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New Treatments for Multiple MyelomaIn 2004, multiple myeloma was diagnosed in more than 15,000 peoplein the United States and will account for approximately 20% of deathsdue to hematologic malignancies. Although traditional therapies suchas melphalan (Alkeran)/prednisone, combination chemotherapy withVAD (vincristine, doxorubicin [Adriamycin], and dexamethasone), andhigh-dose chemotherapy with stem cell transplantation have shownsome success, median survival remains between 3 to 5 years. Treatmentoptions for patients with multiple myeloma have increased in recentyears, with the promise of improvement in survival. New agents, suchas the proteasome inhibitor bortezomib (Velcade), the antiangiogenicand immunomodulator thalidomide (Thalomid) and its analogs, suchas lenalidomide (Revlimid), together with other small molecules, includingarsenic trioxide (Trisenox), and other targeted therapies, havebeen studied alone and in combination with other antineoplastic therapies,either as induction therapy prior to stem cell transplantation or inpatients with relapsed disease. Bortezomib recently was approved inthe United States for the treatment of multiple myeloma in patientswho have received at least one prior therapy. The use of bortezomibbasedregimens as front-line therapy as well as the use of other agentsin multiple myeloma remain under investigation, and approvals forboth thalidomide and lenalidomide are hoped for soon, with the overallprospect of patient outcome continuing to be increasingly positive.
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Radiofrequency Ablation in Lung Cancer: Promising Results in Safety and EfficacyOnly about 15% of patients diagnosed with lung carcinoma eachyear are surgical candidates, either due to advanced disease orcomorbidities. The past decade has seen the emergence of minimallyinvasive therapies using thermal energy sources: radiofrequency,cryoablation, focused ultrasound, laser, and microwave; radiofrequencyablation (RFA) is the best developed of these. Radiofrequency ablationis safe and technically highly successful in terms of initial ablation.Long-term local control or complete necrosis rates drop considerablywhen tumors are larger than 3 cm, although repeat ablations can beperformed. Patients with lung metastases tend to fare better with RFlung ablation than those with primary lung carcinoma in terms of localcontrol, but it is unclear if this is related to smaller tumor size at time oftreatment, lesion size uniformity, and sphericity with lung metastases,or to differences in patterns of pathologic spread of disease. The effectsof RFA on quality of life, particularly dyspnea and pain, as well aslong-term outcome studies are generally lacking. Even so, the resultsregarding RF lung ablation are comparable to other therapies currentlyavailable, particularly for the conventionally unresectable or high-risklung cancer population. With refinements in technology, patient selection,clinical applications, and methods of follow-up, RFA will continueto flourish as a potentially viable stand-alone or complementarytherapy for both primary and secondary lung malignancies in standardand high-risk populations.
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Emotional and Behavioral Responses to Genetic Testing for Susceptibility to CancerAs genetic testing for susceptibility to cancer becomes more widely available, cancer-care providers will become more involved in counseling patients about cancer risks and the meaning of genetic test results. As a result, oncologists and oncology nurses need to be aware of the unique psychological issues and challenges posed by genetic testing for cancer susceptibility. This paper first describes a psychological profile of individuals who are likely to opt for such testing, based on extrapolation from studies of people at high risk of cancer.
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The Radiologic Appearance of Lung CancerThe article by O'Donovan discusses the radiologic appearance of lung cancer, with particular emphasis on the radiographic appearance and work-up of solitary pulmonary nodules (SPNs).
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Clinical Status of Laparoscopic Bowel Surgery for GI MalignancyLaparoscopic surgery for colorectal malignancy is an important topic because of its potential advantages and its oncologic controversies. Drs. Wexner and Hwang have prepared a comprehensive review of the current status of laparoscopic colorectal surgery for malignancy. The relative merits of the new procedure are discussed from a number of perspectives, including the technical aspects of laparoscopic bowel resection, oncologic concerns, and experimental and theoretical effects on tumor growth and host immunity.
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Commentary (Thompson): Update on Radiation Therapy for Endometrial CancerDr. Grigsby does an excellent job of summarizing the accepted, stage-by-stage treatment recommendations as well as the controversies surrounding the treatment of endometrial carcinoma. This review is both important and timely, as we have seen the incidence of endometrial cancer increase over the past few years to the point where it is now the most common gynecologic malignancy.
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BMT for Severe Autoimmune Diseases: An Idea Whose Time Has ComeThe article by Dr. Burt provides an excellent summary of the rationale for using high-dose therapy with autologous or allogeneic bone marrow transplantation (BMT) in patients with severe autoimmune diseases (SADS). The article also describes the approach to BMT adopted by Dr. Burt and colleagues at Northwestern University. Enthusiasm for this form of therapy has been contagious, and numerous US investigators have initiated similar trials, which are outlined in Table 1 of the article.
