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Emerging Role of EGFR-Targeted Therapies and Radiation in Head and Neck CancerThe treatment of head and neck cancer has been at the forefront ofnovel therapeutic paradigms. The introduction of drugs that interactwith selective biologic pathways in the cancer cell has generated considerableattention recently. A wide variety of new compounds that attemptto target growth-signaling pathways have been introduced intothe clinic. A majority of studies in the clinic have focused on epidermalgrowth factor receptor (EGFR) antagonists, but future studies will likelybuild upon or complement this strategy with agents that target angiogenicor cell-cycle pathways. EGFR activation promotes a multitude ofimportant signaling pathways associated with cancer development andprogression, and importantly, resistance to radiation. Since radiationtherapy plays an integral role in managing head and neck squamouscell cancer (HNSCC), inhibiting the EGFR pathway might improveour efforts at cancer cure. The challenge now is to understand whenthe application of these EGFR inhibitors is relevant to an individualpatient and how or when these drugs should be combined with radiationor chemotherapy. Are there molecular markers available to determinewho will respond to EGFR inhibitors and who should be treatedwith alternative approaches? What are the mechanisms behind intrinsicor acquired resistance to targeted agents, and how do we preventthis problem? We need to formulate integrated laboratory/clinicalresearch programs that address these important issues.
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A Care Model for the Future: the Oncology Medical HomeSurvival for cancer patients in the United States ranks among the highest in the world.[1] Despite the demonstrated success of the US cancer delivery system, government and private payers are forcing changes to the delivery of and payment model for oncology care.
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Docetaxel Plus Cisplatin: An Active Combination Regimen in Non-Small-Cell Lung CancerDocetaxel (Taxotere) isa semisynthetic taxoid that possesses significant activity as a single
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Neuropathic Cancer Pain: The Role of Adjuvant AnalgesicsNeuropathic pain may be defined as pain related to abnormal somatosensory processing in either the peripheral or central nervous system. This pathophysiologic label is typically applied when the painful symptom is associated
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Molecular Targeting in Cancer Therapy: Can We Fulfill the Promise?Work remains in the development of a clinically useful tumor classification system that includes molecular characterization of tumors, in our understanding of the implications of tumor heterogeneity, and in the development of more relevant and efficient clinical trials. Nonetheless, there is great excitement that a new era in the treatment of cancer is beginning.
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A Young Woman With Distant Recurrent Metastatic Primary Vaginal Carcinoma Salvaged With Radical RadiotherapyPrimary carcinoma of the vagina accounts for 1% to 3% of all gynecologic malignancies, with 70% of cases occurring in women over age 60.[1] Hematogenous dissemination is rare at diagnosis but is more common in patients with advanced, neglected lesions.
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Hematologic Cancers Break Down a ‘Checkpoint’: Targeting the PD-1/PD-L1 AxisWhile the results of the multitude of ongoing PD-1 blockade trials are eagerly awaited, it is clear that research involving the immunotherapy of blood cancers is moving swiftly through this first “checkpoint” at breakneck speed. It is sure to be a fascinating ride.
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The Use of Serum hCG as a Marker of Tumor Progression and of the Response of Metastatic Urothelial Cancer to Systemic ChemotherapyA 55-year-old woman with a history of metastatic melanoma in remission for 8 years presented to the emergency department with gross hematuria. A CT scan, ordered because the patient was in menopause, demonstrated a bladder tumor.
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Contemporary Management of Prostate Cancer With Lethal PotentialScreening for prostate cancer by determining serum prostate-specificantigen (PSA) levels has resulted in a stage migration such thatpatients with high-risk disease are more likely to be candidates for curativelocal therapy. By combining serum PSA, clinical stage, and biopsyinformation-both Gleason score and volume of tumor in the biopsycores-specimen pathologic stage and patient biochemical disease-freesurvival can be estimated. This information can help patients and cliniciansunderstand the severity of disease and the need for multimodaltherapy, often in the context of a clinical trial. While the mainstays oftreatment for local disease control are radical prostatectomy and radiationtherapy, systemic therapy must be considered as well. A randomizedtrial has shown a survival benefit for radical prostatectomy inpatients with positive lymph nodes who undergo immediate adjuvantandrogen deprivation. Clinical trials are needed to clarify whether adjuvantradiation therapy after surgery confers a survival benefit. PSAis a sensitive marker for follow-up after local treatment and has proventhat conventional external-beam irradiation alone is inadequate treatmentfor high-risk disease. Fortunately, the technology of radiationdelivery has been dramatically improved with tools such as three-dimensionalconformal radiation, intensity-modulated radiation therapy,and high-dose-rate brachytherapy. The further contributions of pelvicirradiation and neoadjuvant, concurrent, and adjuvant androgen deprivationtherapy have been defined in clinical trials. Future managementof high-risk prostate cancer may be expanded by clinical trialsevaluating neoadjuvant and/or adjuvant chemotherapy in combinationwith androgen deprivation.
