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It’s Time for Clinicians to Reconsider Their Proscription Against the Use of Soyfoods by Breast Cancer PatientsRecently 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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Update on Adjuvant Chemotherapy for Early Breast CancerAdjuvant chemotherapy represents a significant advance in the management of early-stage breast cancer and, as such, has saved many lives. Worldwide, adjuvant chemotherapy has benefitted all groups tested, including
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HDAC Inhibitor Research: Still in Its InfancyShabason et al have written a thoughtful review of an exciting new class of agents, histone deacetylase (HDAC) inhibitors. While the authors focus primarily on the role of HDAC inhibitors in combination with radiation therapy, we would like to highlight some potential strategies combining these agents with systemic therapies for the treatment of cancer.
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Molecular Markers for Diagnosis, Staging, and Prognosis of Bladder CancerConventional histopathologic evaluation of bladder cancer, encompassing tumor grade and stage, is inadequate to accurately predict the behavior of most bladder tumors. Intense research efforts are under way to identify and
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Commentary (Fesen): NCI's Cancer Information Systems-Bringing Medical Knowledge to CliniciansHubbard, Martin, and Thurn describe PDQ, CANCERLIT, and other International Cancer Information Center (ICIC) programs that bring cancer information to health professionals, patients, and policy makers. PDQ (Physician Data Query), the cancer information "knowledge base" of the ICIC includes information on cancer treatment, screening, and prevention, as
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Treatment Recommendations for Anaplastic Oligodendrogliomas That Are CodeletedAlthough important questions still remain regarding chemotherapy choice, sequence, and dosing, the answers to which will require additional large phase III trials, radiotherapy alone is no longer appropriate therapy for 1p/19q codeleted anaplastic oligodendrogliomas.
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Managing Non-Small-Cell Lung Cancer: Further ConsiderationsNon-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Before 1980, radiotherapy was considered the only real recourse in advanced disease. In 1995, a landmark meta-analysis of trials conducted in the 1980s and early 1990s demonstrated a survival benefit with platinum-based chemotherapy. Newer chemotherapy agents and improved supportive care measures have allowed more patients to benefit from chemotherapy with reduced toxicity. Concurrent platinum-based chemotherapy and radiotherapy has improved the survival in stage III disease, and recently chemotherapy has also demonstrated improved survival in resected early-stage disease. The majority of patients still present with advanced unresec disease for whom the prognosis remains poor, but for key subpopulations the outlook has improved markedly since the emergence of targeted therapies directed against the epidermal growth factor receptor and vascular endothelial growth factor receptor pathways. Patient selection and the incorporation of targeted therapies with cytotoxic chemotherapy are the focus of many ongoing studies, and there is an abundance of new agents undergoing clinical trials. Together, these developments have moved us away from the nihilism of 20 years ago into an era of unprecedented optimism in taking on the many remaining challenges of managing NSCLC in the 21st century.
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Would Oncologists Want Chemotherapy If They Had Non-Small-Cell Lung Cancer?In 1985, a survey found that only about one-third of physicians and oncology nurses would have consented to chemotherapy for non-small-cell lung cancer. In response to statements made at a recent American Society of Oncology (ASCO) Board of Directors meeting questioning whether these data are still valid, Dr. Smith and colleagues conducted a new survey of oncologists attending a 1997 National Comprehensive Cancer Network (NCCN) annual meeting. The results of that survey are summarized and analyzed.
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Controversies in the Pathology of Thymoma Viewed Through the Prism of Evidence-Based PathologyThymomas are uncommon neoplasms that have generated considerable controversy among pathologists. The following questions can be used to evaluate the evidence supporting current concepts about the pathology of thymomas and the clinical applicability of those concepts.
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Inhibition of Poly(ADP)-Ribose Polymerase as a Therapeutic Strategy for Breast CancerAs knowledge increases about the processes underlying cancer, it is becoming feasible to design “targeted therapies” directed toward specific pathways that are critical to the genesis or maintenance of the malignant phenotype. Poly(ADP-ribose) polymerase (PARP) inhibitors are an example of this new framework. DNA damage repair is a complex and multifaceted process that is critical to cell survival. Members of the PARP family are central to specific DNA damage repair pathways, particularly the base excision repair (BER) pathway. PARP inhibition, with subsequent impairment of the BER mechanism, may enhance the cytotoxicity of agents that generate single-strand breaks in DNA, such as radiation and certain chemotherapy drugs. In addition, PARP inhibitors may induce death through “synthetic lethality” if the DNA repair mechanisms that rescue BER-deficient cells are themselves impaired. This mechanism is thought to underlie the impressive results of PARP inhibition in BRCA-associated breast and ovarian cancer, and may also account for the reported benefit of this approach in “triple-negative” breast cancer. This review will examine the current understanding of PARP inhibition as a treatment for breast cancer, ongoing clinical trials, and future directions for this new approach.
