Publications by authors named "Elizabeth R Kessler"

30 Publications

  • Page 1 of 1

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

N Engl J Med 2021 03;384(9):829-841

From the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London (T.P.); the Bradford Hill Clinical Research Center, Santiago, Chile (M.B.); the Department of Medical Oncology, Gustave Roussy, Villejuif, France (B.E.); the Department of Hemato-Oncology, Urologic Oncology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City (M.T.B.), the Department of Medical Oncology, Centro Universitario contra el Cáncer, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Nuevo León (V.M.O.J.), and the Department of Medical Oncology, Hospital H+ Querétaro, Querétaro (J.P.F.) - all in Mexico; the Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz (B.Z.), and the Department of Clinical Oncology and Hematology, Regional Specialist Hospital, Biała Podlaska (J. Żołnierek) - both in Poland; the Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis (J.J.H.); Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua (U.B.), the Department of Medical Oncology, Ospedale San Donato, Istituto Toscano i, Arezzo (A.H.), the Department of Internal Medicine, University of Pavia, Pavia (C.P.), and the University of Bari "A. Moro," Bari (C.P.) - all in Italy; the Department of Genitourinary Medical Oncology, M.D. Anderson Cancer Center, Houston (A.Y.S.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C.S.); the Department of Medical Oncology, Royal Brisbane and Women's Hospital, Herston, QLD (J.C.G.), and Cabrini Monash University Department of Medical Oncology, Cabrini Health, Malvern, VIC (D.P.) - both in Australia; the Oncology Research Center, Hospital São Lucas, Porto Alegre, Brazil (C.B.); Fundacion Richardet Longo, Instituto Oncologico de Cordoba, Cordoba (M.R.), and Instituto Multidisciplinario de Oncología, Clínica Viedma, Viedma (R.K.) - both in Argentina; the Division of Medical Oncology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora (E.R.K.); the Departments of Urology and Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Y.T.), and the Department of Urology, Keio University School of Medicine, Tokyo (R.M.) - both in Japan; the Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany (J.B.); the Departments of Clinical Research (J. Zhang.), Clinical Oncology (M.A.M.), Biostatistics (B.S.), and Health Economics and Outcomes Research (F.E.), Bristol Myers Squibb, Princeton, NJ; the Department of Clinical Oncology, Exelixis, Alameda, CA (G.M.S.); the Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (A.B.A.); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).

Background: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.

Methods: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point.

Results: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib.

Conclusions: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2026982DOI Listing
March 2021

Feasibility and Acceptability of a Remotely Delivered, Web-Based Behavioral Intervention for Men With Prostate Cancer: Four-Arm Randomized Controlled Pilot Trial.

J Med Internet Res 2020 12 31;22(12):e19238. Epub 2020 Dec 31.

Oregon Health and Science University, Portland, OR, United States.

Background: Diet and exercise may be associated with quality of life and survival in men with prostate cancer.

Objective: This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer.

Methods: We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls-one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes.

Results: In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1.

Conclusions: A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations.

Trial Registration: ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/19238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808895PMC
December 2020

Web-Based Lifestyle Interventions for Prostate Cancer Survivors: Qualitative Study.

JMIR Cancer 2020 Nov 10;6(2):e19362. Epub 2020 Nov 10.

University of California, San Francisco, San Francisco, CA, United States.

Background: Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population.

Objective: This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits.

Methods: TrueNTH's Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods.

Results: In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors' long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention.

Conclusions: These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants' technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory-based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/19362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685923PMC
November 2020

Prostate Cancer Central Nervous System Metastasis in a Contemporary Cohort.

Clin Genitourin Cancer 2020 Aug 22. Epub 2020 Aug 22.

Division of Medical Oncology, University of Colorado, School of Medicine, Aurora, CO. Electronic address:

Introduction: Central nervous system (CNS) metastasis from prostate cancer (PCA) is a rare event, but one with significant prognostic impact for those affected. There are limited data on its impact in contemporary cohorts treated with modern agents.

Patients And Methods: A retrospective institutional review was performed to characterize the occurrence/outcome of PCA CNS metastasis on all cases of PCA from 2011 to 2017. A manual chart review was performed to confirm PCA CNS metastases in all cases identified through a diagnostic code screening of the health data.

Results: A total of 6596 cases of PCA were identified, with 29 (20 dural and 9 intraparenchymal) confirmed cases of CNS metastases from PCA. The median survival from the time of diagnosis of CNS metastasis was 2.6 months (95% confidence interval, 2.04-10.78 months) and 5.41 months (95% confidence interval, 3.03 months to not reached) for dural and parenchymal metastases, respectively. Among those who developed CNS metastases, approximately 79% of patients had prior exposure to abiraterone and/or enzalutamide, of whom 50% had ≥ 6 months of exposure. Four (0.07%) of the 5841 patients developed CNS metastases prior to the initiation of therapy or on androgen deprivation therapy alone. In contrast, 24 (8.6%) of the 279 patients with 2 or more lines of medical therapy developed CNS metastases.