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Chemotherapy Dosing in the Setting of Liver DysfunctionAdvanced cancer in the setting of liver dysfunction poses a dilemmafor physicians, as many cancer chemotherapeutic agents undergo hepaticmetabolism. Most cytotoxic drugs have a narrow therapeutic index,and the administration of chemotherapy to patients with liver impairmentresults in complicated safety issues. We present a concise reviewof cancer chemotherapy dosing in the setting of liver dysfunction.Although caution in treating all patients with hepatic failure is essential,the use of certain agents provokes greater concern than others.Continuous-infusion fluorouracil, capecitabine (Xeloda), mechlorethamine(Mustargen), cyclophosphamide, topotecan (Hycamtin), andoxaliplatin (Eloxatin) appear to be relatively well tolerated. On thecontrary, taxanes, vinca alkaloids, irinotecan (Camptosar), andanthracyclines may cause unacceptable toxicity if administered to patientswith poor hepatic function. For many anticancer agents, the paucityof data prohibits formal dosing recommendations, and most guidelinesremain empiric.
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Tolerability and Side-Effect Profile of rhIL-11Safety data from two randomized phase II and one abbreviated phase III placebo-controlled, double-blind clinical studies in adult patients with nonmyeloid malignancies indicate that recombinant human interleukin-11 (rhIL-11, also known as oprelvekin [Neumega]) has an acceptable toxicity profile as therapy for the mitigation of chemotherapy-induced thrombocytopenia.
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Proposed Algorithm for Managing Ibrutinib-Related Atrial FibrillationAlthough ibrutinib-related atrial fibrillation (IRAF) occurs in up to 11% of patients in clinical trials, these studies have rarely fully characterized bleeding events or risk factors for bleeding when ibrutinib is combined with anticoagulation. Furthermore, guidelines do not provide direction regarding the preferred anti-arrhythmic agent for IRAF.
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Lung Cancer Screening: A New EraScreening is always an issue that generates a great deal of emotion, as recently seen with the controversies surrounding mammography and prostate-specific antigen (PSA) testing.
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Tamoxifen's Impact on the Management of Breast Cancer: The Oncologist's PerspectiveBreast cancer treatment has evolved greatly within the last 25 years. Tamoxifen was first introduced for the
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Clinical Trials in Ovarian Cancer, Part 2The American Cancer Society has estimated that 23,300 women will develop ovarian cancer in 2002, and 13,900 women will die from the disease.[1] The 5-year survival rate is about 80% for women with stage I disease, 50% for women with stage II disease, 25% for women with stage III disease, and 15% for women with stage IV disease. Among women with advanced-stage disease, optimal debulking surgery, as well as platinum/taxane-based adjuvant therapy prolongs disease-free and median survival.[2,3] Population-based data suggest that guidelines for therapy are not uniformly followed in community practice.[4] In addition, older patients appear to receive less aggressive treatment than younger patients.
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Commentary (Forman/Zaia): Vaccinations Against Infectious Diseases in Hematopoietic Stem Cell Transplant RecipientsWith the increasing successof both autologous and allogeneicmarrow transplantationin achieving cure of inheritedand acquired disorders, the numberof people who have become longtermsurvivors has steadily increasedworldwide. Concomitant with thisincrease has been greater attention tothe long-term health needs of theserecipients. Many studies have outlinedthe problems experienced bylong-term survivors and have betterinformed physicians about the medicalproblems that may require interventionand consultation.[1]
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Unfavorable, Complex, and Monosomal Karyotypes: The Most Challenging Forms of Acute Myeloid LeukemiaAlthough the overall prognosis for patients with acute myeloid leukemia (AML) associated with unfavorable, complex, or monosomal karyotypes is poor, some patients can be cured.
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Joleen Hubbard, MD, Highlights The “Exciting Space” Of Metastatic CRCNew studies and treatment options prove to be effective in treating metastatic CRC, notes Joleen Hubbard, MD.