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Molecular Monitoring of Cell-Free Circulating Tumor DNA in Non-Hodgkin LymphomaIn this review, we discuss the potential applications of monitoring ctDNA in patients with diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma.
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The Long Road-and the High Road-to Successful Implementation of OncoEMRWhat distinguishes those practices that are successful in their use of the EMR is their commitment to the product and their recognition that it is the central element in the treatment of their patients.
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Minimizing Oral Complications of Cancer TreatmentAggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae have become often overlooked priorities of the treatment team.
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A Patient With Metastatic Melanoma of the Small BowelMelanoma frequently metastasizes to the small bowel. In this installment of Clinical Quandaries, we describe the case of 74-year-old man who presented with this rare but well described manifestation of malignant melanoma
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Radioimmunotherapy: An Underutilized AlternativeTositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.
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Counseling Cancer Patients About Changes in Sexual FunctionCancer treatments often cause sexual dysfunctions that remain severe long after therapy is over. Nevertheless, sexual counseling is not routinely provided in most oncology treatment settings. Most patients and their partners can benefit from brief counseling that includes education on the impact of cancer treatment on sexual functioning; suggestions on resuming sex comfortably and improving sexual communication; advice on how to mitigate the effects of physical handicaps, such as having an ostomy, on sexuality; and self-help strategies to overcome specific sexual problems, such as pain with intercourse or loss of sexual desire. Brief counseling can be provided by one of the allied health professionals on the oncology treatment team. A minority of patients will need specialized, intensive medical or psychological treatment for a sexual dysfunction. In a large cancer center, such treatment could be provided as part of a reproductive health clinic serving the special needs of cancer patients. In smaller settings, the oncologist should build a referral network of specialists. Not all managed care organizations reimburse for these services, however. [ONCCOLOGY 13(11):1585-1591, 1999]
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The Multidisciplinary Management of Paragangliomas of the Head and Neck, Part 2Paragangliomas most commonly occur in the carotid body, jugulotympanicarea, and vagus nerve but have also been reported in otherareas of the head and neck. These tumors are highly vascular andcharacteristically have early blood vessel and neural involvement,making their treatment particularly challenging. Surgery has traditionallybeen the preferred method of treatment, especially in light of recentadvances in technique. However, compared to radiation therapy, it canresult in a higher incidence of cranial nerve dysfunction. Radiationtherapy has the advantage of avoiding the increased morbidity ofsurgery while offering an equal possibility of cure. Part 2 of this articlediscusses radiation therapy as primary treatment of patients who areineligible for surgery and the elderly and infirm. Results with radiotherapyare comparable to those achieved with surgery. The efficacy ofsalvage therapy with either surgery or radiation is discussed, and atreatment algorithm for these tumors is proposed.
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It’s Tough to Make Predictions, Especially About the Future ... of Rectal CancerBy adjusting the sequencing of currently available treatments, improved compliance with therapy is ensured, and novel scientific and clinically relevant hypotheses can be further explored.
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Commentary (Soloway): Management of Patients With Muscle-Invasive and Metastatic Bladder CancerHigh-grade urothelial cancer ofthe bladder is not only relativelycommon but unfortunately,is frequently lethal. These tumorsare often diagnosed when thetumors have already invaded the wallof the bladder. Even when they arediagnosed at a time when they areconfined to the mucosa or lamina propria,patients may not respond to abladder-preservation approach. Oftena radical cystectomy with urinary diversionis either not offered at all or notconsidered until the cancer has invadeddeep into the muscularis propria andlocal treatment fails.
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Endoscopic Ultrasound in the Diagnosis and Staging of Pancreatic CancerThe article by Drs. Levy and Wiersema is an excellent overview of the indications, technical nuances, and efficacy of endoscopic ultrasound in the diagnosis and staging of pancreatic neoplasms. Endoscopic ultrasonography was introduced into the diagnostic armamentarium for gastroenterology approximately 15 years ago. Although the literature suggests a general increase in the utility and experience with endoscopic ultrasound, the technique remains most effective in the hands of experienced experts like Drs. Levy and Wiersema. Their article is a complete and thorough review of the indications and expected accuracy of the technique when evaluating a variety of different pancreatic lesions.