Conclusions: Our analysis highlights the continued poor prognosis of parenchymal and dural CNS metastases from PCA. CNS metastases in PCA remain a rare event with a 0.4% incidence in this series, but this incidence is considerably increased in patients who receive medical therapy beyond first-line androgen deprivation therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clgc.2020.07.012DOI Listing
August 2020

Treating Elderly Patients With Muscle-Invasive Bladder Cancer.

J Natl Compr Canc Netw 2020 06;18(6):783-790

2University of Colorado Cancer Center; and.

Bladder cancer is an extremely common cancer that primarily affects individuals aged >65 years. In caring for patients with bladder cancer, clinicians must also consider care of older persons in general. Management of muscle-invasive bladder cancer (MIBC) involves multidisciplinary treatment planning, because curative-intent therapy includes either surgery or radiation, with consideration of the role of systemic therapy. As clinicians develop a treatment plan, considering a geriatric oncology perspective may enhance patient care and influence outcomes for this large and growing population. Similarly, treatment plan development must also consider aspects unique to an older patient population, such as altered organ function, increased comorbidity, decreased functional reserve, and perhaps altered goals of treatment. Thus a thorough evaluation inclusive of disease assessment and geriatric assessment is essential to care planning. Population-based data show that as patients with MIBC age, use of standard therapies declines. Given the complexities of coordinating a multidisciplinary care plan, as well the complexities of treating a heterogeneous and potentially vulnerable older patient population, clinicians may benefit from upfront assessments to inform and guide the process. This review highlights the unique treatment planning considerations for elderly patients diagnosed with MIBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2020.7585DOI Listing
June 2020

Identifying Geriatric Oncology Competencies for Medical Oncology Trainees: A Modified Delphi Consensus Study.

Oncologist 2020 07 1;25(7):591-597. Epub 2020 Apr 1.

City of Hope National Medical Center, Duarte, California, USA.

Background: Most oncology trainees are not taught about the needs of older patients, who make up the majority of patients with cancer. Training of health care providers is critical to improve the care of older adults with cancer. There is no consensus about which geriatric oncology (GO) competencies are important for medical oncology trainees. Our objective was to identify GO competencies medical oncology trainees should acquire during training.

Materials And Methods: A modified Delphi consensus of experts in oncology medical education and GO was conducted. Experts categorized at what training stage proposed competencies should be attained: internal medicine, oncology, or GO training. Consensus was obtained if two thirds of experts agreed on the training stage at which the competency should be attained.

Results: A total of 78 potential competencies were identified, of which 35 (44.9%) proposed competencies were felt to be appropriate to be acquired during oncology training. The majority of the identified competencies pertained to prescribing of systemic therapy (n = 12) and psychosocial and supportive care (n = 13). No competencies related to geriatric assessment were identified for acquisition during oncology training.

Conclusion: Experts in oncology education and geriatric oncology agreed upon a set of GO competencies appropriate for oncology trainees. These results provide the foundation for developing a GO curriculum for medical oncology trainees and will hopefully lead to better care of older adults with cancer.

Implications For Practice: The aging population will drive the projected rise in cancer incidence. Although aging patients make up the majority of patients diagnosed with cancer, oncologists rarely receive training on how to care for them. Training of health care providers is critical to improving the care of older adults with cancer. The results of this study will help form the foundation of developing a geriatric oncology curriculum for medical oncology trainees.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1634/theoncologist.2019-0950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356779PMC
July 2020

Reply by Authors.

J Urol 2020 04 22;203(4):697-698. Epub 2020 Jan 22.

Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000000644.02DOI Listing
April 2020

Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery in Patients with High Grade Upper Tract Urothelial Carcinoma.

J Urol 2020 04 8;203(4):690-698. Epub 2019 Nov 8.

Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: Data supporting neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma are scant. In this multi-institution, prospective, phase II trial we investigated pathological complete responses after neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma.

Materials And Methods: Patients with high grade upper tract urothelial carcinoma in whom nephroureterectomy was planned were assigned to 4 neoadjuvant chemotherapy cycles of accelerated methotrexate, vinblastine, doxorubicin and cisplatin in those with baseline creatinine clearance greater than 50 ml per minute or gemcitabine and carboplatin in those with creatinine clearance 30 to 50 ml per minute or less. The study primary end point was a pathological complete response (ypT0N0). The accrual goal was 30 patients per arm. An 18% pathological complete response was considered worth further study while a 4% pathological complete response would not have justified pursuing this regimen. With 28 eligible patients per arm success was defined as 3 or more pathological complete responses (10.7%) in a given arm. Secondary end points included safety, renal function and oncologic outcomes.

