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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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Uncertainty in Medicine: A Talk With Dr. DjulbegovicIn part 2 of this interview, Benjamin Djulbegovic, MD, PhD, discusses the uncertainty principle in clinical trials. Dr. Djulbegovic is associate professor of medicine, Divisions of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa.
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Psychosocial Consequences of DNA Analysis for MEN Type 2Multiple endocrine neoplasia type 2 (MEN-2) is characterized by medullary thyroid carcinoma in combination with pheochromocytomas and, sometimes, parathyroid adenomas. Since 1993, the psychosocial implications of DNA analysis for MEN-2 have been studied in the Netherlands. This article summarizes the first results of that study. Individuals who applied for DNA analysis cited the need to reduce uncertainty as the major reason for wanting the test. An unfavorable test outcome resulted in anxiety and depression but also relief.
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Complications of Androgen Deprivation Therapy: Prevention and TreatmentThe myriad effects of androgendeprivation therapy (ADT) inmen were really not appreciateduntil those without metastatic prostatecancer received such treatment.For example, fatigue-now recognizedas a common toxicity of ADT-was once more likely attributed tometastatic disease. Today, however,patients who are otherwise fully functional,healthy, and asymptomatic arebeing treated for a rising prostate-specificantigen level after primary therapy.In these men, the side effects ofADT can be very dramatic and aremore clearly related to the initiationof therapy.
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Targeting the Androgen Receptor Signaling Axis to Reduce Testosterone Levels in Prostate Cancer: How Low Should We Go?It is now well established that castration-resistant disease can be effectively treated using newer androgen receptor-targeting agents such as abiraterone and enzalutamide.
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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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Surgical Treatment of Metastatic Pulmonary Soft-Tissue SarcomaThe lung is the most frequent site of metastasis from soft-tissue sarcomas. Due to the relative resistance of sarcoma to either chemotherapy or radiotherapy, compared to other solid tumors, surgical management of
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A 56-Year-Old Man with an Intranasal MassA 56-year-old man presents with an intranasal mass. What is your diagnosis?
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Obese Breast Cancer Patients and Survivors: Management ConsiderationsThis article will present feasible weight loss interventions, and will discuss practical implications of ongoing chemotherapy and endocrine therapy with regard to weight gain, and the impact of obesity on therapy-related conditions during breast cancer survivorship.
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Predicting Endocrine Therapy Responsiveness in Breast CancerThis article reviews ongoing progress in the effort to identify predictors of endocrine therapy responsiveness for breast cancer and discusses the value of “pre-treatment” vs “on-treatment” tumor profiling for predicting outcomes.
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Tumors of the Uterine CorpusCarcinoma of the endometrium is the most common female pelvic malignancy and the fourth most common cancer in females, after breast, bowel, and lung carcinomas. In 1995, an estimated 32,800 new cases of endometrial carcinoma and 5,900 related deaths will occur in the United States [1]. The relatively low mortality for this cancer is probably due to the fact that in 80% of cases, the disease is diagnosed when it is confined to the uterus.
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Biphenotypic Extramedullary Blast Crisis of Chronic Myeloid Leukemia With Variant Philadelphia Chromosome TranslocationA 45-year-old man with a known history of rheumatic fever and aortic valve replacement 15 years earlier presented with the chief complaint of a 1-month history of progressive, intense, nonmechanical lumbar pain.
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Induction Therapy for Early-Stage Non-Small-Cell Lung CancerData from adjuvant trials clearly indicate that one of the most importantproblems in patients with resected non-small-cell lung cancer(NSCLC) is compliance to chemotherapy. In the postoperative setting,significant comorbidities and incomplete recovery after surgery oftenmake it difficult for patients to tolerate or comply with systemic therapy.Therefore, it may be preferable to deliver chemotherapy before surgeryas "neoadjuvant" or "induction" chemotherapy. The rationale for usinginduction chemotherapy is based on evidence that chemotherapymight reduce tumor burden and possess activity againstmicrometastases, resulting in improved results by surgery, radiotherapy,or a combination. Moreover, induction therapy facilitates in vivo assessmentof tumor response or resistance. Potential drawbacks includethe risk of perioperative complications, and the possibility that the tumormass may become unresectable due to disease progression. Duringthe past decade, four phase III randomized trials evaluated the roleof induction chemotherapy in stage IIIA NSCLC. The first three studiesconsistently showed that induction chemotherapy improves survivalcompared with surgery alone. More recently, a large phase III trialperformed by French investigators suggested a survival benefit in stageI/II patients, but not stage IIIA. The high activity of new platinumbasedchemotherapy-based on response rate and 1-year survival inadvanced disease-reinforces the rationale for the use of these newcombinations in early-stage NSCLC, especially for a subset of patientstraditionally treated with surgery alone. Several phase III trials arecurrently evaluating the role of new doublets as induction chemotherapy;these are discussed in the article. The results of these ongoingphase III trials should help clarify the role of induction chemotherapyin early-stage disease.
