Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2.

PURPOSE: In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16-20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment. MATERIALS AND METHODS: All sequential treatment naïve mRCC patients treated with HDIL-2 at the University of Utah (1988-2013) and University of Michigan (1997-2013) were included. Best responses on treatment were associated with survival outcomes using log-rank and COX regression with a landmark analysis at 2 months. RESULTS: 391 patients (75 % male; median age 55 years) were included and belonged to the following prognostic risk categories: 20 % good, 64 % intermediate, and 15 % poor. Best responses on treatment were complete response (9 %), partial response (10 %), stable disease (32 %), progressive disease (42 %), and not evaluable for response (7 %). No significant differences in progression-free survival (HR 0.74, 95 % CI 0.48-1.1, p = 0.14) or overall survival (HR 0.66, 95 % CI 0.39-1.09, p = 0.11) were observed between patients achieving partial response versus stable disease. Significant differences in progression-free survival (HR 0.13, 95 % CI 0.09-0.22, p < 0.0001) and overall survival (HR 0.33, 95 % CI 0.23-0.48, p < 0.0001) were observed between patients achieving stable disease compared to those with progressive disease and who were not evaluable. CONCLUSIONS: Survival benefit with HDIL-2 is achieved in ~50 % patients and extends beyond those achieving objective responses.

NCCN Task Force report: optimizing treatment of advanced renal cell carcinoma with molecular targeted therapy.

The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion.

Brachytherapy: Increased Use in Patients With Intermediate- and High-Risk Prostate Cancers.

BACKGROUND: Brachytherapy is a well-established and effective primary treatment modality for low- and favorable intermediate-risk prostate cancers. Although the benefits of brachytherapy in unfavorable intermediate- and high-risk prostate cancers have not been as clear, research suggests that brachytherapy boost may improve biochemical progression-free survival in these patients. OBJECTIVES: This article aims to discuss evidence for the revival of brachytherapy use in unfavorable intermediate- and high-risk prostate cancers and specific nursing implications in the management of these patients. METHODS: The literature on brachytherapy and its use to treat localized prostate cancers was reviewed. FINDINGS: Nurses should be knowledgeable about the indications for brachytherapy, patient eligibility, anticipated side effects, and symptom management.

What kind of rash is it?: deciphering the dermatologic toxicities of biologic and targeted therapies.

An overwhelming number of new agents, including targeted agents with unique mechanisms of action, are available in oncology practice today. Along with the benefit of new treatments for patients comes the unfamiliarity of associated toxicities and learning the best methods to minimize side effects. One such toxicity has been the spectrum of dermatologic reactions from some of the newer small-molecule inhibitors and monoclonal antibodies. Scientific evidence describing the unique rashes and methodologies to treat various cutaneous toxicities with specific agents is extremely limited. This article reviews the currently available literature related to dermatologic toxicities observed with many newer targeted therapies. Current recommendations for management are based on practices implemented during clinical trials and postmarketing practices. Additional research is needed to further elucidate the most efficacious methods for treating side effects observed with newer targeted therapies.

Early Recognition and Management of Posterior Reversible Encephalopathy Syndrome: A Newly Recognized Complication in Patients Receiving Tyrosine Kinase Inhibitors.

BACKGROUND: Adult patients with cancer receiving antineoplastic, targeted, and other immunosuppressive therapies are at risk for severe side effects. Studies link posterior reversible encephalopathy syndrome (PRES) with immunosuppressants used for patients undergoing transplantation, as well as select tyrosine kinase inhibitors (TKIs) and other targeted therapies used in patients with cancer. PRES is a reversible condition with early recognition and management; however, permanent neurologic toxicities have been reported. OBJECTIVES: This article aims to educate oncology nurses on signs, symptoms, and management of PRES in patients receiving TKIs. METHODS: The literature was reviewed to develop an educational session about causes, manifestations, pathophysiology, and management of PRES. Using a case study and flipped classroom model, staff participated in an online lecture and concept engagement exercise. Education for nurses included frequent neurologic and mental status assessments, blood pressure monitoring with mean arterial blood pressure goal, and seizure precautions. Nursing knowledge was evaluated with pre- and post-testing. FINDINGS: Evaluation revealed improved knowledge in recognizing and managing patients with PRES related to TKIs. The flipped classroom approach was perceived as a valuable tool for busy staff nurses.