Results: A total of 30 patients enrolled in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm from 2015 to 2017. Six patients enrolled in the gemcitabine and carboplatin arm, which closed due to poor accrual. Of the 29 patients eligible for accelerated methotrexate, vinblastine, doxorubicin and cisplatin, including 23 men and 6 women with a median age of 65 years (range 40 to 84), 80% completed all planned treatments, 3 (10.3%) achieved ypT0N0 and 1 achieved ypT0Nx for a pathological complete response in 13.8% (90% CI 4.9-28.8). In 1 patient receiving accelerated methotrexate, vinblastine, doxorubicin and cisplatin nephroureterectomy was deferred due to grade 4 sepsis. The grade 3-4 toxicity rate was 23% in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm with no grade 5 event.

Conclusions: Accelerated methotrexate, vinblastine, doxorubicin and cisplatin neoadjuvant chemotherapy in patients with high grade upper tract urothelial carcinoma and creatinine clearance greater than 50 ml per minute was safe and demonstrated predefined activity with a 14% pathological complete response rate. Final pathological stage ypT1 or less in more than 60% of patients is encouraging. Together the results of this prospective trial support the use of neoadjuvant chemotherapy in eligible patients with high grade upper tract urothelial carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000000644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735436PMC
April 2020

Time from definitive therapy to onset of metastatic disease predicts outcomes in men with metastatic hormone sensitive prostate cancer.

Urol Oncol 2019 06 13;37(6):352.e19-352.e24. Epub 2019 Feb 13.

Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT. Electronic address:

Purpose: Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities. Not all men with mHSPC may be candidates for these intensified regimens, yet there are no clinical models or biomarkers used to optimize treatment selection. Herein, we hypothesized that longer time from prior definitive therapy (DT), either radical prostatectomy, definitive radiotherapy, or both, to onset of metastatic disease is associated with improved survival outcomes in men with newly diagnosed mHSPC.

Methods: This multicenter retrospective study included men initiating systemic therapy with ADT for new mHSPC. Kaplan-Meier and COX proportional hazard models assessed time to metastatic castration-resistant prostate cancer (mCRPC) and overall survival (OS) by receipt of prior DT.

Results: Of the 253 men with new mHSPC, 115 (45%) had received prior DT. In a multivariate analysis, increasing years from DT to the start of ADT was an independent predictor of time to mCRPC (per year: hazard ratio 0.91 95% confidence interval 0.84-0.99, P = 0.020) and improved OS (per year: hazard ratio 0.87, 95% confidence interval 0.74-0.99, P = 0.0025) in patients with new mHSPC, and may assist with risk stratification in these patients at time of mHSPC.

Conclusion: Time from DT to start of ADT is an independent predictor of time to mCRPC and OS in men with new mHSPC, and may assist with risk stratification of these patients for systemic therapy selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urolonc.2019.01.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857455PMC
June 2019

Adult Wilms Tumor During Pregnancy: Case Report and Literature Review.

Urology 2019 Jul 28;129:200-205. Epub 2018 Dec 28.

University of Colorado, Department of Surgery, Division of Urology, Aurora, CO. Electronic address:

Adult Wilms tumor (WT) is a well-known, albeit rare entity and has historically been associated with worse overall clinical outcomes when compared to younger patients. Because WT is uncommon in adult patients, it is often misdiagnosed and treated off standardized pediatric protocols. WT associated with pregnancy is even more rare, and there is not a standardized approach to this small subset of patients. We present a case of an adult WT discovered and managed during the perinatal period and review prior published cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2018.11.045DOI Listing
July 2019

Management of Metastatic Prostate Cancer in Frail/Elderly Patients.

Oncology (Williston Park) 2018 11;32(11):570-3

As the world population ages, we can expect to care for an increasing number of older cancer patients. Prostate cancer is inherently a condition that affects patients of advanced age. In caring for these patients who have advanced prostate cancer, it is important to first assess the health status of the patient and his goals of care. As this is established, likely through a geriatric assessment, this will inform how to modify or mold the treatment plan to fit a patient's needs and vulnerabilities. These vulnerabilities may surface as patients undergo treatment such as androgen deprivation therapy-the backbone of systemic therapy for advanced disease. Androgen deprivation therapy leads to long-term adverse effects; therefore, providers should carefully consider its use and proactively manage toxicity. It is important to assess patients before starting treatment and to adjust the choice of therapy, or supportive services, in order to maximize benefit and minimize potential harms.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2018

Effect of Increasing Levels of Web-Based Behavioral Support on Changes in Physical Activity, Diet, and Symptoms in Men With Prostate Cancer: Protocol for a Randomized Controlled Trial.

JMIR Res Protoc 2018 Nov 15;7(11):e11257. Epub 2018 Nov 15.

Department of Urology, University of California, San Francisco, San Francisco, CA, United States.

