (78%), hypertension (82%), diarrhoea (73%), nausea (62%) and vomiting (54%). The most common grade 3 or 4 toxicities were fatigue (68%), hypertension (47%) and diarrhoea (29%). Conclusions: Pazopanib appears effective in the setting of extensively pretreated patients. A later stage of the disease might have led to the unexpected higher incidence of off-target side effects such as fatigue and gastro-intestinal symptoms.
VEGF-VEGFR pathway and its activitation in renal cell carcinoma: Role in sunitinib response.
Authors: Rubio Gustavo , Casado Victoria , Leon Ana , Domine Manuel , Zazo Sandra , Lobo Francisco , Izarzugaza Yann , Arranz Juan Luis , Martin-Valades Jose Ignacio , Serrano Gloria , Carames Cristina , Madoz Juan , Rincon Raul , Canadas Carmen , Perez-Gonzalez Nuria , Fernandez-Acenero Maria Jesus , Cordova Sharon , Campos Angel , Rojo Federico , Garcia-Foncillas Jesus 
Published: March 2020

e15094 Background: Activation of VEGFR through its phosphorylation at specific tyrosine residues promotes changes in the microvasculature density. Inhibition of this mechanism targeting kinase activity has demonstrated an impact on clinical benefit in renal cell carcinoma. Methods: Fifty renal cell carcinomas have been assessed to evaluate the role of VEGF-VEGFR pathway and its impact on microvascular density (MVD). In order to identify parameters of potential clinical benefit to sunitinib a control group was included. IHC of VEGF, VEGFR (KDR), phosphorylated VEGFR-Y1175 and microvascular density assessment were performed. Results: All cases show VEGF expression; using a ROC curve a threshold was identified with a statistical significant worse PFS in those cases with higher VEGF expression in the whole series of patients treated with sunitinib (p=0.037) and in the subgroup with clear cell histology only (p=0.011). pKDR was positive in 40%: with an AUC=0.9 and according to this threshold statistical significance was found in PFS in the whole series (p=0.016) and in the clear cell subgroup (p=0.007). Microvascular density showed a statistical significance when was evaluated in terms of PFS in the group including all histologies (p=0.011) and those cases with clear cell subtype only (p=0.005). Conclusions: Our data suggest that VEGF, pKDR-Y1175 and MVD may identify the patients with significant clinical benefit to sunitinib in terms of statistically longer PFS.
Characterization of prostate cancer information available on smartphones.
Authors: Landau Danny , Hajdenberg Julio 
Published: March 2020

e15102 Background: When seeking information regarding prostate cancer, patients are often turning to Smartphones. We decided to look at the “top applications” (apps) on the iTunes store to determine the quality of information provided. Methods: In November 2011 on an iPhone the search “Prostate Cancer” was entered. The first page of apps was downloaded and studied (18 in total). They were categorized into apps written at a provider level and apps written for a patient level. The patient apps were then broken into patient support, cancer detection, disease monitoring, advertisements, and patient knowledge. The quality of paid apps was also looked at. Results: Of the 18 apps, two were unrelated to prostate cancer. Of the remaining 16, six were provider apps. Of these six, two were apps for major oncology journals, three were staging guidelines, and one was for a general oncology reference guide. Of the patient directed apps, patient information (general prostate cancer information) apps were four, two were apps to provide support, one was devoted to disease detection which included discussions on prostate specific antigen testing, one for monitoring disease, and one was an advertisement for a radiation technique. One app, once downloaded, required additional payment and personal information prior to giving the promised information. This application was not pursued. Paid apps accounted for eight apps. Two were geared toward providers. Both were prostate cancer staging guidelines. The patient directed paid apps included two apps which provided medically appropriate, level one evidence based information. Two provided information that wasn’t based on accepted medical therapy, including diet advice to prevent cancer and “alternative therapies” including reflexology, roots, and hypnosis as therapies. All free apps that were devoted to prostate cancer were based on level one evidence. Two additional paid apps were unrelated to prostate cancer. Conclusions: The majority of applications available over the iTunes store provide solid evidence and may be a valuable resource to patients and providers. Only the patient directed paid apps provided information that can be deemed questionable.
Augmentation of the cytotoxicity of ibandronate by y-27632, a rho kinase inhibitor, in prostate cancer cells.
Authors: Ata Alper , Ozcimen Ata , Kurt Hakan , Tiftik Nalan , Arican Ali , Buyukafsar Kansu 
Published: March 2020

