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Novel Therapeutic Avenues in Myeloma: Changing the Treatment ParadigmOur better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM—bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM.
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Immunologic and Biologic Properties of the Primary Tumor During Prolonged Neoadjuvant ChemoimmunotherapyPatients with locally advanced cancers have a poor prognosis when treated with radiotherapy and/or surgery alone. The appearance of distant metastases shortly after removal of the primary tumor indicates that micrometastases are already present at the time of diagnosis. We observed a favorable outcome in patients with locally advanced breast cancer treated with a prolonged regimen of neoadjuvant chemotherapy plus granulocyte-macrophage colony-stimulating factor (GM-CSF [Leukine]) compared with patients receiving fewer chemotherapy cycles prior to surgery and radiotherapy. These results can partly be explained by the dose-intensive regimen used, but biologic and immunologic processes inherent to the prolonged presence of the primary tumor and its draining lymph nodes might also contribute to the beneficial outcome. The effects of the prolonged presence of the primary tumor during chemotherapy and GM-CSF administration on the antitumor immune response, and more specifically the functional properties of dendritic cells and T cells, are currently being investigated in a multicenter randomized clinical trial comparing prolonged neoadjuvant chemotherapy plus cytokines with a conventional treatment schedule. Aside from investigations concerning the immune system, other biologic processes, such as tumor angiogenesis, are being investigated at the same time. [ONCOLOGY 16(Suppl 1):32-39, 2002]
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Docetaxel/Doxorubicin/Cyclophosphamide in the Treatment of Metastatic Breast CancerPreliminary results from phase I trials suggest that the use of docetaxel (Taxotere) and doxorubicin (Adriamycin) is a well tolerated and highly active combination regimen for
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Other Fluorinated Pyrimidines in the Treatment of Solid TumorsResearchers, primarily in Japan, Europe, and the United States, have evaluated several new fluorinated pyrimidines in recent years. Most of these drugs are orally active prodrugs of fluorouracil (5-FU), and some also
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Treatment of Advanced Head and Neck Cancer: Past, Present, and FutureBruce Culliney and colleagues have provided a thorough and well written summary of the literature regarding multimodality treatment of patients with locoregionally advanced or unresectable head and neck malignancies. In particular, they offer a detailed outline of recent insights into radiation dosing and fractionation and their optimal use in the combined-modality setting.
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Current Clinical Trials of Molecularly Targeted Agents in Children With Cancer, Part 2A number of molecularly targeted agents directed at critical cell survival and cell proliferation pathways have recently entered clinical evaluation in children with cancer. These agents offer the potential for more effective anticancer therapy while simultaneously diminishing acute and long-term toxic effects. Systematic evaluations of targeted agents are essential to achieving continued improvements in outcome for children with cancer. Brief summaries of the rationale for conducting studies of several agents in children are provided below. Following these summaries is a listing of phase I, phase I/II, phase II, and pilot studies of these and other agents in pediatric populations.
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Provocative Pearls in Diagnosing and Treating Acute Promyelocytic LeukemiaThe treatment of APL in the modern era is a success of modern hematology. In this review we have attempted to plant the seeds of understanding regarding how diagnosis and treatment of APL will be pursued over the next decade.
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Promising First-Line Therapeutic Approaches for Adult Patients With AMLEytan Stein, MD, considers promising, new therapeutic options for adult patients with acute myeloid leukemia.
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The Health Economics of Palliative CareOften, Congressional financing of programs can be secured only with indirect arguments. In the 1950s, the Eisenhower administration convinced Congress to fund the interstate highway system by claiming it was essential to enable Americans to evacuate cities in case of a nuclear attack by the Soviet Union. In the 1970s, advocates trying to persuade Congress to pay for dialysis argued that the procedure would be inexpensive, and that people would return to work and pay for themselves. Similarly, in the early 1980s, proponents of hospice advocated Medicare coverage because it was cheaper and better care for the dying.
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Commentary (Cohen/Vokes): Gene Therapy for Head and Neck CancersThis issue of Oncology features an excellent review of gene therapy for head and neck cancers. Lamont and colleagues have highlighted the principles of genetic intervention, the current state of available therapies, and the results of human trials in an organized and coherent manner.
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The Impact of Molecular Testing on Treatment of Cancer of Unknown Primary OriginThe preponderance of data support the accuracy of molecular assay diagnoses in about 80% to 90% of patients with known advanced primary cancers and in patients with cancer of unknown primary origin.
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Efficiency of In Vivo Purging With Rituximab Followed by High-Dose Therapy With Autologous Peripheral Blood Stem Cell Transplantation in B-Cell Non-Hodgkin’s Lymphomas: A Single-Institution StudyHigh-dose therapy (HDT) with peripheral blood stem cell transplantation is a treatment option for patients with advanced follicular, marginal, and mantle cell lymphoma. In this setting, frequent contamination of peripheral blood stem cell harvests by
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Radiotherapy Versis Chemotherapy as ConsolidativeTreatment for Stage IIIB-IV Hodgkin’s Disease in First Complete Remission or Good Partial Response: A Study of 559 Patients (H89 Protocol)The role of radiotherapy in combination with chemotherapy in advanced-stage Hodgkin’s disease remains controversial.