Background: More than 3.1 million men in the United States are prostate cancer survivors. These men may improve their physical function, quality of life, and potentially their prognosis by adopting healthier lifestyle habits. The internet provides a scalable mechanism to deliver advice and support about improving physical activity and dietary habits, but the feasibility and acceptability of a Web-based lifestyle intervention and the dose of support necessary to improve health behaviors are not yet known.

Objectives: The Community of Wellness is a Web-based intervention focused on supporting exercise and healthy dietary practices for men with prostate cancer. The objectives of this study were to determine the feasibility, acceptability, and preliminary efficacy of the Community of Wellness Web portal among prostate cancer survivors by conducting a randomized controlled trial (RCT) comparing 4 levels of additive Web-based content and interaction with participants: Level 1 (Teaching; Control), Level 2 (Teaching + Tailoring), Level 3 (Teaching + Tailoring + Technology), and Level 4 (Teaching + Tailoring + Technology + Touch).

Methods: This is a single-blinded RCT comparing 3 levels of behavioral support within the Community of Wellness Web portal intervention (Levels 2 to 4) with each other and with the control condition (Level 1). The control condition receives general static Web-based educational information only on physical activity and dietary habits, self-efficacy for behavior change, motivation for physical activity, and changes in anxiety and treatment-related side effects. We will enroll and randomize 200 men with prostate cancer equally to 4 levels of the Community of Wellness Web-based intervention for 3 months (50 men per level). Surveys will be completed by self-report at baseline, 3 months (immediately postintervention), and 6 months (3 months postintervention). Feasibility and acceptability will be assessed by enrollment statistics, Web-based usage metrics, and surveys at the 3-month time point. We will also conduct focus groups after the postintervention follow-up assessment in a sample of enrolled participants to evaluate elements of usability and acceptability that cannot be obtained via surveys.

Results: Enrollment is ongoing, with 124 enrolled. Study completion (6-month follow-up) is expected by July 2019.

Conclusions: The goal of the study is to identify the level of support that is feasible, acceptable, promotes behavior change, and improves health in men with prostate cancer to inform future efforts to scale the program for broader reach.

Trial Registration: ClinicalTrials.gov NCT03406013; https://clinicaltrials.gov/ct2/show/NCT03406013 (Archived by WebCite at http://www.webcitation.org/73YpDIoTX).

International Registered Report Identifier (irrid): PRR1-10.2196/11257.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/11257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265599PMC
November 2018

Phase II Trial of Acai Juice Product in Biochemically Recurrent Prostate Cancer.

Integr Cancer Ther 2018 12 5;17(4):1103-1108. Epub 2018 Oct 5.

1 University of Colorado, Aurora, CO, USA.

Background: Plant derivatives have been studied as therapies for prostate cancer based on their purported anti-inflammatory and antioxidant properties and low toxicities. The acai berry is an example of a plant rich in phytochemicals, which may slow the growth of prostate cancer.

Methods: This was a phase II, Simon 2-stage clinical trial in patients with biochemically recurrent prostate cancer with a primary endpoint of prostate-specific antigen (PSA) response. Patients were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with twice daily intake of Acai Juice Product until PSA progression, with a primary endpoint of PSA response.

Results: Twenty-one patients were enrolled in the first stage of the trial. One of those patients had a PSA response within the study time period. The PSA doubling time was lengthened in 71% of patients (95% confidence interval = 48% to 89%) on the trial, and in a small number of responders, this was sustained over an extended time.

Conclusions: This study did not meet its primary endpoint of 50% PSA response. Nevertheless, the overall tolerability and effects on PSA stabilization warrant further exploration in a biochemically recurrent population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1534735418803755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247557PMC
December 2018

Treatment of Urothelial Cancer in Elderly Patients: Focus on Immune Checkpoint Inhibitors.

Drugs Aging 2018 05;35(5):409-421

University of Colorado School of Medicine, Denver, CO, USA.

Urothelial carcinoma, or bladder cancer, is a malignancy that most commonly affects older patients. The median age at diagnosis is 73 years, and care of these patients requires consideration not just of the disease-related factors such as stage and histology, but also of patient-related factors. Many of these patients have concurrent medical morbidities and additional changes related to the aging process. Older patients with cancer are a unique population requiring additional considerations and assessment in treatment decision-making. It is important to look beyond chronologic age. The traditional treatment for advanced disease has relied on platinum-based chemotherapy. These multi-agent regimens require consideration of baseline organ function as well as competing conditions that may heighten toxicity. The advent of a new class of cancer therapeutics, the immune checkpoint inhibitors, has changed the care of patients with advanced disease considerably. These immunotherapeutics have been approved for treating patients with disease progression on chemotherapy, or those who are ineligible (or unfit) to receive cisplatin-based therapy. This expansion of the population of patients eligible for treatment has great applicability to the unique considerations in an older patient population. In general, these new immunotherapies are well tolerated and effective in this group of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40266-018-0540-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226359PMC
May 2018

Feasibility and Acceptability of a Best Supportive Care Checklist among Clinicians.