e15104 Background: Bisphosphonates, which have been used for the treatment of breast and prostate cancers (Epplen et al., 2011) inhibit mevalonate pathway that results in the reduction of Ras prenylation, which eventually inhibits tumor growth (Luckman et al., 1998). Rho/Rho kinase signaling has a fundamental role in cancer cell proliferation, migration and metastasis (Vega et al., 2008) Therefore, in this study, we aimed to investigate effects of Y-27632, which inhibits Rho-kinase, ibandronate, which inhibits farnesyl transferase and their combination on cell proliferation in prostate cell lines, PC-3. Methods: The adherent prostate cell line, PC-3 (ATCC) was grown in RPMI-1640 supplemented with 10 % fetal bovine serum, 1 % L-glutamine, 1 % penicillin (10.000U/ml) and streptomycin (10.000 mg/ml) in a humidified atmosphere of 5 % CO2 at 37oC for confluency. The cells were seeded in the wells of E-plates (24,000 cells/well) that allowed a real-time-monitoring of the cell index reflected cell growth and proliferation (xCELLigence, Roche). The cell index was evaluated at the different points of time (post-treatment 12, 24, 36, 48, 60 and 72 h) in the groups of ibandronate, Y-27632, the combination and time-course control. Results: Ibandronate (10-100 mM), Y-27632 (50-100 mM) markedly decreased cell index. The combination of Y-27632 with ibandronate resulted in potentiation of cytotoxicity in PC-3 cells. Conclusions: Rho kinase inhibitors, biphosphonates and their combination may be beneficial for the treatment of prostate cell cancers.
Heterogeneity of treatment effects (HTE) in stage IV prostate cancer (S4PC).
Authors: Mitikiri Nirupama Devi , Reese Emily S , Hussain Arif , Onukwugha Ebere , Mullins C. Daniel ,   University of Maryland
Published: March 2020

e15108 Background: HTE occurs when patient factors modify a treatment’s effect on health outcomes so patients in the same study have different responses to a specific treatment. Variation in outcomes is caused by interactions between the factors causing HTE and the treatment. HTE may explain some of the heterogeneity in S4PC prognosis. The HTE literature is evolving; hence some factors causing HTE in S4PC are not yet documented. Methods: A systematic literature review (1946-2011) of published trials and observational studies identified evidence of statistically significant factors influencing HTE in S4PC. Inclusion criteria required that articles examine the impact of HTE factors on survival (OS, DSS, PFS) or health-related quality-of-life measures among S4PC patients. Factors that influenced outcomes but were not specifically evaluated in the context of HTE were excluded. Results: Of 398 articles that included key words, 33 met inclusion/exclusion criteria. Treatments included chemotherapy, radiation, hormonal therapy and bone-modifying agents. Both biologic and non-biologic factors (Table) were found to be associated with HTE in S4PC. Evidence was mixed regarding whether HTE in S4PC is influenced by race or by confounding factors correlated with race or both. As no articles examined prognostic factors such as bcl2, PTEN, p53, Pgp and EGFR status in the context of a specific treatment, such factors were excluded. Conclusions: Current evidence reveals diverse factors influencing HTE in S4PC.Ultimately, such knowledge can help oncologists prescribe more personalized medicine, help patients make more informed treatment choices, and aid policy making and treatment coverage decisions. [Table: see text]
The impact of image-guided radiotherapy (IGRT) for prostate cancer (PC) on radiotherapy (RT)-related acute toxicities and prostate-specific antigen (PSA) kinetics.
Authors: Poon Darren M. C. , Leung CM , Chu CM , Lee WY , Lee Louis , Kam Michael K. , Leung Sing Fai , Yu Kwok Hung , Chan Anthony T. C. 
Published: March 2020

