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An Extended Time Frame for VTE Risk in Bladder CancerCancer promotes the development of venous thromboembolism (VTE) by inducing a hypercoaguable state, through mechanisms that are complex and multifactorial.
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Transplant Registries: Guiding Clinical Decisions and Improving OutcomesAbout 50,000 hematopoietic stem cell transplantations are performed yearly, primarily for malignancies. Use of this therapy increased dramatically over the past 30 years due to its proven and potential efficacy in diverse
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Fay Hlubocky on Recognizing and Addressing Clinician BurnoutIn this interview we discuss the issue of burnout in oncology, including signs and risk factors, how it might affect patient care, and strategies for prevention.
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Docetaxel/Doxorubicin/Cyclophosphamide in the Treatment of Metastic Breast CancerA pilot phase II study examined the feasibility of 75 mg/m² of docetaxel (Taxotere) in combination with 50 mg/m²of doxorubicin and 500 mg/m² of cyclophosphamide (Cytoxan, Neosar) in the first-line treatment of metastatic breast cancer. This study was designed to evaluate the efficacy and toxicity of the docetaxel/doxorubicin/cyclophosphamide combination both alone and as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation.
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Commentary (Corica/Keane): Organ Preservation in Muscle-Invasive Bladder CancerThis is a timely review on thecurrent status of selective bladderpreservation for muscleinvasivebladder cancer. Although controversial,the concept is extremely attractiveto patients, and evidence fromretrospective and/or small series demonstrateits efficacy. Most of these trials,however, have included highlyselected patients. Unfortunately, thereare few, if any, ongoing randomizedcontrolled trials comparing radical cystectomyto bladder-preserving protocols.Although the overall 5-yearsurvival rate for radical cystectomy andtrimodality therapy is approximately50%, patients with pure T2 disease frequentlyachieve 5-year survival ratesapproaching 70%.[1-3] While it is clearlybeyond the scope of this editorial togo into an in-depth analysis of all thestudies reported to date, several significantquestions remain.
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What Is the Indication for Sorafenib in Hepatocellular Carcinoma? A Clinical ChallengeIn this review article we will discuss the current data on, and future role of, sorafenib in the treatment of hepatocellular carcinoma beyond Child-Pugh A cirrhosis, in conjunction with local therapy, and in a transplant setting.
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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.
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Uracil/Tegafur Plus Oral Calcium Folinate in Advanced Breast CancerUracil and tegafur (in a molar ratio of 4:1 [UFT]) has proven activity against breast cancer and is delivered in an easy-to-administer oral formulation. Orzel, which combines UFT with the oral biomodulator, calcium folinate, may
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Bone marrow procedures move into the 21st centuryMore than 700,000 biopsies are performed in the U.S. every year, but the technology has not always kept pace with cancer diagnosis and therapy. A new technique allows rapid and easy access to the marrow space.
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Best Treatment of Aggressive Non-Hodgkin’s Lymphoma: A French PerspectiveThe Groupe d’Etude des Lymphomes de l’Adulte (GELA) has conductedseveral phase II and III studies in patients with aggressive lymphoma,diffuse large B-cell lymphoma (DLBCL), and T-cell lymphomasduring the past 20 years, in France and Belgium. These studieshave demonstrated that the outcome of patients with DLBCL may beimproved and that the standard CHOP (cyclophosphamide, doxorubicinHCl, vincristine [Oncovin], prednisone) regimen is not sufficient tocure a large number of patients. The first improvement was the demonstrationof superiority of a dose-dense and dose-intense regimen, ACVBP(doxorubicin [Adriamycin], cyclophosphamide, vindesine, bleomycin,prednisone). The second improvement was made in young patients withpoor-risk lymphoma by intensifying their treatment with high-dosetherapy and autotransplant. The third and most significant improvementwas in the results associated with the combination of rituximab(Rituxan) and chemotherapy. Current studies look at decreasing thenumber of patients truly refractory to chemotherapy, decreasing relapserate with rituximab maintenance, and finding an appropriate regimenfor patients with T-cell lymphoma.
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Emerging Categories of Disease in Advanced Prostate Cancer and Their Therapeutic ImplicationsIn this article, we look at both metastatic hormone-sensitive and metastatic castration-resistant disease, and we highlight several of the emerging categories of advanced prostate cancer that have direct implications for patient management.