J Palliat Med 2018 08 23;21(8):1074-1077. Epub 2018 Apr 23.

6 Duke University School of Medicine, Duke Cancer Institute , Durham, North Carolina.

Context: Best supportive care (BSC) is often not standardized across sites, consistent with best evidence, or sufficiently described. We developed a consensus-based checklist to document BSC delivery, including symptom management, decision making, and care planning. We hypothesized that BSC can be feasibly documented with this checklist consistent with consolidated standards of reporting trials.

Objective: To determine feasibility/acceptability of a BSC checklist among clinicians.

Methods: To test feasibility of a BSC checklist in standard care, we enrolled a sample of clinicians treating patients with advanced cancer at four centers. Clinicians were asked to complete the checklist at eligible patient encounters. We surveyed enrollees regarding checklist use generating descriptive statistics and frequencies.

Results: We surveyed 15 clinicians and 9 advanced practice providers. Mean age was 41 (SD = 7.9). Mean years since fellowship for physicians was 7.2 (SD = 4.5). Represented specialties are medical oncology (n = 8), gynecologic oncology (n = 4), palliative care (n = 2), and other (n = 1). For "overall impact on your delivery of supportive/palliative care," 40% noted improved impact with using BSC. For "overall impact on your documentation of supportive/palliative care," 46% noted improvement. Impact on "frequency of comprehensive symptom assessment" was noted to be "increased" by 33% of providers. None noted decreased frequency or worsening impact on any measure with use of BSC. Regarding feasibility of integrating the checklist into workflow, 73% agreed/strongly agreed that checklists could be easily integrated, 73% saw value in integration, and 80% found it easy to use.

Conclusion: Clinicians viewed the BSC checklist favorably illustrating proof of concept, minor workflow impact, and potential of benefit to patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jpm.2017.0605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486661PMC
August 2018

Renal cell carcinoma: a review of biology and pathophysiology.

F1000Res 2018 12;7:307. Epub 2018 Mar 12.

Division of Medical Oncology, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO, USA.

Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/f1000research.13179.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850086PMC
March 2018

Patient characterization and usage trends of proton beam therapy for localized prostate cancer in the United States: A study of the National Cancer Database.

Urol Oncol 2017 06 15;35(6):438-446. Epub 2017 Feb 15.

Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO. Electronic address:

Purpose: To evaluate usage trends and identify factors associated with proton beam therapy (PBT) compared to alternative forms of external beam radiation therapy (RT) (EBRT) for localized prostate cancer.

Patients And Methods: The National Cancer Database was queried for men with localized (N0, M0) prostate cancer diagnosed between 2004 and 2013, treated with EBRT, with available data on EBRT modality (photon vs. PBT). Binary multiple logistic regression identified variables associated with EBRT modality.

Results: In total, 143,702 patients were evaluated with relatively few men receiving PBT (5,709 [4.0%]). Significant differences in patient and clinical characteristics were identified between those men treated with PBT compared to those treated with photon (odds ratio [OR]; 95% CI). Patients treated with PBT were generally younger (OR = 0.73; CI: 0.67-0.82), National Comprehensive Cancer Network low-risk compared to intermediate (0.71; 0.65-0.78) or high (0.44; 0.38-0.5) risk, white vs. black race (0.66; 0.58-0.77), with less comorbidity (Charlson-Deyo 0 vs. 2+; 0.70; 0.50-0.98), live in higher income counties (1.55; 1.36-1.78), and live in metropolitan areas compared to urban (0.21; 0.18-0.23) or rural (0.14; 0.10-0.19) areas. Most patients treated with PBT travelled more than 100 miles to the treatment facility. Annual PBT utilization significantly increased in both total number and percentage of EBRT over time (2.7%-5.6%; P<0.001). PBT utilization increased mostly in men classified as National Comprehensive Cancer Network low-risk (4%-10.2%).

Conclusion: PBT for men with localized prostate cancer significantly increased in the United States from 2004 to 2013. Significant demographic and prognostic differences between those men treated with photons and protons were identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urolonc.2017.01.013DOI Listing
June 2017

Patterns of care and survival outcomes for adolescent and young adult patients with testicular seminoma in the United States: A National Cancer Database analysis.

J Pediatr Urol 2017 Aug 17;13(4):386.e1-386.e7. Epub 2017 Jan 17.

Department of Surgery, Division of Urology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address:

Introduction: Testicular germ cell tumors (GCTs) are the most common solid tumor among adolescent and young adult (AYA) males. AYA patients with GCTs most typically have non-seminoma compared with seminoma, and accordingly there are fewer data reported on the AYA experience with testicular seminoma.