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Individualizing Therapy for Metastatic Colorectal CancerDavies/Goldberg Article Reviewed. The past decade has seen exciting developments in the field of colorectal cancer, particularly in the setting of advanced disease.
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New and Newer Vascular Targets in OncologyThis 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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Cancer and Male Factor InfertilityWith the increasing success of multimodality anticancer therapy, most men of reproductive age will survive their malignancy. Reproductive function is a principal concern of these men. Health-care providers are shifting the
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Patterns of Chemotherapy Administration in Patients With Intermediate-Grade Non-Hodgkin’s LymphomaRecords from 653 patients treated between 1991 and 1998 in the Oncology Practice Patterns Study (OPPS) were analyzed to determine contemporary chemotherapy delivery patterns in patients with intermediate-grade non-
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Aromatase Inhibitor–Associated Musculoskeletal Symptoms: Etiology and Strategies for ManagementIn the United States, approximately 180,000 women are diagnosed with breast cancer annually.
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The Cost of Cancer Care: There Is More Than One Elephant in the RoomThe current system rations care in an irrational way. This irrational rationing is going to worsen, for the costs of the current system are simply not sustainable nor are they justifiable by almost any metric used.
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How Should We Care for Elderly Cancer Patients?The Hippocratic principle of not harming the patient has remained up to this day an undisputed dogma in medicine. It reminds the physician of the possible detrimental, if not lethal, outcome of the treatment he prescribes and implicitly enforces good medical practice, although the true impact will unlikely be known. Oncology is one subspecialty of Medicine where this dilemma-ie, the pros and cons of treatment-is continuously put to the test, as the physician must decide on treatment for an often life-threatening illness while taking into account individual factors such as the patient’s will, performance status, available standard treatment options, and possible experimental approaches.
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Management of Tumors of the Parapharyngeal SpaceBenign and malignant tumors can arise from any of the structures contained within the parapharyngeal space. Such tumors are very rare, however. Also, malignant tumors from adjacent areas (eg, the pharynx) can extend into the parapharyngeal space by direct growth, or distant tumors may metastasize to the lymphatics within the space. Although the history and physical examination can provide clues to the site of origin and nature of a parapharyngeal space tumor, imaging studies are more useful for defining the site of origin and extent of the mass, as well as its vascularity and relationship to the great vessels of the neck and other neurovascular structures. Surgery is the mainstay of treatment. The surgical approach chosen should facilitate complete tumor extirpation with minimal morbidity. Irradiation is administered as primary therapy in patients with unresectable tumors, poor surgical candidates, and selected other patients. Radiation therapy is also used after surgery for high-grade malignancies or when wide surgical margins cannot be achieved. [ONCOLOGY 11(5):633-640, 1997]
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The Promise of Cryotherapy in Prostate CancerThis is an expertly written summary of the experience with cryotherapy as primary treatment of prostate cancer and the rationale for proceeding toward more limited, organ-sparing approaches with this procedure as focal treatment for low-risk cancers. Growing evidence of overdetection and overtreatment in many men with low-risk tumors has resulted in the recognition that alternatives to conventional treatment strategies are needed. Observation, a laudable and appropriate approach, appeals to relatively few patients.
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Commentary (Ship): Management of Xerostomia Related to Radiotherapy for Head and Neck CancerIn 2005, an estimated 29,370 newcases of oral cavity and pharyngealcancers were diagnosed inthe United States, accounting for2.14% of all cancer cases.[1] Over7,000 individuals will die from thesecancers in this country in 2005-approximately one death per hour.Many advances have been made inthe diagnosis and treatment of thesecancers, yet the mortality rate remainshigh (5-year survival rate of ~50%).Probably the most important approachis early detection, since early-stagetumors are associated with markedlybetter survival rates than late-stagecancers that have already spread toregional tissues and lymphatics.
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Management of a Patient With Borderline Resectable Pancreatic CancerIn this case report, we discuss the presentation, workup, and therapeutic management of a 40-year-old man who presented with borderline resectable, periampullary pancreatic cancer and underwent a margin-negative resection following neoadjuvant chemoradiotherapy.
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Biomarkers, Pathology Help Target Breast Cancer TreatmentThe combination of biomarkers and molecular pathology will aid oncologists in developing targeted treatments for breast cancer, according to Samuel Aparicio, MD, PhD, who will be delivering a presentation on recognizing breast cancer heterogeneity in targeted treatment at the Miami Breast Cancer Conference this week.
