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Bcl-2 protein is upregulated in a wide variety of lymphoid malignancies,including chronic lymphocytic leukemia (CLL). The proteinis thought to be responsible for maintaining the viability of malignantlymphoid cells and may contribute to chemotherapy and radiotherapyresistance. Previous studies have shown that reduction of bcl-2 expressionby antisense therapy sensitizes cells to chemotherapy-inducedapoptosis. In vitro, the Bcl-2 antisense drug oblimersen sodium(Genasense, previously known as G3139) enhances the apoptotic responsein CLL cells to fludarabine (Fludara), corticosteroids,alemtuzumab (Campath), and rituximab (Rituxan). A phase I trial inpatients with refractory/relapsed CLL showed that patients with CLLwere more sensitive to oblimersen than patients with solid tumors. Themaximum tolerated oblimersen dose was 3 mg/kg/d, and the most commondose-limiting reaction was hypotension, frequently in associationwith high spiking fever. In this study, oblimersen displayed limited singleagentactivity, including tumor lysis syndrome, transient decreases incirculating CLL cells, and reduction of splenomegaly and size of lymphnodes. Major responses were observed in 9% of patients. Subsequently,a phase III trial evaluating fludarabine and cyclophosphamide with orwithout oblimersen (3 mg/kg/d for 7 days) was initiated in patients withrelapsed or refractory CLL. This trial recently completed accrual of241 patients.

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Here we review some of the most significant changes in the surgical management of melanoma that have reduced morbidity and thereby improved patient outcomes.

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In this interview we discuss how quality-of-life information from patients with lung cancer can be used to help guide treatment and inform outcomes.

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Few areas in breast disease elicit as much controversy as the management of DCIS. The review by Sanders and Simpson, “Can We Know What to Do When DCIS Is Diagnosed?”

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Panelists discuss how thoracic oncologists are adapting to a rapidly evolving treatment landscape for lung cancer, focusing on the integration of novel therapies and the importance of biomarker-driven approaches in patient care.

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Early clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect.

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Because of the high rate of distant disease recurrence, the 5-yearsurvival of patients who have undergone complete surgical resectionof localized non–small-cell lung cancer (NSCLC) is approximately 50%.Initial results from early studies of adjuvant postoperative chemotherapyreported an adverse effect of alkylating agent and older chemotherapyregimens on survival. Cisplatin-based combinations were the first toshow a survival advantage. A 1995 meta-analysis of these studies suggesteda 13% reduction in the hazard ratio for death (HR = 0.87), leadingto a 5% survival benefit at 5 years. Still, these trials involved limitednumbers of patients (N = 1,394), and the results failed to reach statisticalsignificance (P = .08). Of the five largest subsequent randomizedtrials of platinum-based adjuvant therapy, three showed a significantsurvival advantage. Although it is impossible to determine the reasonsfor the differing outcomes of these studies, several key features distinguishthem, and the data suggest that medically fit patients with resectedstage IB or II NSCLC should be offered chemotherapy with a platinum/new drug combination.

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The review by Drs. Boumber and Issa of epigenetic drugs that target human cancers nicely summarizes recent progress in this hot area and points out future lines of investigation.

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Locally advanced adenocarcinoma of the prostate (American Urological Association stages B2, C; American Joint Committee on Cancer stages T2c, T3) has been difficult to control by either external-beam irradiation or

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A 74-year-old man presented with a 2.5-cm ulcerated mass occupying the middle third of his left outer ear, approximating the helical rim.

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Drs. Bystryn and Reynoldspresent an overview of melanomavaccines, including atheoretical rationale to support the approach,criteria for an effective vaccine,and a discussion of the challengesto optimal vaccine design. Results ofclinical trials where vaccine-inducedimmune responses correlated withimproved clinical outcome are discussed,as well as limitations of monitoringvaccine-induced immuneresponses. A series of randomized, concurrentlycontrolled trials with complex,polyvalent whole-cell vaccines,extracts, lysates, or shed antigens arereviewed. The authors conclude thatmelanoma vaccines' "potentially mostsignificant application" may be the preventionof melanoma in individuals athigh risk of developing the disease.Their review discusses the generallyaccepted rationale for selecting vaccineantigens and does a thoughtfuljob of reviewing the current state ofcomplex melanoma vaccines.

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Thousands of practice guidelines/practice parameters have been published by various professional organizations. The American Medical Association,[1] American College of Physicians,[2,3] and others[4-6] have written extensively about

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Patient selection based on a much more comprehensive biologic assessment of both host and tumor is likely the key to further advances in the treatment of all bladder cancer patients. Until such time, there can be no compromise in the careful application of the rigorous therapy required to optimize outcomes.