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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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Commentary (Cabanillas)-Follicular Lymphoma: Expanding Therapeutic OptionsIn their manuscript, Ganti et al tackle a very intricate and controversial subject: follicular non-Hodgkin’s lymphoma (NHL). The manuscript attempts to exhaustively cover multiple aspects of the disease, including pathology, prognostic factors, natural history, treatment of early-stage as well as advanced disease, relapsed disease, newer agents, monoclonal antibodies, interferon, radioimmunotherapy, stem cell transplantation, and future directions. To review all these topics thoroughly would almost require a textbook. To meticulously cover all of these aspects in a review article is a nearly impossible task. From my standpoint as a reviewer, to critique this article is an equally complicated task. I will therefore focus on only a few major issues.
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Extended Transbasal Approach to Skull Base TumorsA variety of novel surgical approaches have been developed in recentyears to manage disease of the cranial base. Few offer the widthand depth of exposure achievable with the extended transbasal approach.This approach combines a bifrontal craniotomy with anorbitonasal or orbitonasoethmoidal osteotomy, and potentially asphenoethmoidotomy to provide broad access to malignancies of theanterior, middle, and posterior skull base. The approach enables the enbloc resection of tumors within the frontal lobes, orbits, paranasal sinuses,and sphenoclival corridors without brain retraction and mayobviate the need for transfacial access. This can be combined with additionalapproaches, based on the tumor's epicenter. Reconstruction isaccomplished with the use of pericranium, and in some instances, atemporalis muscle pedicle or a gracilis microvascular free flap. Complicationsinclude cerebral spinal fluid leakage, pneumocephalus, infection,and cranial neuropathies. However, the morbidity and mortalityassociated with this approach is low. The extended transbasal approachis a relatively novel exposure that enables the skilled cranialbase surgeon to safely excise many malignant lesions previously felt tobe unresectable.
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Renal Cancer Management in a Patient With Chronic Kidney DiseaseA 69-year-old man presented in the urology clinic for evaluation of bilateral renal masses, discovered incidentally during routine exams for follow-up of his chronic kidney disease.
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A Phase II Study of Doxorubicin/Paclitaxel Plus G-CSF for Metastatic Breast CancerThis phase II trial was conducted to evaluate the percentage of objective responses and the toxicity profile of combination doxorubicin (Adriamycin) and paclitaxel (Taxol) with granulocyte colony-stimulating factor as first-line
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Pemetrexed in Second-Line Treatment of Non–Small-Cell Lung CancerAccording to the updated 2004 guidelines of the American Societyof Clinical Oncology (ASCO) on the treatment of advanced non–smallcelllung cancer (NSCLC), docetaxel (Taxotere) can be considered thestandard second-line chemotherapy in patients relapsing after frontlinetherapy. This was based on two phase III trials (TAX 317 and TAX320) that demonstrated the superiority of docetaxel at 75 mg/m2 in theparameters of survival, quality of life, and disease/symptom controlwhen compared to best supportive care or alternative single-agent chemotherapy.The response rate was approximately 6%, with a mediansurvival time of 7 months and a 1-year survival rate of 30%. Despitethe activity demonstrated, this schedule showed an important toxicityprofile, with grade 3/4 neutropenia and febrile neutropenia occurringin 70% and 11% of patients, respectively. However, the results obtainedby these studies stimulated research interest in new drugs for this diseasesetting. Pemetrexed (Alimta), a new multitargeted antifolate, hasachieved promising results in NSCLC treatment, as a single agent or incombination with other drugs. In the second-line setting, a large phaseII study demonstrated good activity of pemetrexed, with an acceptabletoxicity profile. This led to a phase III registration trial that comparedpemetrexed at 500 mg/m2 to the standard docetaxel dose of 75 mg/m2.While results from this trial demonstrated a similar efficacy of the tworegimens in response rate and survival, pemetrexed achieved a bettersafety profile. These results support the use of pemetrexed as a newoption in the second-line treatment of NSCLC.
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The Benefits of Achieving Stable Disease in Advanced Lung CancerDr. Karen Kelly has written atimely discussion on the clinicalbenefit of achieving stabledisease in advanced non–smallcelllung cancer (NSCLC). The goalsof current therapy are to palliate symptoms,optimize quality of life (QOL),and prolong survival. It is argued thattumor shrinkage may not be mandatoryto achieve these goals, particularlyin the evaluation of moleculartargeted therapies that may be cytostaticrather than cytotoxic in theirmechanism of action. However, stabledisease is not regarded as evidenceof therapeutic efficacy byregulatory authorities. Furthermore, ifbased on radiologic measurements Continued on page 968.alone, this designation encompasses aheterogeneous population that includespatients who demonstrate unequivocaltumor shrinkage as well asmany with tumor growth. Therefore,the case is presented to define stabledisease in terms of clinical benefit byincorporating alternative trial endpoints such as symptom control, QOL,or biologic end points.