Objective: To evaluate national trends in postoperative treatment and overall survival (OS) outcomes in testicular seminoma by age group, specifically comparing AYAs with older adults.

Study Design: The National Cancer Data Base (NCDB) was queried for patients with testicular seminoma diagnosed between 2004 and 2012, who underwent orchiectomy followed by observation or adjuvant therapy (chemotherapy, radiation (RT), or both). Patients were grouped by age: AYA (15-39 years), adults between 40 and 55 years, and adults >55 years. Overall survival (OS) was presented using Kaplan-Meier curves and groups compared via a log-rank test. Univariate (UVA) and multivariate (MVA) analyses were performed using Cox proportional hazards regression models. Binary multiple logistic regression identified differences in variables by age category.

Results: Of the total 22,361 patients the majority were AYAs (12,880, 57.6%), followed by adults 40-55 years (8,022, 35.9%), and >55 years (1,459, 6.5%). Unadjusted 5-year OS was significantly better for AYAs versus adults 40-55 years and >55 years (98.0%, 96.4%, 87.7%; p < 0.001), as was 10-year OS (96.1%, 91.8%, 71.3% respectively; p < 0.001). The Table shows that on a MVA, OS was significantly better for AYAs versus adults 40-55 years and adults >55 years. AYA patients were also more commonly treated at centers with greater clinical volume. Additionally, AYA patients were less likely to present with metastatic disease. Accordingly, AYA patients were less likely to undergo retroperitoneal lymph node dissection (OR 0.81; p = 0.001) and were less often managed with adjuvant therapy including chemotherapy (OR 0.91; p = 0.027), RT (OR 0.93; p = 0.025), or both (OR 0.68; p = 0.020).

Discussion: AYA patients with testicular seminoma present with earlier stage disease and in the clinical Stage I setting are more often are managed with active surveillance following orchiectomy when compared with older adults in this population-based analysis. Among AYA patients, OS was modestly better when compared with adults 40-55 years and significantly better when compared with adults >55 years.

Conclusion: Our objective to describe the patterns of care and survival outcomes for AYA patients with testicular seminoma in the USA was met by reviewing this large national dataset. These results may inform future guidelines for management of AYA seminoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2016.12.009DOI Listing
August 2017

What is behind the flare phenomenon?

BJU Int 2016 12;118(6):845-846

Division of Medical Oncology, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bju.13554DOI Listing
December 2016

Survival outcomes of adolescent and adult patients with non-seminomatous testicular germ-cell tumors: A population-based study.

J Pediatr Urol 2016 Dec 6;12(6):405.e1-405.e9. Epub 2016 Aug 6.

Department of Surgery, Division of Urology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address:

Background: In adolescents, approximately 90% of testicular germ cell tumors (T-GCTs) are non-seminomas (NS T-GCTs). Few studies have evaluated the impact of age, specifically in adolescence, on outcomes of NS T-GCTs.

Objective: The purpose of this study was to review all patients diagnosed with NS T-GCTs in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the association between age (adolescents vs. adults) and survival outcomes.

Method: The SEER database was queried for individuals ≥13 years old diagnosed with NS T-GCTs from 1995 to 2012. Patients were categorized into adolescent (13-19 years) and adult (≥20 years) cohorts. A Cox proportional hazards model was used for multivariate analysis (MVA).

Results: A total of 13,963 patients (1496 adolescents, 12,467 adults) was included. Median follow-up was 71 months (range 1-215). Five-year overall survival (OS) for adolescent and adult patients was 94% and 92%, respectively (p = 0.007); 5-year cancer-specific survival (CSS) was 95% and 94%, respectively (p = 0.139). Under MVA, adolescent patients had improved OS (HR 0.61; 95% CI 0.50-0.75; p < 0.001) and CSS (HR 0.65; 95% CI 0.51-0.82; p < 0.001), when compared with adults (Table). In a logistic regression analysis adjusting for demographics, adolescent patients were more likely to present with regional or distant metastatic disease (OR 1.16; 95% CI 1.01-1.35; p = 0.039), undergo an orchiectomy (OR 2.44; 95% CI 1.50-4.00; p < 0.001) or tumor excision (OR 2.43; 95% CI 1.57-3.77; p < 0.001), and receive other adjuvant surgery (OR 5.87; 95% CI 2.25-15.30; p < 0.001).

Conclusions: To our knowledge, this is the largest population-based comparative analysis in NS T-GCTs comparing outcomes between these two age groups. Adolescent patients with NS T-GCTs had slightly improved survival compared with adults, despite presenting with more advanced disease. While adolescent patients present at more advanced stage, they achieve excellent survival outcomes possibly at the cost of a greater therapeutic burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2016.06.014DOI Listing
December 2016

Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers.

Invest New Drugs 2016 Apr 30;34(2):176-83. Epub 2015 Dec 30.

Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Room 8120, Aurora, CO, 80045, USA.

Background: Vandetanib is a multitargeted tyrosine kinase inhibitor that affects vascular endothelial growth factor receptor (VEGF), epidermal growth factor (EGF), and rearranged during transfection (RET) mediated receptors which are important for growth and invasion of biliary and pancreatic cancers. This phase I study evaluated the safety profile of vandetanib in combination with standard doses of gemcitabine and capecitabine in order to determine the maximum tolerated dose (MTD).

Methods: In this single center phase I trial, patients received gemcitabine intravenously (i.v.) at 1000 mg/m2 days 1, 8, 15 in a 28 day cycle, capecitabine orally at 850 mg/m2 twice daily on days 1-21, and escalating doses of vandetanib (200 or 300 mg orally daily). Once the MTD was defined, an expansion cohort of patients with advanced biliary cancers and locally advanced or metastatic pancreatic cancer was enrolled. Blood samples were also collected at predetermined time points for biomarker analysis.

Results: Twenty-three patients were enrolled: 9 in the dose escalation and 14 in the dose expansion cohort. One dose limiting toxicity (DLT), of grade 4 neutropenia, occurred in the 200 mg vandetanib cohort. The most common adverse effects were diarrhea (39 %), nausea and vomiting (34%), and rash (33%). There were 3 partial responses and stable disease of >2 months (range 2-45, median 5) was observed in 15/23 patients. There was no association between changes in biomarker analytes and disease response.

Conclusion: The combination of gemcitabine, capecitabine and vandetanib is well tolerated at the recommended phase II dose of gemcitabine 1000 mg/m2 weekly for three consecutive weeks, capecitabine 850 mg/m2 BID days 1-21, and vandetanib 300 mg daily, every 28 days. This combination demonstrated promising activity in pancreaticobiliary cancers and further evaluation is warranted in these diseases. NCT00551096.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-015-0316-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788525PMC
April 2016

Local control rates of metastatic renal cell carcinoma (RCC) to the bone using stereotactic body radiation therapy: Is RCC truly radioresistant?

Pract Radiat Oncol 2015 Nov-Dec;5(6):e589-e596. Epub 2015 Jun 30.

Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado.

Purpose: We report the radiographic and clinical response rate of stereotactic body radiation therapy (SBRT) compared with conventional fractionated external beam radiation therapy (CF-EBRT) for renal cell carcinoma (RCC) bone lesions treated at our institution.

Methods And Materials: Forty-six consecutive patients were included in the study, with 95 total lesions treated (50 SBRT, 45 CF-EBRT). We included patients who had histologic confirmation of primary RCC and radiographic evidence of metastatic bone lesions. The most common SBRT regimen used was 27 Gy in 3 fractions.

Results: Median follow-up was 10 months (range, 1-64 months). Median time to symptom control between SBRT and CF-EBRT were 2 (range, 0-6 weeks) and 4 weeks (range, 0-7 weeks), respectively. Symptom control rates with SBRT and CF-EBRT were significantly different (P = .020) with control rates at 10, 12, and 24 months of 74.9% versus 44.1%, 74.9% versus 39.9%, and 74.9% versus 35.7%, respectively. The median time to radiographic failure and unadjusted pain progression was 7 months in both groups. When controlling for gross tumor volume, dose per fraction, smoking, and the use of systemic therapy, biologically effective dose ≥80 Gy was significant for clinical response (hazard ratio [HR], 0.204; 95% confidence interval [CI], 0.043-0.963; P = .046) and radiographic (HR, 0.075; 95% CI, 0.013-0.430; P = .004). When controlling for gross tumor volume and total dose, biologically effective dose ≥80 Gy was again predictive of clinical local control (HR, 0.140; 95% CI, 0.025-0.787; P = .026). Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 toxicity reported.

Conclusions: SBRT is both safe and effective for treating RCC bone metastases, with rapid improvement in symptoms after treatment and more durable clinical and radiographic response rate. Future prospective trials are needed to further define efficacy and toxicity of treatment, especially in the setting of targeted agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prro.2015.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706456PMC
September 2016

What next? Choosing second-line therapy in progressive renal cell carcinoma.

Oncology (Williston Park) 2014 Sep;28(9):794-6

View Article and Find Full Text PDF

Download full-text PDF

Source
September 2014

Distress among caregivers of phase I trial participants: a cross-sectional study.

Support Care Cancer 2014 Dec 15;22(12):3331-40. Epub 2014 Aug 15.

Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17th Avenue, Aurora, CO, 80045, USA,

Purpose: The number of patients with cancer enrolling in phase I trials is expected to increase as these trials incorporate patient selection and exhibit greater efficacy in the era of targeted therapies. Despite the fact that people with advanced cancer often require a caregiver, little is known about the experience of caregivers of people enrolling in oncology phase I clinical trials. We conducted a cross-sectional study assessing the distress and emotion regulation of caregivers of phase I trial participants to inform the design of future interventions targeting the unique needs of this population.