Combined-modality therapy with gemcitabine and radiotherapy as a bladder preservation strategy: results of a phase I trial.

PURPOSE: We conducted a phase I trial of gemcitabine given twice weekly with concurrent radiotherapy in patients with muscle-invasive bladder cancer. PATIENTS AND METHODS: Eligible patients underwent maximal transurethral resection of their bladder tumors followed by twice-weekly infusion of gemcitabine with 2 Gy/d concurrent radiotherapy to the bladder, for a total of 60 Gy over 6 weeks. The starting dose of gemcitabine was 10 mg/m(2) with subsequent dose levels of 20, 27, 30, and 33 mg/m(2). The primary end point was the determination of the maximum-tolerated dose (MTD) of twice weekly gemcitabine with concurrent radiotherapy. Secondary end points included assessment of toxicity associated with combined-modality therapy and initial assessment of the rate of bladder preservation. RESULTS: Twenty-four patients were enrolled and 23 were assessable for toxicity and response. No significant toxicity was demonstrated at the 10 or 20 mg/m(2) twice-weekly doses. Dose-limiting toxicity (DLT) occurred in two of three patients treated at 33 mg/m(2). Intermediate dose levels of 27 and 30 mg/m(2) were then evaluated. The MTD of gemcitabine was 27 mg/m(2). The DLT was systemic, manifested as an elevation in liver function tests, malaise, and edema. Fifteen of 23 patients (65%) are alive with bladders intact and no evidence of recurrent disease at a median follow-up of 43 months. CONCLUSION: Twice-weekly gemcitabine with concurrent radiotherapy at 2 Gy/d to a total dose of 60 Gy is well-tolerated. The MTD of gemcitabine is 27 mg/m(2). There is a high rate of bladder preservation in this selected group of patients.

Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer.

PURPOSE: Tetrathiomolybdate (TM), a copper-lowering agent, has been shown in preclinical murine tumor models to be antiangiogenic. We evaluated the antitumor activity of TM in patients with advanced kidney cancer in a Phase II trial. EXPERIMENTAL DESIGN: Fifteen patients with advanced kidney cancer were eligible to participate in this trial. TM was initiated p.o. at 40 mg three times a day with meals and 60 mg at bedtime to deplete copper. A target serum ceruloplasmin (CP) level of 5-15 mg/dl was defined as copper depletion. Doses of TM were reduced for grade 3-4 toxicity and to maintain a CP level in the target range. Once copper depletion was attained, patients underwent baseline tumor measurements and then again every 12 weeks for response assessment. Patients not exhibiting progressive disease at 12 weeks after copper depletion continued on treatment. Serum levels of Interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assayed pretreatment and at various time points on treatment. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) was performed on selected patients in an attempt to assess changes in tumor vascularity. RESULTS: All of the patients rapidly became copper depleted. Thirteen patients were evaluable for response. No patient had a complete response or PR. Four patients (31%) had stable disease for at least 6 months during copper depletion (median, 34.5 weeks). TM was well tolerated, with dose reductions most commonly occurring for grade 3-4 granulocytopenia of short duration not associated with febrile episodes. Serum levels of IL-6, IL-8, VEGF, and bFGF did not correlate with clinical activity. Serial DCE-MRI was performed only in four patients, and a decrease in vascularity seemed to correlate with necrosis of a tumor mass associated with tumor growth. CONCLUSIONS: TM is well tolerated and consistently depletes copper as measured by the serum CP level. Clinical activity was limited to stable disease for a median of 34.5 weeks in this Phase II trial in patients with advanced kidney cancer. Serum levels of proangiogenic factors IL-6, IL-8, VEGF, and bFGF may correlate with copper depletion but not with disease stability in this small cohort. TM may have a role in the treatment of kidney cancer in combination with other antiangiogenic therapies.