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Role of Laparoscopy in the Staging of Gastrointestinal CancerAccurate staging plays a primary role in determining the appropriate treatment of gastrointestinal malignancies. Recently, laparoscopy has emerged as a staging modality that is more sensitive and specific in staging most
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mTOR Inhibitors in the Treatment of Breast CancerEfforts to identify clinical biomarkers of response or resistance to mTOR inhibitors are ongoing. This review will summarize results of preclinical and clinical studies as well as ongoing clinical trials with mTOR or dual PI3K/mTOR inhibitors.
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Risk of Endometrial Cancer After Tamoxifen TreatmentA total of 18 studies have been published concerning the possible relationship of tamoxifen to endometrial
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Intravesical Therapy for Superficial Bladder CancerThe intravesical instillation of therapeutic agents for the treatment of localized bladder cancer began in 1903 when Herring[1] summarized his experience with silver nitrate. Since then, intravesical chemotherapy and immunotherapy have emerged as
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Hormone-Refractory Prostate Cancer: Choosing the Appropriate Treatment OptionHormone-refractory prostate cancer (HRCaP) is both heterogeneous and lethal. Multiple treatment options exist, including secondary hormonal manipulations, chemotherapy, experimental options, and best supportive care. Choosing the appropriate therapy for an individual patient depends on several important clinical factors such as the presence or absence of symptomatic metastatic disease, age and comorbidities, and prostate-specific antigen velocity. While only docetaxel (Taxotere)-based chemotherapy has been proven to improve survival in this setting, a wide range of therapies may be effective for any individual. Palliative maneuvers, such as external-beam radiation, bisphosphonate therapy, radiopharmaceuticals, and pain management are critical for appropriate patient management. Several promising novel therapies are in late-stage testing and will hopefully provide more treatment options for these patients.
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Molecular Staging of Prostate Cancer: Dream or Reality?The promise of using reverse transcriptase–polymerase chain reaction (RT-PCR) technology for the detection of circulating prostate cancer cells in peripheral blood, although technically feasible at the molecular level, has proven clinically impractical for routine implementation in patient management. Reverse transcriptase–polymerase chain reaction has been successfully applied to detect and quantify (relatively speaking) genes that are differentially expressed in cells and tissues obtained from patients during various stages of malignant growth. In addition, the method has been applied to the detection of circulating cancer cells in peripheral blood using highly specific primer sets for specific molecular targets. These include epithelial cell cytokeratins for breast cancer, as well as enzymes, such as tyrosinase for melanoma and prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) for prostate cancer, using either nonnested or nested methodologies.
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Advances in the Treatment of Gynecologic MalignanciesOver the past few decades, we have gained a better understanding of the risk factors associated with the recurrence of endometrial cancer. Adjuvant postoperative radiotherapy in an intermediate-risk group of
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AIDS Malignancies in the Era of Highly Active Antiretroviral TherapyA dramatic spike in the incidence of Kaposi’s sarcoma (KS) in never-married men in New York and California in 1981 was one of the first indications of a new disease now known as acquired immunodeficiency syndrome (AIDS). We now appreciate a number of mechanisms by which human immunodeficiency virus (HIV) infection contributes to the pathogenesis of these tumors. The article by Drs. Gates and Kaplan provides an excellent review of changes in the epidemiology, presentation, and treatment of these tumors since the development of potent combination anti-HIV therapy.
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Management of Bispecific Toxicities and Final Thoughts on Treatments in MMClosing out the panel discussion, experts review the management of bispecific-related toxicities and share their final thoughts on treating patients with multiple myeloma.
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Improving the Therapeutic Ratio in Hodgkin Lymphoma Through the Use of Proton TherapyThis review addresses the rationale and evidence for-and the challenges, cost implications, and future development of-proton therapy as an important part of the treatment strategy in Hodgkin lymphoma.
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Economic and Quality of Life Outcomes: Managed Care PerspectivesA variety of economic factors have created a growing demand for health care reform and the rapid expansion of managed care plans. Absence of a clear, commonly accepted definition of managed care constitutes one of the
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The 340b Drug Discount Program: Oncology's Optical IllusionThe historical rationale for the 340b program is a good one: indigent patients do need reliable access to prescription drugs, and entities meeting this need should be supported. However, the evolution of the 340b program has strayed widely from its original intent.
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Biphenotypic Extramedullary Blast Crisis of Chronic Myeloid Leukemia With Variant Philadelphia Chromosome TranslocationA 45-year-old man with a known history of rheumatic fever and aortic valve replacement 15 years earlier presented with the chief complaint of a 1-month history of progressive, intense, nonmechanical lumbar pain.