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Commentary (Sahebi/Forman): The Role of Hematopoietic Stem Cell Transplantation in Myelodysplastic SyndromeDrs. Thompson and Luger have written a thoughtful and comprehensive review of the therapeutic options and issues facing physicians caring for patients with myelodysplastic syndrome (MDS). In our commentary, we would like to highlight and expand on several areas of their analysis.
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Nuclear Medicine Imaging in Breast Cancer: Current Strategies and Future DirectionsThe article “PET Scan in the Diagnosis and Management of Breast Cancer” by Jame Abraham and coworkers is a complete, updated review of the existing scientific literature about clinical indications for positron-emission tomography (PET) in this malignancy.
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Late Toxicity of Radiotherapy and Chemotherapy in Hodgkin LymphomaThis interview examines treatment-related cardiotoxicity and the risk of second malignancy in patients with Hodgkin lymphoma.
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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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Simultaneously Detected Bilateral Testicular Cancer of Different Histopathological OriginA 36-year-old male with a history of cryptorchidism of the right side, treated with orchidopexy at the age of 4, presented with bilateral testicular swelling. Investigations included laboratory workup, ultrasound of both testes, as well as CT-scan of the chest, abdomen, and pelvis. Initial treatment was bilateral orchiectomy.
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Dealing With Ethical Dilemmas in Oncological Communication Involving Issues of Culture and AutonomyBeginning with its provocative opening case vignette, Nathan Cherny's article provides an opportunity for us to reflect on and possibly redirect our own attitudes and habits regarding difficult ethical issues in communication with our patients and their families, especially in the setting of cultural and religious diversity.
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Anti-Angiogenesis Therapy in Gynecologic MalignanciesThe purpose of this paper is to provide a review of site-specific treatment options that involve the targeting of angiogenesis in gynecologic malignancies.
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Next gen EGFR targeting drug promising in NSCLCFinding an effective treatment for all the complex iterations of cancer is akin to chasing an outlaw through a treacherous mountain range, in the estimation of Louis M. Weiner, MD, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.
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Pregnancy After Breast Cancer: From Psychosocial Issues Through ConceptionWomen face numerous issues if they either contemplate childbearing or become pregnant after the diagnosis of breast cancer. Based on a search of the English medical literature from 1966 to 1997, we make the following
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Current Paradigms in First-Line Treatment of Non–Small-Cell Lung CancerStandard first-line chemotherapy for the majority of patients withadvanced non–small-cell lung cancer (NSCLC) consists of platinumbasedcombination regimens including one of the newer-generationagents, such as gemcitabine (Gemzar), a taxane, vinorelbine(Navelbine), or irinotecan (Camptosar). Several effective regimens areavailable, the choice of which will depend on treatment goals, individualpatient or disease factors, as well as physician preferences. Thispaper surveys randomized trials of many of the newer-generation chemotherapycombinations in patients with advanced NSCLC to examineseveral issues, such as which new-generation regimen to use, whethera platinum agent is needed, the optimal number of drugs in the combination,and treatment duration.
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Prostate Cancer in a Man With Multiple Previous Cancerspatient is a 67-year-old male with mild obstructive symptoms and an American Urology Association symptom score of 8.[1] He was noted to have a prostate-specific antigen (PSA) level of 3.2 ng/mL. Because this represented a significant increase in his PSA velocity (rate of change over time), he proceeded to have a biopsy, which was positive for prostate cancer. He has no other complaints and visits us for an opinion on the treatment of his prostate cancer.
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Anthracycline vs Nonanthracycline Adjuvant Therapy for Breast CancerThe treatment of breast cancer has progressed substantially overthe past 15 years. Data from randomized adjuvant trials have shownthat the risk of disease recurrence and death is significantly reducedwhen adjuvant chemotherapy and/or hormonal therapy is added to treatment.As new strategies are incorporated, one of the continued controversiesin patient management is whether adjuvant anthracyclinesshould be the preferred treatment for all patients. Data from randomizedand translational clinical trials have become available and arehelping to elucidate the proper role of anthracyclines, as well as their acuteand long-term toxicities. In most situations, an anthracycline is currentlypreferred, but other single and combination chemotherapies arecurrently under evaluation and appear promising for use in the adjuvantsetting. Continued breast cancer research using molecular markers(such as topoisomerase II–alpha and gene clusters) as predictors oftreatment response, could help individualize decisions regardingwhether to incorporate anthracyclines into adjuvant therapy regimens.