Symptom clusters in advanced illness.

OBJECTIVES: To review the four sets of symptom clusters commonly seen in patients with advanced illness, and their definitions, associated symptomatology, and management. DATA SOURCES: Research and review articles and textbooks. CONCLUSION: Symptoms of patients with advanced illness tend to occur not isolation, but in symptom clusters. The ability to cluster symptoms in both assessment and management reduces the use of polypharmacy, systemic toxicities, and improves the patient's quality of life. IMPLICATIONS FOR NURSING PRACTICE: It is important that the nurse providing symptom management for the oncology patient understand the importance of clustering certain symptoms together.

Improving documentation of quality measures in the electronic health record.

PURPOSE: Oncology quality measures provide an important tool to evaluate care received by cancer patients. These measures are frequently addressed by oncology nurse practitioners (NPs). NP documentation of quality oncology practice initiative (QOPI) measures in the electronic health record (EHR) is evaluated in this study. DATA SOURCES: NP documentation of specific QOPI measures before and after an educational intervention (EI) was evaluated. EHR shortcuts, called "SmartPhrases," were used to increase efficiency in documentation of these measures. CONCLUSIONS: Preintervention chart audits found compliance <80% in the multiple measurement areas. Following the EI, NPs surveyed identified greater understanding of QOPI measures and an interest in using "SmartPhrases" to aid in measure documentation. The postintervention audit demonstrated improvement in all areas addressed during the EI noting the use of "SmartPhrases" based on descriptive findings. IMPLICATIONS FOR PRACTICE: NPs play a significant role in providing quality care for oncology patients. By increasing knowledge related to the documentation of quality measures and providing tools to increase the efficiency associated with their documentation, a positive impact can be made in efforts to promote quality patient care.

Strengthening end-of-life care through specialty nursing certification.

The purpose of this study was to determine the adequacy of content related to end-of-life (EOL) care in materials used in the nursing certification process across clinical nursing specialties. Thirty-eight certification examination blueprints, 18 specialty nursing scope and standards of practice documents, and 28 specialty nursing core curriculum text books were analyzed by using descriptive statistics to determine the quantity and quality of content related to nine critical areas of EOL content contained in them. Fifteen (38 per cent) of the certification examination blueprints contained at least one of the critical EOL content areas. Eight (44 per cent) of the scope and standards of practice documents contained at least one sentence on EOL care. Seven (25 per cent) of the 28 textbooks contained at least one chapter dedicated to EOL care content, and 129.5 (0.8 per cent) of the 15,706 textbook pages reviewed were dedicated to EOL care content. Expert ratings regarding the overall accuracy, currency, and comprehensiveness of EOL content found in the textbooks were poor to good. An increased focus on EOL care in the nursing specialty certification process is warranted. The content of nursing specialty certification examinations has a direct influence on nursing education as well as a significant impact on nursing practice in clinical specialty areas.

Identifying strategies to optimize care with oral cancer therapy.

More cancer therapies are being administered via an oral route. This paradigm shift in providing cancer treatment has been met with both excitement and significant challenges for oncology practitioners. Multiple factors can impact the ability for patients to initiate and stay on oral cancer therapy. A major factor in patient adherence with oral cancer therapies is management of side effects. Side effects from therapy not only have a negative impact on a patient's quality of life but also can cause serious complications. In addition, they can impact the patient's ability to stay on therapy at optimal doses. New strategies must be designed for educating patients and caregivers, as well as for patient management and follow-up. When side effects are not managed appropriately, patients are less likely to want or be able to adhere to established treatment plans. This article explores several challenges related to the use of oral cancer therapies, with a focus on side effects seen with various classes of new targeted agents. Evidence-based practice strategies and areas in need of additional exploration and research are reviewed.

2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy.