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Mini Quiz: Motivational PharmacotherapyLearn about what motivational pharmacology is and is not in this quiz.
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Principles of Chemoradiation: Theoretical and Practical ConsiderationsChemotherapy agents known to enhance the effects of radiation in preclinical studies have been used concurrently with radiotherapy in numerous clinical trials with the prospect of further enhancing radiation-induced
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Is This a True Renaissance for the Treatment of Prostate Cancer?The article by Rove et al represents a comprehensive review of the recent clinical advances in the treatment of metastatic, castrate-refractory prostate cancer. The therapeutic armamentarium for the treatment of prostate cancer remains limited compared to other malignancies, such as breast cancer. It took approximately 14 years after mitoxantrone data emerged for us to see the approval of another chemotherapy agent, docetaxel. The successful outcome of recent clinical trials confirms that true advancement in prostate cancer treatment can be achieved by rational and rigorous clinical testing, but participation in prostate cancer clinical trials remains low, especially participation by African-American patients. Research study enrollment should be a high priority for those health care professionals who treat this disease.
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Management of Leptomeningeal Disease From Solid TumorsMetastasis of solid tumors to the cerebrospinal fluid is a serious complication of cancer. Although it can occur with any type of cancer, tumors with a high propensity for CNS involvement (brain metastases) are the most likely to spread to the cerebrospinal fluid.
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Intraperitoneal Drug Delivery for Ovarian Cancer: Why, How, Who, What, and When?Epithelial ovarian cancer (EOC) spreads prominently within the peritoneal cavity. In fact, we now know that high-grade serous cancers are often of tubal origin, and their presentation as tubo-ovarian masses renders it likely that intraperitoneal spread occurs as an early event in their clinical evolution.
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Mutated ras as a Predictor of Response: Is It Ready for the Clinic?Preliminary results from two trials presented at the 44th Annual Meeting of ASCO in Chicago have consolidated the role of K-ras as a biomarker of nonresponse to cetuximab and panitumumab in metastatic colorectal cancer (mCRC). The phase III CRYSTAL and OPUS trials presented unplanned subgroup analyses of the correlation of K-ras status with response to therapy with first-line FOLFIRI or FOLFOX, respectively, with or without cetuximab in patients with mCRC. Both studies demonstrated a clear benefit with the addition of cetuximab in K-ras WT patients.
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School Skin Cancer Programs Evolving to Include ComputersSkin cancer is the most common malignancy in the United States, with approximately 1 million cases being diagnosed in 1997.[1] Of these cases, more than 40,000 will be classified as malignant melanoma, the most serious and aggressive form of skin cancer.[1] The worldwide incidence of melanoma is increasing more rapidly than any other form of cancer, and has shown an increase of about 4% per year in the United States.[1,2]
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Giving Honest Information to Patients With Advanced Cancer Maintains HopeOncologists often do not give honest prognostic and treatment-effect information to patients with advanced disease, trying not to “take away hope.” The authors, however, find that hope is maintained when patients with advanced cancer are given truthful prognostic and treatment information, even when the news is bad.
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Management of Marginal Zone LymphomaMZL comprises three different entities that require integration of clinical and pathologic features to make a diagnosis. Treatment is chosen and initiated on the basis of presentation, symptoms, and underlying subtype.
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Perspectives on Salvage Therapy for Non–Small-Cell Lung CancerPlatinum-based chemotherapy offers a modest survival advantage overbest supportive care in chemotherapy-naive patients with a good performancestatus and advanced/metastatic non–small-cell lung cancer(NSCLC). Despite the survival benefit associated with first-line chemotherapy,the majority of patients will experience relapse or disease progression.In clinical practice, an increasing number of patients maintaina good performance status after first-line treatment and are eligible forfurther treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every3 weeks has been the standard of care for second-line chemotherapy sincethe year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolateagent with single-agent activity in first- and second-line treatment ofNSCLC. A large phase III study comparing docetaxel to pemetrexed insecond-line therapy demonstrated that pemetrexed is equally active andless toxic than docetaxel. Based on these results, pemetrexed is a reasonablesecond-line chemotherapy option for patients with recurrent, advancedNSCLC. Progress made in the field of molecular biology has led to theidentification of drugs active against specific cellular targets. Gefitinib(Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitorsof the epidermal growth factor receptor. Phase II and III trialshave demonstrated that these agents are active particularly in a subgroupof patients with specific biologic characteristics. Both drugs have beenapproved for the treatment of pretreated NSCLC. Other drugs, such ascetuximab (Erbitux) and bevacizumab (Avastin) have shown promisingactivity in NSCLC and are currently being tested in clinical trials.
