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ACR Appropriateness Criteria® Nonsurgical Treatment for Locally Advanced Non–Small-Cell Lung Cancer: Good Performance Status/Definitive IntentThe treatment of inoperable stage III non–small-cell lung cancer (NSCLC) remains a challenge due to high rates of distant metastasis, local recurrence, and toxicity associated with definitive therapy.
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Oropharyngeal Mucositis in Cancer TherapyOropharyngeal mucositis is a common and treatment-limiting sideeffect of cancer therapy. Severe oral mucositis can lead to the need tointerrupt or discontinue cancer therapy and thus may have an impacton cure of the primary disease. Mucositis may also increase the risk oflocal and systemic infection and significantly affects quality of life andcost of care. Current care of patients with mucositis is essentially palliativeand includes appropriate oral hygiene, nonirritating diet andoral care products, topical palliative mouth rinses, topical anesthetics,and opioid analgesics. Systemic analgesics are the mainstay of painmanagement. Topical approaches to pain management are under investigation.The literature supports use of benzydamine for prophylaxisof mucositis caused by conventional fractionationated head andneck radiotherapy, and cryotherapy for short–half-life stomatoxic chemotherapy,such as bolus fluorouracil. Continuing studies are investigatingthe potential use of biologic response modifiers and growth factors,including topical and systemic delivery of epithelial growth factorsand agents. Progress in the prevention and management of mucositiswill improve quality of life, reduce cost of care, and facilitate completionof more intensive cancer chemotherapy and radiotherapy protocols. Inaddition, improved management of mucositis may allow implementationof cancer treatment protocols that are currently excessively mucotoxicbut may produce higher cure rates. Continuing research related to thepathogenesis and management of mucositis will undoubtedly lead to thedevelopment of potential interventions and improved patient care.
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Folate: Effects on Carcinogenesis and the Potential For Cancer ChemopreventionA provocative array of observations from both laboratory and clinical investigations indicates that alterations in folate status modulate the process of neoplastic transformation in selected epithelial tissues. Diminished folate
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Low-Risk and Very-Low-Risk Prostate Cancer: Is There a Role for Focal Therapy in the Era of Active Surveillance? No, Focal Therapy Provides a False Sense of Security and No Proven BenefitsOne should not advise a patient with low- or very-low-risk prostate cancer to undergo a focal ablation. The kindest and gentlest approach is to first do no harm.
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Psychological Outcomes Associated With Anemia-Related Fatigue in Cancer PatientsThis article examines the relationships between chemotherapy-induced anemia, fatigue, and psychological distress among anemic cancer patients with solid tumors.
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Commentary (Tepper/Kim): Are We Overtreating Some Patients With Rectal Cancer?Adjuvant therapy, almost bydefinition, overtreats patients.It is the holy grail of those ofus involved in adjuvant therapy to definethe patients who are going to failso that we can decrease the incidenceof tumor recurrence and avoid givingadditional therapy to patients who havebeen cured by their primary treatment.
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Commentary (Childers): Laparoscopy in Gynecologic MalignanciesDr. Chi very nicely reviews the history of operative laparoscopy in gynecologic oncology and covers most of the applications currently considered to be useful.
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Joel W. Neal, MD, PhD Discusses the Data on Cabozantinib and Atezolizumab Use in Advanced NSCLCIn terms of tumor control, treatment with cabozantinib and atezolizumab led to an overall response rate of 19% among patients with advanced non–small cell lung cancer, according to Joel W. Neal, MD, PhD.
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Topotecan in Combination With Cisplatin for the Treatment of Stage IVB, Recurrent, or Persistent Cervical CancerTopotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval.
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Darbepoetin Alfa: Impact on Treatment for Chemotherapy-Induced Anemia and Considerations in Special PopulationsOur objective was to evaluate the effects of darbepoetin alfa (Aranesp) on hemoglobin and transfusions in anemic patients with cancer undergoing chemotherapy, and the impact of age, sex, baseline hemoglobin, chemotherapy
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Commentary (Brandes/Brahmer): Perspectives on Salvage Therapy for Non–Small-Cell Lung CancerAbout 172,570 new cases ofnon–small-cell lung cancer(NSCLC) are expected to bediagnosed in 2005 in the United States,and almost as many will die of thedisease. Patients with effusions or metastaticdisease are candidates for combinationchemotherapy. The regimensof choice are platinum-based combinationchemotherapy schedules. Giventhat most patients will experience diseaseprogression despite their initialtreatment, they may be eligible for second-line chemotherapy, provided theyhave an acceptable performance status.