In 2009, the American Society of Clinical Oncology (ASCO) and the Oncology Nursing Society (ONS) published standards for the safe use of parenteral chemotherapy in the outpatient setting, including issues of practitioner orders, preparation, and administration of medication. In 2011, these were updated to include inpatient facilities. In December 2011, a multistakeholder workgroup met to address the issues associated with orally administered antineoplastics, under the leadership of ASCO and ONS. The workgroup participants developed recommended standards, which were presented for public comment. Public comments informed final edits, and the final standards were reviewed and approved by the ASCO and ONS Boards of Directors. Significant newly identified recommendations include those associated with drug prescription and the necessity of ascertaining that prescriptions are filled. In addition, the importance of patient and family education regarding administration schedules, exception procedures, disposal of unused oral medication, and aspects of continuity of care across settings were identified. This article presents the newly developed standards.

2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy.

In 2009, ASCO and the Oncology Nursing Society (ONS) published standards for the safe use of parenteral chemotherapy in the outpatient setting, including issues of practitioner orders, preparation, and administration of medication. In 2011, these were updated to include inpatient facilities. In December 2011, a multistakeholder workgroup met to address the issues associated with orally administered antineoplastics, under the leadership of ASCO and ONS. The workgroup participants developed recommended standards, which were presented for public comment. Public comments informed final edits, and the final standards were reviewed and approved by the ASCO and ONS Boards of Directors. Significant newly identified recommendations include those associated with drug prescription and the necessity of ascertaining that prescriptions are filled. In addition, the importance of patient and family education regarding administration schedules, exception procedures, disposal of unused oral medication, and aspects of continuity of care across settings were identified. This article presents the newly developed standards.

Concepts in advanced renal carcinoma.

OBJECTIVES: Treatment options for advanced renal cell carcinoma have increased dramatically over the past 6 years as a result of improved understanding of the biology of renal cancer and the development of therapies to target pathways relevant to tumor progression. DATA SOURCES: Research-based articles. CONCLUSION: New therapies to treat advanced renal cell cancer results in a need for evidence-based decision making when discussing treatment choices. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of therapeutic strategies, their proposed mechanism of action, potential adverse events, and management strategies provides nurses with a foundation to provide appropriate patient education and effective management of treatment-related side effects, assisting patients to maximize clinical outcomes.

Revisions to the 2009 American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards: expanding the scope to include inpatient settings.

In November 2009, the American Society of Clinical Oncology (ASCO) and the Oncology Nursing Society (ONS) jointly published a set of 31 voluntary chemotherapy safety standards for adult patients with cancer, as the end result of a highly structured, multistakeholder process. The standards were explicitly created to address patient safety in the administration of parenteral and oral chemotherapeutic agents in outpatient oncology settings. In January 2011, a workgroup consisting of ASCO and ONS members was convened to review feedback received since publication of the standards, to address interim changes in practice, and to modify the standards as needed. The most significant change to the standards is to extend their scope to the inpatient setting. This change reflects the conviction that the same standards for chemotherapy administration safety should apply in all settings. The proposed set of standards has been approved by the Board of Directors for both ASCO and ONS and has been posted for public comment. Comments were used as the basis for final editing of the revised standards. The workgroup recognizes that the safety of oral chemotherapy usage, nononcology medication reconciliation, and home chemotherapy administration are not adequately addressed in the original or revised standards. A separate process, cosponsored by ASCO and ONS, will address the development of safety standards for these areas.

Revisions to the 2009 american society of clinical oncology/oncology nursing society chemotherapy administration safety standards: expanding the scope to include inpatient settings.