Methods: Caregivers of oncology patients were approached at the patient's phase I clinical trial screening visit. Caregiver participants completed a one-time survey incorporating validated instruments to comprehensively assess distress and emotion regulation. Basic demographic information about both the caregiver and patient was collected.

Results: Caregivers exhibited greater distress than population norms. Emotion regulation was also moderately impaired. Respondents identified positive aspects of caregiving despite exhibiting moderate distress.

Conclusion: Enrollment of a patient in a phase I clinical trial is a time of stress for their caregivers. This pilot study demonstrates the feasibility of engaging caregivers of phase I trial participants and the need to better support them through this component of their caregiving experience.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-014-2380-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356007PMC
December 2014

Geriatric considerations in the treatment of advanced prostate cancer.

F1000Prime Rep 2014 6;6:33. Epub 2014 May 6.

University of Colorado Cancer Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045 USA ; Division of Medical Oncology, School of Medicine, University of Colorado Denver, Anschutz Medical Campus Aurora, CO 80045 USA.

Prostate cancer is the most common non-cutaneous cancer in US men and mainly affects elderly patients, with most new diagnoses occurring in those over 65. As the geriatric population in the US continues to grow, the incidence of this disease is likewise expected to rise. Many older patients are diagnosed with advanced disease or are treated only when their disease becomes symptomatic or metastatic. The treatment options for advanced prostate cancer have increased dramatically in the last decade. It is important to understand the nuances of caring for an elderly cancer patient in order to optimally treat prostate cancer, such as the importance of using a geriatric assessment to uncover overlooked or under-reported vulnerabilities. In addition, many of the newly approved agents for the treatment of advanced prostate cancer have a unique mechanism of action and toxicities that warrant consideration when choosing therapies for older patients. This review focuses on the importance of a geriatric assessment as well as the considerations of treating elderly patients with the newer agents approved for prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12703/P6-33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017909PMC
June 2014

Sequencing medical therapy in prostate cancer: not as easy as 1-2-3.

Oncology (Williston Park) 2013 Nov;27(11):1158-60

University of Colorado Cancer Center, Aurora Colorado, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
November 2013

Collision renal cell papillary and medullary carcinoma in a 66-year-old man.

Oncology (Williston Park) 2013 Sep;27(9):893, 896, 898

Division of Medical Oncology, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
September 2013

Targeted therapy in advanced urothelial carcinoma.

Oncology (Williston Park) 2013 Mar;27(3):219-26

Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado, USA.

Urothelial carcinoma (UC) is a common and deadly cancer in the United States. While molecularly targeted therapies have been integrated into the standard-of-care management of other solid tumors in recent years, the use of targeted therapy in UC has lagged behind. Accordingly, the management of advanced disease, along with outcomes, has remained largely unchanged for the past 2 decades. Despite the lack of new agents in the clinic, preclinical and early clinical studies have demonstrated that numerous potentially"targetable" molecular pathways exist, including the epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), human epidermal growth factor receptor 2 (HER2/neu), and insulin-like growth factor 1 receptor (IGF1R) pathways. This review focuses on targeted therapies related to these pathways of interest for the treatment of advanced UC, describing the evidence to support further investigation of these approaches. Notably, the identification and validation of new agents will only occur through accrual to urothelial cancer trials designed to answer these questions, which will require the support of the entire urologic community.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2013

Optimal management of recurrent prostate cancer in older patients.

Drugs Aging 2012 Nov;29(11):871-83

Division of Medical Oncology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, 80045-0511, USA.

With a large, aging population in the USA and continued prolongation of life expectancy, treatment of cancer in the elderly will continue to be of importance. The most common cancer in men is prostate cancer, which is most often diagnosed in those over the age of 65 years. Initial therapies for prostate cancer are local treatments in those with localized disease and for whom definitive therapy is appropriate. Optimal treatment of an older patient with recurrent prostate cancer now involves more of a decision process than treatment has in the past, with the recent approval of several new medical agents for advanced prostate cancer. Through this article we will focus on treatment options for recurrent prostate cancer, keeping in mind the unique characteristics of the elderly population. A majority of the discussion will focus on many of the newly approved agents used to treat castration-resistant prostate cancer, and exciting agents currently under investigation. Improved androgen blockade has improved overall survival in patients with metastatic disease but carries many of the same adverse effects as previous agents. Newer approaches with immunotherapy, radiopharmaceuticals, or second-generation androgen receptor blockers introduce a different adverse-effect profile for older patients. As data matures, these too may improve survival for patients with metastatic disease. Throughout all stages of disease, one must keep in mind the unique needs of an older patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40266-012-0021-4DOI Listing
November 2012