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Targeted Therapy in Rectal CancerEpidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.
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Nutritional Implications of Dental and Swallowing Issues in Head and Neck CancerTumors of the head and neck account for 4% of cancers in the United States. Both the disease process itself and side effects of cancer treatment, such as xerostomia, dysphagia, and malnutrition, compromise oral health,
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Improving the Early Detection of Prostate Cancer: A Balancing ActImproved early detection of prostate cancer would ideally involve a noninvasive test that allows clinicians to distinguish aggressive cancers from relatively indolent ones. This distinction is especially important given that relatively few men who undergo screening are destined to die of prostate cancer.
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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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Darbepoetin Alfa Controversies, From Dosage Issues to Safety Concerns: the Larger LessonOur paper, “Darbepoetin Alfa Administered Every 2 Weeks Alleviates Anemia in Cancer Patients Receiving Chemotherapy,” at the time of its publication almost a decade ago, was impactful and frequently cited.
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Clinical Development of Eniluracil: Current StatusEniluracil is a potent inactivator of dihydropyrimidine dehydrogenase (DPD), which is the first enzyme in the degradative pathway of systemically administered 5-fluorouracil (5-FU). Two completely oral regimens of eniluracil plus 5-FU are being evaluated in clinical trials: (1) a chronic schedule with both agents administered BID in a 10:1 ratio for 28 days of a 5-week course, and (2) a 5-day schedule of eniluracil once daily on days 1 through 7 and 5-FU once daily on days 2 through 6. The clinical development of eniluracil is being pursued in several tumor types, including colorectal cancer, breast cancer, and pancreatic cancer. Response rates achieved in a phase II study of the chronic schedule of oral eniluracil/5-FU in patients with colorectal cancer compare favorably with those obtained in trials of intravenous 5-FU and leucovorin, while results from other trials are awaited. Safety analysis for the 28-day schedule has revealed a low incidence of severe toxicities, particularly as compared with standard 5-FU regimens. [ONCOLOGY 12(Suppl 7):52-56, 1998]
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Combined-Modality Therapy for Bladder CancerRadical cystectomy remains standard management for patients with locally advanced T2 through T4, N0, M0 transitional cell carcinoma of the urinary bladder.
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Comparing Radical Prostatectomy and Brachytherapy for Localized Prostate CancerThere are two problems with thepaper by Quaranta et al, neitherof which can be overcomewith discussion or sophistry. The firstconcerns the criteria used to determinewhether a report would be includedin this analysis. Specifically,any series with a median follow-up ofonly 3 years was included if it alsomet the other inclusion criteria. Thisis simply inadequate, as there is greatconsensus that studies with 3-year follow-up miss many recurrences. Thesecond problem with the paper is thedefinition of recurrence. The AmericanSociety for Therapeutic Radiologyand Oncology (ASTRO) criteriaused by the authors has proven inferiorto using a cutoff of 0.2 ng/mL forprostate-specific antigen (PSA) nadirfollowing brachytherapy. The inaccuracyin using ASTRO criteria fordetermining cure by brachytherapy isparticularly pronounced in series withshort follow-up such as the 3-yearmedian follow-up criterion used inthis paper.
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Systemic Therapy of Metastatic Melanoma: On the Road to CureIn this article, we summarize the systemic therapies now available for melanoma, with a focus on the recently approved agents for cutaneous melanoma; discuss important considerations in selecting a treatment from the available options; and highlight some of the promising investigational approaches for this disease.
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Head and Neck TumorsThis management guide covers the risk factors, symptoms, diagnosis, staging, and treatment of head and neck cancers (including tumors of the oral cavity, oropharynx, hypopharynx, larynx, supraglottis, glottis, subglottis, and nasopharynx) using radiation, surgery, and medical treatment.
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Successful Treatment of Melanoma Metastatic to the Left Atrium Using External Beam Radiation TherapyThe successful treatment of a patient with primary nasal melanoma metastatic to the lung, pulmonary vein, and left atrium using radiation therapy is described. The patient was effectively treated with a conventional external beam radiation fractionation scheme (rather than a more commonly used hypofractioned regimen) that was utilized to minimize risk of arterial embolus of the tumor or rupture of a vessel wall. A post-treatment CT demonstrated a significant decrease in the caliber of the right pulmonary vein and tumor thrombus. The patient never developed cardiac valvular dysfunction or acute life-threatening massive embolism of tumor from the atrium. Unfortunately, the patient experienced clinical decline secondary to the massive progression of intra-abdominal disease and subsequently died from multiple liver metastases and liver failure. Numerous studies and this case report demonstrate that radiation therapy can be very effective in the treatment of malignant melanoma, especially when only small volumes of disease need to be treated and adequate total doses are used. Therefore, radiation therapy appears to play an important yet underutilized role in the treatment of metastatic melanomas.