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2 Cycles of ABVD Plus Radiotherapy Is More Effective Than Radiotherapy Alone in Early Stage HD-Interim Ahan Radiotherapy Alone in Early Stage HD-Interim Analysis of the HD7 Trial of the GHSG Clinic of Internal Medicine I University of Cologne/GermanyBACKGROUND: Extended-field radiotherapy is effective in patients with early-stage Hodgkin’s disease, and more than
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Thyroid and Parathyroid CancersThis management guide of endocrine malignancies covers the risk factors, diagnosis, screening, and treatment of both thyroid and parathyroid cancers.
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Hematopoietic Stem Cell Transplantation for Non-Hodgkin’s LymphomaHigh-dose myeloablative therapy with autologous or allogeneicstem cell rescue is an effective treatment strategy for non-Hodgkin’slymphoma (NHL), but NHL is much less likely to stay in remission afteran autologous transplant than after an allogeneic transplant. Thebenefit of undergoing an autologous transplant earlier in the course ofthe disease, especially for patients who present with intermediate orhigh scores on the International Prognostic Index of risk factors, is stillunclear. The addition of immunotherapy, biologic modifiers, andantibody therapy such as rituximab (Rituxan) or radiolabeled antibodyto the autologous transplant are approaches undergoing evaluation.Historically, there has been a high regimen-related mortality rateassociated with myeloablative allogeneic transplant that has made thisapproach a less appealing option for therapy. The use of nonmyeloablativeallogeneic transplants as treatment for NHL is less well studiedand remains to be defined.
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Neuraxial Infusion in the Management of Cancer PainPain due to malignancy can be controlled through simple means in most patients. In certain refractory cases, however, the chronic delivery of analgesics to the epidural or subarachnoid space may be appropriate. This review
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Activity of Rituximab in Extranodal Marginal Zone Lymphomas (MALT Type)This phase II study aimed to evaluate the tolerability and activity of the monoclonal anti-CD20 antibody rituximab (Rituxan) in patients with either untreated or relapsed biopsy-proven extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type, with measurable or evaluable disease.
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Relapsed Follicular Lymphoma: Response to a Fludarabine/Mitoxantrone Regimen and the Monoclonal Anti-CD20 Antibody RituximabOur objective was to determine the efficacy of a fludarabine (Fludara)/mitoxantrone (Novantrone) regimen combined with the monoclonal anti-CD20 antibody rituximab (Rituxan) to induce clinical and molecular remissions in patients with relapsed
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Relapsed Follicular Lymphoma: Response to a Fludarabine/Mitoxantrone Regimen and the Monoclonal Anti-CD20 Antibody RituximabOur objective was to determine the efficacy of a fludarabine (Fludara)/mitoxantrone (Novantrone) regimen combined with the monoclonal anti-CD20 antibody rituximab (Rituxan) to induce clinical and molecular remissions in patients with relapsed
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Treatment for Advanced Melanoma: New Drugs, New Opportunities, New ChallengesRemarkably, within 2 years of the introduction of ipilimumab and vemurafenib into the clinic, major new advances have been reported in both the immune checkpoint blockade and small-molecule kinase inhibition arenas.
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Encouraging Improvement in Cytopenias of Patients With Myelodysplastic Syndromes With ThalidomideMyelodysplastic syndrome patients present with variable cytopenias even though their bone marrows are generally hypercellular. Excessive cytokine-induced apoptosis of hematopoietic cells in the marrows has been proposed as a possible
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Immunotherapeutic Approaches Have the Potential to Brighten the Future Not Only for Patients With del(17p13.1), but for All CLL PatientsMost cases the clinical management of CLL patients with del(17p13.1) poses enormous challenges, and patients should be included in clinical trials whenever possible. However, there are a number of promising novel drugs and immunotherapy strategies under investigation.
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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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Alternatives to Oral Opioids for Cancer PainAlthough the optimal route of administration of opioids is by mouth, some patients may require alternative routes during the course of their illnesses for several reasons. These include bowel obstruction, severe emesis, or severe
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How to Address Sexual Problems in Female Cancer PatientsSexual health is an important aspect of human life, and cancer does not (and should not) change that. Data suggest that issues related to sexual function are quite common among women treated for cancer. However, clinicians often spend little to no time on the topic.
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Commentary (Giaccone/Barlesi): Perspectives on Salvage Therapy for Non–Small-Cell Lung CancerCappuzzo and colleagues havereviewed the present optionsof salvage therapy for advancednon–small-cell lung cancer(NSCLC). This issue is highly relevantnowadays, as many patients whofail palliative chemotherapy are stillin sufficiently good condition to receiveadditional therapy. It is ratherinstructive to note that 10 years agothe use of systemic chemotherapy foradvanced NSCLC was advocated butstill not standard, and today we haveseveral options for treating patients inthe second- and even third-line setting.Among these options are agents thatspecifically target molecular featuresof lung cancer, such as the epidermalgrowth factor receptor (EGFR)
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Colorectal Cancer Surgical Practice GuidelinesThe Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in
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Lymphatic Mapping in the Treatment of Breast CancerDeveloped initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested
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Commentary (Tahn/Khuri): Second-Line Treatment of Small-Cell Lung CancerSmall-cell lung cancer (SCLC)poses one of the greatest managementchallenges in clinicaloncology, as the mortality rate approaches95% within 2 years afterpresentation for patients with extensivedisease, despite widespread useof combination chemotherapy.[1]Given a disease that is largely managedby the community physician andfor which recent definitive clinicaltrials are relatively scarce,[2] it isincumbent upon the clinician to becognizant of the critical factors innostudies suggesting that three-drugcombinations are indicated.