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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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Unanswered Questions: Monoclonal Antibodies in the Treatment of Advanced Non–Small-Cell Lung CancerDespite the fact that bevacizumab and cetuximab are both in an advanced stage of clinical development for use in treatment for unresectable NSCLC (with bevacizumab already licensed for the use in clinical practice), several unanswered questions regarding these drugs remain. A number of ongoing trials have been specifically addressed to answer them, however, the first priority should be to personalize treatment, through clinical or biological markers, in order to better select patients who could benefit from targeted therapy with decreased toxicity.
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Modern Management of Recurrent Ovarian CarcinomaThe management of ovarian cancer entails a complex blend of medicaland surgical interventions. Managing patients with recurrent ovariancancer increases the complexity of therapies and adds palliative interventions.The presence of recurrent ovarian cancer is both emotionally andphysically taxing for patients as well as their caregivers. With an increasinglyinformed patient population, a balance must be achieved betweeneasily accessible information enabling patients to know that they nowhave an incurable disease and support for their hopes and desires to stillovercome their cancer. The decision tree in the management of recurrentovarian cancer blends many different factors. This discussion will separatethose factors as if they are pure elements. We will address managementbased on response to primary therapy and time to recurrence, thelocation of recurrence, symptoms of recurrence, the patient’s histopathology,and the patient’s primary stage as it relates to the extent of diseasepresent at the start of chemotherapy.
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Commentary (Ritenour): Sexual Health Issues in Men With CancerWhile the cancer patient may be affected by sexual dysfunction throughout the entire course of the disease, sexual health is largely underevaluated and undertreated. Sexual problems should be anticipated and patients should be actively screened as they are unlikely to initiate discussion on sexual issues.
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Diffuse Large B-Cell Non-Hodgkin Lymphoma in the Very Elderly: Challenges and SolutionsIn this review, we critically analyze clinical trials that were specifically designed for the very elderly, and we discuss the challenges encountered by investigators who are conducting studies in this patient population. We conclude by proposing an algorithm to help clinicians determine the optimal therapeutic strategy for treatment of DLBCL in very elderly patients.
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Integrated PET-CT: Evidence-Based Review of Oncology IndicationsPositron-emission tomography(PET)–computed tomography(CT) has added a new dimensionto the imaging of cancers andcombination PET-CT scanners are becomingincreasingly universal. Theuse of combination scanners has increasedrapidly over the past 2 years-industry estimates are that the majorityof PET units sold throughout the worldwill be combination PET-CT scanners-and the authors have providedtheir own clinical experience and areview of the literature. While there issubstantial literature on the clinicalutility of PET alone, the use of PETCTis relatively new. The authors suggestthere is incremental benefit tothe addition of structural information(ie, CT) obtained at the same time asthe functional PET imaging.
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Targeted Approaches to the Management of Follicular LymphomaThe treatment of follicular lymphoma has changed dramatically over the past several years. The availability of newer, novel forms of therapy has enabled the field to continue to evolve. In addition to having tumor-specific activity, these newer agents provide the possibility of a more favorable toxicity profile than conventional chemotherapy.
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Bone Marrow Biopsy for the Initial Staging of Patients With Lymphoma: Too Soon to Toss the TrephineAlthough the prospect is tempting, we do not believe there are sufficient grounds at this time to abandon bone marrow biopsy in patients with lymphoma. It still provides robust prognostic information, and in the majority of patients it remains an indispensable staging tool.
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Chemotherapy-Free Treatment of Follicular Lymphoma: We Have the Ingredients, Now for Some RecipesThe treatment of patients with follicular lymphoma is undergoing a substantial shift due to rapid development of highly effective agents targeting lymphoma-specific biologic processes and the tumor microenvironment.
