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Empiric Antifungal Therapy for the Neutropenic PatientThe article written by Drs. Wingard and Leather presents a thoughtful review of the current approaches to empiric antifungal therapy in neutropenic patients. Empiric antifungal therapy has evolved as a standard of care for the prevention of invasive fungal infections in neutropenic patients who remain persistently febrile despite the use of broad-spectrum antibacterial antibiotics.[1-3] Empiric antifungal therapy in this setting provides early treatment for clinically occult invasive fungal infections and systemic prophylaxis for neutropenic patients at highest risk.
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State-of-the-Art Treatment for Advanced NonSMQ-8211-SMQSmall-Cell Lung CancerPatients with locally advanced or metastatic nonSMQ-8211-SMQsmall-cell lungcancer (stage III and IV) who are not candidates for surgery and exhibitgood performance status are typically treated with concurrent radiationand platinum-based chemotherapy for disease palliation. Platinum-based chemotherapies, used alone or with radiation therapy, offera small but significant survival benefit compared with supportivecare. The incorporation of first-line agents such as gemcitabine(Gemzar), vinorelbine (Navelbine), and paclitaxel, as well as secondlineagents such as docetaxel (Taxotere), in doublet and triplet combinationshas had a further significant therapeutic impact. Randomizedtrials have shown that cisplatin-based therapy in combination with newagents results in improved 1- and 2-year survival rates in patients withadequate performance status. The 1-year survival benefit has significantlyimproved, with greater symptom relief and improved quality oflife in these patients. Thus, delaying disease progression with combinationchemotherapy appears both beneficial and cost-effective in patientswith advanced nonSMQ-8211-SMQsmall-cell lung cancer. Newer approachesSMQ-8212-SMQincluding targeting critical signaling pathways, such as tyrosine kinasereceptors, angiogenesis, and downstream signal transductionmechanismsSMQ-8212-SMQmay provide novel agents with an improved toxicity profileand the potential for better disease management.
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Depression, anxiety, and deliriumAlthough many cancer patients cope well with their disease, psychiatric disorders occur in almost 50% of patients in the setting of malignancy. Untreated psychological and neuropsychiatric disorders can compromise quality of life as well as treatment compliance. Three behavioral syndromes that are often encountered in clinical practice will be discussed here: depression, anxiety, and delirium.
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Prostate-Specific Antigen as a Marker of Disease Activity in Prostate Cancer: Part 2Despite the impact of prostate-specific antigen (PSA) testing on the detection and management of prostate cancer, controversy about its usefulness as a marker of disease activity continues. This review, based on a
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Cancer Management Chapter 21: Bone sarcomasBone sarcomas are extremely rare neoplasms, which precludes determination of their true incidence. In 2009, approximately 2,570 new cases of cancer of the bones and joints will be diagnosed in the United States, and some 1,470 patients will succumb to the disease. Population-based tumor registries seldom separate bone sarcomas into various histologic types.
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Adult Medulloblastoma, From Spongioblastoma Cerebelli to the Present Day: A Review of Treatment and the Integration of Molecular MarkersHere we present the history, staging system, and treatment of medulloblastoma, reviewing the prognostic value and clinical application of molecular subtyping while highlighting the differences between adult and pediatric disease.
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UFT Plus or Minus Calcium Folinate for Metastatic Colorectal Cancer in Older PatientsTwo studies were carried out to determine the activity and evaluate the toxicity of oral chemotherapy with uracil and tegafur in a 4:1 molar ratio (UFT) plus or minus calcium folinate in elderly patients with advanced colorectal
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An Overview of Adenocarcinoma of the Small IntestineOf all the digestive tract tumors, small-bowel cancers are the least common. Why should we study these rare tumors, and what, if anything, can we learn from them? Sometimes the absence of an important event can provide the answer to a difficult problem. For example, consider the famous Sherlock Holmes mystery story, "Silver Blaze," in which the master sleuth solved a challenging case, simply because the watchdog didn't bark when he should have, implying that the murderer was well known to the dog.[1]
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Nonoperative Management of Rectal Cancer: A Modern PerspectiveIn this article, we provide a summary of nonoperative management of locally advanced rectal cancer in the modern era. Our focus is on technical details of tumor response and patient assessment after chemoradiotherapy, as well as a review of existing clinical data.