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The Allegheny General Modification of the Harvard Breast Cosmesis Scale for the Retreated BreastRepeat lumpectomy and retreatment radiotherapy following ipsilateral breast tumor recurrence (IBTR) by either external-beam irradiation or brachytherapy in lieu of salvage mastectomy is an area of significant recent clinical interest. Multiple authors have reported their results, with encouraging numbers of patients avoiding mastectomy.[1‑4]
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Monitoring Changes in the Microenvironment During Targeted TherapiesThis review covers progress to date in the identification of molecular targets on blood vessels in cancers, as well as agents that act on those targets, with emphasis on those currently in clinical trials. Current vascular-targeting therapies comprise two general types—antiangiogenic therapy and antivascular therapy. Advances in antiangiogenic therapies, particularly inhibitors of vascular endothelial growth factors and their receptors, have clarified the capacity of these inhibitors to change tumor-associated vessel structure to a more normal state, thereby improving the ability of chemotherapeutics to access the tumors. The responses of other antiangiogenesis target molecules in humans are more complicated; for example, αvβ3 integrins are known to stimulate as well as inhibit angiogenesis, and cleavage of various extracellular proteins/proteoglycans by matrix metalloproteinases produces potent regulators of the angiogenic process. Antivascular therapies disrupt established blood vessels in solid tumors and often involve the use of ligand-based or small-molecule agents. Ligand-based agents, irrespective of the antiangiogenic capacity of the ligand, target antivascular effectors to molecules expressed specifically on blood vessels, such as aminopeptidase N, fibronectin extra-domain B, and prostate-specific membrane antigen. Small-molecule antivascular agents, which are not targeted to molecules on blood vessels, rely on physical differences between the vasculatures in tumors and those in normal tissues.
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Treatment of Adult ALL: More Questions Than AnswersIt is clear that the management of adult patients with ALL is an area in which little progress has been made in the last 30 years. Given the disappointing outcomes, the field is one that lends itself to the study of the incorporation of novel agents, including monoclonal antibodies and tyrosine kinase and proteasome inhibitors, as well as to further study of allogeneic transplant.
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Gemcitabine and UFT Plus Oral Calcium Folinate: Phase I StudyGemcitabine (Gemzar) (2-deoxy-2,2-difluorocytidine) is a new antimetabolite being increasingly used in the treatment of solid tumors. It is an analog of deoxycytidine and cytosine arabinoside (Ara-C) (Figure 1) that has shown significant activity
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Allogeneic Transplantation for Chronic Lymphocytic Leukemia in the Age of Novel Treatment StrategiesThe aim of this review is to summarize the current knowledge on HSCT in CLL and to discuss critically its role in the age of novel treatment strategies.
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Management of Infusion Reactions in Clinical Trials and Beyond: The US and EU PerspectivesInfusion reactions (IRs) can be broadly categorized by their immunologic mechanism. Anaphylaxis is a systemic, immediate hypersensitivity reaction mediated by factors released from interactions between immunoglobulin E (IgE) and mast cells that produce an antigen-antibody reaction.[1] Anaphylactoid reactions can be differentiated from anaphlaxis by the fact that they are not IgE-mediated but rather cytokine-mediated.
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Approaches for Optimal Drug Development and Clinical Trial Design for Breast Cancer Brain MetastasisBrain metastases arising from breast cancer constitute a clinically unmet need and a situation that portends a poor prognosis with few therapeutic options.
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A 72-Year-Old Man With Prostate CancerThe patient, L.E., is a 72-year-old white male who has been under our care for 10 years. He initially presented to our clinic in 1992, with a diagnosis of localized prostate cancer.
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Current Management of Primary Cutaneous CD30+ T-cell Lymphoproliferative DisordersThe purpose of this review is to familiarize oncologists with the clinical and pathologic features of this relatively rare disease spectrum. This should enable appropriate clinical management and reassurance of patients concerned about their prognosis.
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Commentary (Crispens/Rothenberg): Epidermal Growth Factor Receptor Inhibitors for the Treatment of Epithelial Ovarian CancerOvarian cancer is the deadliestof the gynecologic malignancies.Approximately threequartersof patients present with advanced-stage disease. With aggressivecytoreductive surgery followed byplatinum-based chemotherapy, mostpatients will achieve remission. Despitethis initially good response totreatment, most patients experiencerecurrence and ultimately die of theirdisease. Novel treatment strategies areneeded. Molecularly targeted therapiesoffer the promise of improvedefficacy with decreased toxicity. Inthis article, Drs. Stephanie Blank, RichardChang, and Franco Muggiapresent an excellent summary of thecurrent status of epidermal growth factorreceptor (EGFR) inhibitors in thetreatment of ovarian cancer. They describethe promise of these drugs aswell as some of the questions regardingthe best way to integrate theminto therapy for ovarian cancer.