e15110 Background: IGRT for PC could potentially improve the therapeutic ratio by enhancing accuracy of delivery of radiation to the prostate gland. Our aim is to compare the treatment outcomes in terms of RT-related acute toxicities and PSA kinetics of PC patients (pts) undergoing radical intensity-modulated radiotherapy (IMRT) with or without image-guidance. Methods: A cohort of 21 consecutive pts treated by IGRT (I) from January 2010, when the IGRT system was introduced in our institution, was compared with an immediately precedent cohort of 21 pts receiving IMRT without image-guidance (Non-I). The prescription dose (76Gy in 38 fractions) and the treatment margins were the same between the 2 groups (gps). In the I gp, daily online verification and correction of treatment position was performed with reference to image registration of the daily pre-treatment on-board imaging with the corresponding digitally reconstructed radiographs, based on three-dimensional matching of three intra-prostatic fiducial markers. Androgen deprivation therapy was not used in both gps. Acute toxicities were scored weekly during the course of RT according to the Common Terminology Criteria for Adverse Events Version 4.02. The pre- and the post-RT PSA within 6 months after completion of RT were obtained. The PSA halving time (PSAHT) was calculated by first order kinetics. Results: There was no statistically significant difference regarding the baseline clinical characteristics (age, PSA at diagnosis, Gleason score, T staging) between the gps. No grade 3 or 4 acute genitourinary (GU) or gastrointestinal (GI) toxicities was encountered in either gps. Acute grade 1 or 2 GI toxicities were significantly less frequent in the I gp (23.8% vs 81.0%, p=0.001), and their median duration of such toxicity were also significantly shorter (0.33 week vs 1.38 week, p=0.004).The frequencies of acute grade 1 or 2 GU toxicities were comparable between both gps (66.6% vs 81.0%, p=0.45).The I gp had a shorter median PSAHT than the non-I gp (3.36 week vs 5.49 week, p=0.09). Conclusions: IGRT is effective in reducing acute GI toxicities in treatment of PC, and may have more favorable PSA kinetics.
A cohort compassionate-use program with cabazitaxel plus prednisone for patients with metastatic castration-resistant prostate cancer: Interim results.
Authors: Bavbek Sevil E. , Malik Zafar I , Di Lorenzo Giuseppe , Scholz Hans-Jorg , van Oort Inge M , Ng Siobhan , Ozguroglu Mustafa , Gerritsen Winald R. , Mueller Stefan , Marttila Timo , Antón Aparicio Luis M. , Albers Peter , Gschwend Jürgen E. , Bensfia Samira , Ecstein-Fraïssé Evelyne B , Bracarda Sergio , Heidenreich Axel 
Published: March 2020

e15112 Background: In the TROPIC trial (NCT00417079), treatment with CbzP produced a statistically significant improvement in overall survival vs mitoxantrone + prednisone (MP) in patients (pts) with mCRPC previously treated with a docetaxel (D)-containing regimen (HR 0.70; p< 0.0001). These results supported the establishment of 2 programs (based on local regulations): a compassionate use (CUP) and an early access program (EAP; NCT01254279). Methods: The aims of the CUP/EAP are to provide drug to pts with mCRPC who may benefit from CbzP prior to commercial availability and further assess CbzP safety profile. Total enrollment for both programs is estimated at 1600 pts from 250 centers globally. Eligible pts receive CbzP (25 mg/m2 Q3W + prednisone 10 mg PO QD) until disease progression, death, unacceptable toxicity or physician/pt decision. Results: Baseline characteristics and safety data are available for the first 399 pts: median age was 68 yrs (range 43–89), with 90.2% ECOG PS 0–1. The median cumulative dose of prior D was 675 mg/m2; prior therapy with MP was permitted. For pts whose disease progressed following D, median time from last dose of D to progression was 4 months; 53.3% of pts experienced disease progression either during or < 3 months after D. 61% of pts had ≥ 2 metastatic sites; the most common were bone (93.2%) and regional lymph nodes (34.4%). At the time of analysis, a median of 4 cycles of CbzP had been administered; 4 pts received ≥ 10 cycles. Median relative dose intensity was 99.2% (range 80.1–104.9). G-CSF was administered to 34.3% of pts in Cycle 1 (6.3% therapeutic, 26.6% prophylactic). Overall, 71.4% of pts had adverse events (AEs; all grades). Most common grade 3-4 AEs were neutropenia 11.3%, febrile neutropenia 6.3%, anemia 2.8%, fatigue 2%, neutropenic sepsis 1.8%, vomiting 1.3% and diarrhea 1%. Eight (2%) treatment-related deaths were reported. Conclusions: The CUP/EAP provides additional safety data for CbzP in a routine clinical practice pt population with heavily pre-treated mCRPC. Treatment with CbzP was tolerable, with a predictable and manageable toxicity profile consistent with data reported for TROPIC and the product labeling.