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The relationships between psychological variables and the presence of cancer, its prediction, and the prediction of cancer mortality and course of disease have been studied extensively. From a limited list of about 50 such

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The article by Posadas and Figlin on systemic therapy in advanced renal cell carcinoma (RCC) provides a very interesting and comprehensive review of our current knowledge concerning the treatment of RCC.

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Nearly 150,000 people will be diagnosed with colorectal cancer in the United States in 2006. The impact of this diagnosis will be felt by countless family members, coworkers, and friends. Although screening tests for colorectal cancer have been available and encouraged by medical associations such as the American Cancer Society (ACS) and others, public awareness and compliance has been dismal.

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Beyond the current recommendations for management of chemotherapy-induced nausea and vomiting, recent research has shown significant improvement in emesis control with use of triplet therapy using dexamethasone, an NK1 receptor antagonist, and a 5-HT3 receptor antagonist in patients undergoing non–anthracycline-plus-cyclophosphamide-based moderately emetogenic chemotherapy.

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If doctors were trained in communication skills, then quackery would diminish greatly. When you are told what day you are going to die and all hope is taken away, why not seek alternative therapies?

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This management guide covers the risk factors, symptoms, diagnosis, staging, and treatment of liver, gallbladder, and biliary tract cancers using radiation, surgery, and medical treatment.

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Elderly patients may have several such comorbidities, but their impact on normal life is minimal-and so most of these patients may receive a curative treatment such as R-CHOP. Very elderly patients have more comorbidities with greater impact, with the result that some of their vital organs exhibit functional deficiency.

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For appropriate older women screening provides a benefit in this age group by identifying early-stage breast cancer.

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This article represents the consensus opinion of an expert panel and may be used to inform clinical recommendations in vaginal cancer management.

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Schrader and colleagues provide four compelling examples of the power of genetic testing to impact medical management for probands and their family members.

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The care of a pregnant breast cancer patient is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. For the woman in this situation, the emotions usually

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Eliminating cancer disparities-not only for racial/minority groups but for all underserved populations-must be a priority for those involved in cancer care. For individual practitioners, the first step in addressing disparities is accomplished through understanding the possibility that disparities exist in varying depth and complexity for each racial or ethnic minority patient.

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Recently published research questions the need for the advised restriction against the use of soyfoods by women with a history of breast cancer.

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The article by Khatcheressian and colleagues addresses the important topic of futility in chemotherapy use. While extensive previous literature has addressed the use of futile treatment by oncologists, Khatcheressian and coauthors pose interesting perspectives on patient persistence in seeking futile treatment.

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Anaplastic large cell lymphoma (ALCL) is a biologic and clinically heterogenous subtype of T-cell lymphoma. Clinically, ALCL may present as localized (primary) cutaneous disease or widespread systemic disease. These two forms of ALCL are distinct entities with different clinical and biologic features. Both types share similar histology, however, with cohesive sheets of large lymphoid cells expressing the Ki-1 (CD30) molecule. Primary cutaneous ALCL (C-ALCL) is part of the spectrum of CD30+ lymphoproliferative diseases of the skin including lymphomatoid papulosis. Using conservative measures, 5-year disease-free survival rates are>90%. The systemic ALCL type is an aggressive lymphoma that may secondarily involve the skin, in addition to other extranodal sites. Further, systemic ALCL may be divided based on the expression of anaplastic lymphoma kinase (ALK) protein, which is activated most frequently through the nonrandom t(2;5) chromosome translocation, causing the fusion of the nucleophosmin (NPM) gene located at 5q35 to 2p23 encoding the receptor tyrosine kinase ALK. Systemic ALK+ ALCLs have improved prognosis compared with ALK-negative ALCL, although both subtypes warrant treatment with polychemotherapy. Allogeneic and, to a lesser extent, autologous stem cell transplantation play a role in relapsed disease, while the benefit of upfront transplant is not clearly defined. Treatment options for relapsed patients include agents such as pralatrexate (Folotyn) and vinblastine. In addition, a multitude of novel therapeutics are being studied, including anti-CD30 antibodies, histone deacetylase inhibitors, immunomodulatory drugs, proteasome inhibitors, and inhibitors of ALK and its downstream signaling pathways. Continued clinical trial involvement by oncologists and patients is imperative to improve the outcomes for this malignancy.

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Nursing management of patients with advanced malignancies presents a formidable challenge. In addition to the discomfort and debilitation these diseases can cause, side effects of traditional treatment modalities such as surgery, chemotherapy, and radiation may lead to severe and sometimes fatal sequelae. New targeted therapies promise an effective treatment with more easily tolerated and managed side effects. Basic understanding of the drugs' mechanism of action contributes to the successful management of the toxicities that can be manifested. Effective patient education results in improved compliance with treatment regimens and potentially improved clinical outcomes. Nursing intervention remains a vital component in the successful use of these novel agents.