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Synergizing Radiation Therapy and Immunotherapy for Curing Incurable CancersRadiation is often considered immunosuppressive, an activity that is most likely a result of the complex interplay of hormesis and the abscopal effect. The abscopal effect, also called the “distant bystander” effect, is a paradoxical effect of radiation on cellular systems whereby local radiation may have an antitumor effect on tumors distant from the site of radiation.
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Carboplatin/Gemcitabine Combination in Advanced NSCLCThe treatment of advanced non–small-cell lung cancer (NSCLC)has evolved rapidly over the past few years. Systemic chemotherapy isassociated with both quality of life and modest survival benefit for patientswith advanced NSCLC. Platinum-based doublet combinationsare the “standard of care.” The US Food and Drug Administration(FDA) has approved gemcitabine (Gemzar), a pyrimidine analog, to beused in combination with cisplatin for the treatment of advanced NSCLCin the first-line setting. Randomized clinical trials have established comparableefficacy with improved therapeutic index for the carboplatin/gemcitabine regimen when compared with cisplatin/gemcitabine andother platinum doublets. Nonhematologic toxicities occur at a lowerfrequency with carboplatin/gemcitabine combinations compared withother “standard” platinum-based doublets, whereas dose-limitingthrombocytopenia, the most common toxicity, rarely requires therapeuticintervention. Both the 3- and 4-week schedules of carboplatin/gemcitabine result in similar efficacy and toxicity profiles, but the3-week regimen is preferred. The combination of carboplatin andgemcitabine is an effective regimen with an acceptable toxicity profilefor the treatment of advanced NSCLC. This regimen can also be usedas a foundation for the development of innovative combinations withmolecularly targeted agents.
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Soft-Tissue SarcomasThe soft-tissue sarcomas are a group of rare but anatomically and histologically diverse neoplasms. This is due to the ubiquitous location of the soft tissues and the nearly three dozen recognized histologic subtypes of soft-tissue sarcomas.
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Commentary (Are/Abu-Rustum)-Laparoscopic Surgery for Cancer: Historical, Theoretical, and Technical ConsiderationsSurgery for cancer carries concerns of tumor dissemination related to tumor manipulation, tumor violation, and wound seeding. Minimally invasive surgery is now standard for several benign conditions, such as symptomatic cholelithiasis and surgical therapy of gastroesophageal reflux. With the minimally invasive surgery explosion of the 1990s, virtually every procedure traditionally performed via laparotomy has been performed successfully with laparoscopic methods, including pancreaticoduodenectomy for cancer. Shortly after the first descriptions of laparoscopic-assisted colectomy, reports of port-site tumor recurrences surfaced, raising concerns of using pneumoperitoneum-based surgery for malignancy. This review covers the development of laparoscopic surgery for cancer. Historical perspectives elucidate factors that helped shape the current state of the art. Theoretical concerns are discussed regarding surgery-induced immune suppression and its potential effects on tumor recurrence with both open and laparoscopic approaches. The concerns of laparoscopic port-site wound metastases are addressed, with a critical evaluation of the literature. Finally, a technical discussion of laparoscopic-assisted resections of hepatic and pancreatic tumors details patient selection, operative approach, and existing data for these operations.
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Locoregional Recurrence of an HPV-Positive Squamous Cell Carcinoma of the Head and NeckLocoregional recurrences are a major source of morbidity and mortality for patients with squamous cell carcinomas of the head and neck (HNSCC).
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Cisplatin/Paclitaxel vs Cisplatin/Teniposide for Advanced Non-Small-Cell Lung CancerA total of 332 patients with advanced non-small-cell lung cancer were randomized by the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative
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Youth Has No Age: Cancer Treatment for Older AmericansCalendar age and biological age do not always correspond. Pablo Picasso, source of the quote that begins the title of this commentary, lived a notoriously robust and active life through his later decades, dying in his nineties in the midst of a dinner party. In the oncology community, with the advent of targeted therapeutics and better supportive care, the disparity between the two is likely to be increasingly relevant to both research and practice. In this issue of ONCOLOGY, Chiappori et al review data supporting the idea that even in the context of standard cytotoxic chemotherapy, elderly patients with advanced NSCLC experience similar response rates and similar survival benefits to those seen in younger patients. They note that biases excluding elderly patients from clinical trials result in gaps in our knowledge of how to best treat older patients.
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Lung Cancer Management in 2010Exciting advances in understanding the biology of lung cancer have occurred over the last few years.