In November 2009, ASCO and the Oncology Nursing Society (ONS) jointly published a set of 31 voluntary chemotherapy safety standards for adult patients with cancer, as the end result of a highly structured, multistakeholder process. The standards were explicitly created to address patient safety in the administration of parenteral and oral chemotherapeutic agents in outpatient oncology settings. In January 2011, a workgroup consisting of ASCO and ONS members was convened to review feedback received since publication of the standards, to address interim changes in practice, and to modify the standards as needed. The most significant change to the standards is to extend their scope to the inpatient setting. This change reflects the conviction that the same standards for chemotherapy administration safety should apply in all settings. The proposed set of standards has been approved by the Board of Directors for both ASCO and ONS and has been posted for public comment. Comments were used as the basis for final editing of the revised standards. The workgroup recognizes that the safety of oral chemotherapy usage, nononcology medication reconciliation, and home chemotherapy administration are not adequately addressed in the original or revised standards. A separate process, cosponsored by ASCO and ONS, will address the development of safety standards for these areas.

Symptom clusters in individuals living with advanced cancer.

OBJECTIVES: To discuss issues related to symptom clusters in patients living with advanced cancer. DATA SOURCES: Research and review articles. CONCLUSION: The importance for symptom cluster evaluation in oncology has been documented; however, there remain a number of inconsistencies in the literature as to the best way to accomplish this. Individuals living with advanced cancer are often dealing with symptoms from their disease, as well as prior and current therapies. Research related to patients receiving long-term cancer therapies and the symptom clusters experienced by this group of individuals is needed. IMPLICATIONS FOR NURSING PRACTICE: Understanding the intricacies of symptom clusters in this population is an area for future research.

Immune modulation in melanoma and advanced cancer therapy: anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibodies.

Two fully human monoclonal antibodies (mAbs) that target cytotoxic T lymphocyte-associated antigen 4 (CTLA4), tremelimumab and ipilimumab, are in clinical development for the treatment of advanced cancers. The investigational agents enhance T-cell activation and are hypothesized to generate antitumor immunity. Clinical data have shown that treatment with an anti-CTLA4 mAb is tolerable in most patients. In addition, enhanced antitumor activity was observed in some patients. As expected with an agent that enhances the immune response, immune-related adverse events are observed frequently in treated patients. The immune-related adverse events are not observed with standard chemotherapy agents, so many nurses may be unfamiliar with their management. Early recognition and management of immune-related adverse events by oncology nurses is an essential component of effective treatment with an anti-CTLA4 mAb. As immunomodulatory agents such as anti-CTLA4 mAbs are introduced in oncology treatment, nurses will need a greater understanding of the complexities associated with the therapies. Knowledge of immune system functions and how altering the functions may affect the development of side effects will enhance safety and quality of care for patients receiving anti-CTLA4 mAbs.

Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma.

Twenty-four subjects with metastatic melanoma were treated on a randomized Phase Ib trial evaluating an autologous tumor lysate-pulsed dendritic cell (DC) vaccine with or without interleukin (IL)-2. The vaccine consisted of autologous DCs obtained from peripheral blood mononuclear cells (PBMCs) cultured in granulocyte macrophage-colony stimulating factor and IL-4 then pulsed with autologous tumor cell lysate and keyhole limpet hemocyanin (KLH). The primary end points of the trial were safety and immune response to vaccine. Subjects were randomized to vaccine administered every other week times 3, vaccine x 3 followed by low-dose IL-2, or vaccine x 3 followed by high-dose IL-2. Immune response was monitored pretreatment and at 2 and 4 weeks after the third vaccine administration. Disease evaluation was performed at 4 weeks after the third vaccination. Therapy was well tolerated with no local vaccine toxicity greater than grade 1 in any arm. IL-2 toxicity was as expected without additional toxicity from the addition of IL-2 to vaccine. Immune response defined as delayed-type hypersensitivity, PBMC interferon-gamma enzyme-linked immunosorbent spot, and PBMC proliferation, to both autologous tumor and KLH were detected in all arms. Interferon-gamma enzyme-linked immunosorbent spot response to KLH (7 of 10 patients) and autologous tumor (4 of 10 patients) were also detected in subjects with available vaccine draining lymph node cells. There were no differences in immune response between treatment arms. No clinical responses were seen. Autologous tumor lysate-pulsed DC vaccine with or without IL-2 was well tolerated and immunogenic but failed to induce clinical response in patients with advanced melanoma.