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Multidisciplinary Evaluation and Treatment: Evolution to Standard Clinical PracticeCombined-modality therapy integrating chemotherapy with radiotherapy and/or surgery is playing an increasing role in the day-to-day management of a wide variety of solid tumors. No longer is this approach solely a clinical research tool. In fact, in
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High-Risk Prostate Cancer: The Rationale for BrachytherapyIn the realm of general oncology, patients who present with aggressive, poorly differentiated malignancies are usually at high risk for disseminated disease, and systemic therapy often supersedes local therapy in importance. It is not surprising, then, that a similar systemic approach to therapy is often considered for patients who present with high-risk prostate cancer. This recommendation is often supported by much of the surgical literature that cites discouraging outcomes in these patients when treated by radical prostatectomy alone.
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Chronic Lymphocytic Leukemia With del(17p13.1): A Distinct Clinical Subtype Requiring Novel Treatment ApproachesThis review will discuss the pathophysiology associated with the del(17p13.1) interphase cytogenetic abnormality, the current generally poor outcomes in affected patients, currently approved therapeutic agents, and new agents now undergoing investigation.
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Commentary (Kirkwood et al): Radiotherapy for Cutaneous Malignant Melanoma: Rationale and IndicationsThe rigorous assessment of thebenefits of radiotherapy formelanoma has been confoundedby superstition on one hand, andreligious fervor on the other. In thisissue, Ballo and Ang have reviewedthe use of radiotherapy for melanoma,focusing primarily on the controversialtopic of adjuvant postoperativeradiotherapy to the primary tumor bedand regional lymphatics.
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Most oncologists believe their career choice was a good one, survey findsOncologists remain largely satisfied with their career choice, with 85% expressing satisfaction and 82% of that group saying they would recommend their specialty to a medical student, according to a survey conducted by Epocrates, a provider of online clinical decision support tools for mobile and desktop devices.
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Survivin(g) Adult T-cell Leukemia/LymphomaIn this issue of ONCOLOGY, Tobinai reviews the management of human T-cell lymphotropic virus type 1 (HTLV-1)–associated adult T-cell leukemia/lymphoma (ATL). Although rare in the United States, an estimated 10 to 20 million people are infected with HTLV-1 worldwide and 2% to 5% will develop ATL.[1]
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Apoptosis Mechanisms: Implications for Cancer Drug DiscoveryDefects in the regulation of apoptosis (programmed cell death) makeimportant contributions to the pathogenesis and progression of mostcancers and leukemias. Apoptosis defects also figure prominently inresistance to chemotherapy, radiotherapy, hormonal therapy, andimmune-based treatments. Apoptosis is caused by activation ofintracellular proteases, known as caspases, that are responsible directlyor indirectly for the morphologic and biochemical events thatcharacterize the apoptotic cell. Numerous proteins that regulate thesecell death proteases have been discovered, including proteins belongingto the Bcl-2, inhibitor of apoptosis, caspase-associated recruitmentdomain, death domain, and death effector domain families. Thesecaspase-regulating proteins provide mechanisms for linkingenvironmental stimuli to cell death responses or to maintenance of cellsurvival. Alterations in the expression and function of several apoptosisregulatinggenes have been demonstrated in cancer, suggesting targetsfor drug discovery. Knowledge of the molecular details of apoptosisregulation and the three-dimensional structures of apoptosis proteinshas revealed new strategies for identifying small-molecule drugs thatmay yield more effective treatments for malignancies. Apoptosisregulatinggenes are also beginning to find utility as targets for antisenseoligonucleotides.
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Interesting Times in the Diagnosis and Treatment of CLLOne of the greatest challenges facing the physician caring for patients with chronic lymphocytic leukemia (CLL) is the heterogeneity of this disease. Over the past decade, there have been major advances in understanding the pathophysiology of CLL, and in the identification of biomarkers that are helpful to predict the clinical course for individual patients. Over the same period, the available therapeutic options have developed dramatically, exemplified by the introduction of combination therapy with purine analogs and monoclonal antibodies, resulting in significant opportunities to induce complete remission (CR) in CLL patients.