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Recent Progress in Radioimmunotherapy for CancerRadioimmunotherapy allows for the delivery of systemically targeted radiation to areas of disease while relatively sparing normal tissues. Despite numerous challenges, considerable progress has been made in the application of radioimmunotherapy to a wide variety of human malignancies. The greatest successes have occurred in the treatment of hematologic malignancies. Radioimmunotherapy, with or without stem-cell transplant support, has produced substantial complete remission rates in chemotherapy-resistant B-cell lymphomas. Nonmyeloablative regimens have shown so much promise that they are now being tested as initial therapy for low-grade B-cell lymphomas. Although solid tumor malignancies have been less responsive to radioimmunotherapy, encouraging results have been obtained with locoregional routes of administration, especially when the tumor burden is small. Greater tumor-to-normal tissue ratios are achievable with regional administration. Even with intraperitoneal and intrathecal administration, bone marrow suppression remains the dose-limiting toxicity. Ongoing research into new targeting molecules, improved chelation chemistry, and novel isotope utilization is likely to extend the applications of this strategy to other tumor types. The potential for radioimmunotherapy will be enhanced if this modality can be optimally adapted for integration with other agents and if the administration method can be tailored to the type and distribution of malignancy. [ONCOLOGY 11(7):979-987, 1997]
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Radium-223: Down to the Bone, and Less Is MoreRadium-223 is a promising agent that represents a new class of alpha pharmaceuticals that gets down to the site of bony metastases. The limited side-effect profile potentially allows for repeat administration to increase durability of pain control, and for its use in combination with novel biologic and chemotherapeutic agents.
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Current Techniques in Three-Dimensional CT Simulation and Radiation Treatment PlanningThe modern CT simulator is capable of interactive three-dimensional (3D) volumetric treatment planning; this allows radiation oncology departments to operate without conventional x-ray simulators. Treatment planning is performed at the time of virtual simulation by contouring the organs or volumes of interest and determining the isocenter.
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Propelling Immunotherapy Combinations Into the ClinicThis review summarizes promising new targets and immunotherapy combination strategies currently under clinical development.
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Node-Positive Prostate Cancer: A Call for Level 1 EvidenceDespite the lack of level 1 evidence, retrospective studies support the need for appropriate local treatment, even in the context of node-positive disease.
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Commentary (Selman/Copeland): Management of Intestinal Obstruction in the Patient With Ovarian CancerAuthors Thomas Randall, MD, and Stephen Rubin, MD, provide a thoughtful, state-of-the-art discussion on current controversies in the management of intestinal obstruction in patients with ovarian cancer.
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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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Doxorubicin and Paclitaxel (Sequential Combination) in the TreatmentBased on preclinical data, we designed a phase I/II clinical trial to determine the efficacy and toxicity of doxorubicin followed by paclitaxel in the treatment of advanced breast cancer (either untreated or relapsed after
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Multidisciplinary Management of Pediatric Soft-Tissue SarcomaThe management of pediatric soft-tissue sarcomas has improved drastically through the use of multimodal therapy. These tumors include rhabdomyosarcomas and nonrhabdomyosarcomas. Both are staged using
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Pemetrexed in Gastric CancerGastric cancer is a major clinical challenge, with poor overall prognosisand limited life expectancy for patients with advanced disease.Even with surgery and other modalities, palliation is often difficult.Improvement of response rates has evolved with the development ofstandard regimens and those incorporating newer chemotherapy agents,such as oral fluoropyrimidines, the taxanes, camptothecins, novel platinums(eg, oxaliplatin [Eloxatin]), and antifolates (eg, pemetrexed[Alimta]). Ongoing trials with these regimens aim toward improvingsurvival, as well as improving the safety profile. It is hoped that in conjunctionwith molecular research in the pathogenesis of gastric cancerand development of targeted therapies in this disease, these trial datamight lead to the evolution of treatment strategies that could prove effective.
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Gemcitabine/Paclitaxel as First-Line Treatment of Advanced Breast CancerGemcitabine (Gemzar) and paclitaxel exhibit good activity and goodsafety profiles when used alone and together in the treatment of advancedbreast cancer. In a phase II trial, 45 patients with metastaticbreast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 andpaclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients(60.0%) had prior adjuvant therapy. Objective response was observedin 30 patients (objective response rate 66.7%, 95% confidence interval[CI] = 52%–71%), including complete response in 10 (22.2%) and partialresponse in 20 (44.4%). Median duration of response was 18 months(95% CI = 11–26.7 months), median time to tumor progression for theentire population was 11 months (95% CI = 7.1–18.7 months), medianoverall survival was 19 months (95% CI = 17.3–21.7 months), and the1-year survival rate was 69%. Treatment was well tolerated, with grade3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, andthrombocytopenia were each observed in six patients (13.3%). No patientwas discontinued from the study due to hematologic ornonhematologic toxicity. Thus, the gemcitabine/paclitaxel combinationshows promising activity and tolerability when used as first-line treatmentin advanced disease. The combination recently has been shownto be superior to paclitaxel alone as first-line treatment in anthracyclinepretreatedadvanced disease according to interim results of a phase IIItrial and it should be further evaluated in comparative trials in breastcancer.
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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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Acute Myeloid Leukemia in the Elderly: A Unique DiseaseAcute myeloid leukemia (AML) is a disease of the elderly, with the majority of patients diagnosed in their 6th and 7th decade of life. Older patients with AML are less likely to achieve complete remission after induction chemotherapy, and they suffer from higher rates of leukemia relapse compared to younger cohorts. Suboptimal outcomes are the result of adverse biologic characteristics of leukemia in the elderly, as well as the presence of medical comorbidities and patient or physician preferences as to initiating treatment. In addition, there is a distinct lack of randomized, prospective data to guide management decisions for the treatment of AML in the elderly. Patients who are over age 75, with poor performance status, multiple comorbidities, or poor prognostic features, should be considered for a clinical trial or palliative therapy. Elderly patients who are candidates for standard induction chemotherapy and achieve complete remission are unlikely to benefit from intensive postremission therapy and should be referred to a clinical trial when possible. Further prospective trials are needed to identify a tolerable, effective treatment regimen for older patients with AML.
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New Combinations With Epirubicin in Advanced Breast CancerSeveral trials have shown that anthracyclines and taxanes can be combined to achieve response rates ranging from 70% to 90%, with complete responses ranging from 19% to 41%. In an attempt to increase the activity while
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The Diagnosis and Management of Retroperitoneal SarcomaRetroperitoneal sarcoma is a rare tumor whose diagnosis and management can be challenging and for which management requires a multidisciplinary team.
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Gemcitabine and Pemetrexed Disodium in Treating Breast CancerPemetrexed disodium (Alimta, LY231514) is a novel, multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. This agent is broadly active in a wide
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Mutation-Derived Tumor Antigens: Novel Targets in Cancer ImmunotherapyBecause of the abundance of promising preclinical and early-phase clinical data, mutation-derived tumor antigens an exciting new class of targets in cancer immunotherapy.
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Recent Advances With Chemotherapy for NSCLC: The ECOG ExperienceManagement of disseminated non-small-cell lung cancer has changed over the past 10 years. Newer agents, such as vinorelbine (Navelbine) and paclitaxel (Taxol), have been shown to modestly improve survival in patients with
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Synopsis of Angiogenesis Inhibitors in OncologyAngiogenesis is a dynamic process essential for primary tumor growth and metastases. New insights into the basic understanding of the biologic processes responsible for angiogenesis have led to the characterization of potential therapeutic targets. Several strategies for the development of antiangiogenic therapeutic modalities have been employed, including agents that (1) decrease the activity of specific angiogenic factors, (2) decrease the activity of endothelial survival factors, (3) increase the activity of naturally occurring antiangiogenic agents, or (4) indirectly downregulate angiogenic and survival factor activity.
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Pegylated Liposomal Doxorubicin: Antitumor Activity in Epithelial Ovarian Cancer or Cancers of Peritoneal OriginAfter pegylated liposomal doxorubicin (PEG-LD) (Doxil) was shown to be active in ovarian tumors, several trials were developed at the University of Southern California to determine its safety and efficacy in a variety of gynecologic and peritoneal malignancies. Completed phase I and phase II trials have found PEG-LD to be safe and effective in the treatment of platinum- and paclitaxel-refractory epithelial ovarian carcinoma. A new phase II trial is currently underway in similarly refractory patients with ovarian and other related cancers and various degrees of pretreatment. In addition, the efficacy of PEG-LD is being explored in combination with paclitaxel (Taxol), with cisplatin, and with hyperthermia. [ONCOLOGY 11(Suppl 11):38-44, 1997]
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Update on Newer Non–EGFR-Targeted Agents in Non–Small-Cell Lung CancerMSKCC’s Dr. Alexander Drilon highlights other known alterations that are being targeted or being used as biomarkers in non–small-cell lung cancer.
