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Race and Cancer Genetics: Lessons From BRCA1Health disparities among populations within the United States are well documented. In order to eliminate these disparities, we must further understand their sources. Are they the result of the unequal distribution of resources, racism, or inherent characteristics of ethnically or "racially" defined groups? How we define and discuss "race" has major scientific and moral consequences. In this issue, Leslie Klein Hoffman asks two major questions as they pertain to research on ethnic or "racially" defined groups. When is genetic research on a population appropriate? How should researchers define a given population? These questions are timely, and it is both humbling and instructive that the answers to these questions remain unclear.
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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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Navigating the Impact of Chemotherapy Shortages on Cancer Care and FinancesPharmaceutical, gynecologic oncology, and physician perspectives shed light on potentially mitigating the ongoing carboplatin and cisplatin shortages’ effects on cancer care in the United States.
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Radiation Therapy in the Management of Brain Metastases From Renal Cell CarcinomaBrain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.
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Risk of Breast and Ovarian Cancer in Women With Strong Family HistoriesAssessing the risk of breast and ovarian cancer starts with obtaining a complete and accurate family history. This can reveal evidence of inherited cancer risk. The highest risk of cancer is associated with germ-line abnormalities
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Commentary (Fuhrmann/Suter): Radiotherapy for Cutaneous Malignant Melanoma: Rationale and IndicationsIn their article on radiotherapy forcutaneous malignant melanoma,Drs. Ballo and Ang discuss fourkey points, which we will addressbelow.
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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 Utility of Molecular Testing in Colorectal Cancer: The Promise Needs ProgressMolecularly profiling colorectal cancer has opened many potential opportunities for the use of this information in therapeutic decision-making. However, at present, only RAS testing in the metastatic setting has a definitive place in the decision-making paradigm.
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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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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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Monitoring Residual Disease in Colon CancerDr. Luis Diaz spoke with Cancer Network about monitoring for residual disease in colon cancer ahead of his presentation at ESMO 2018.
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Chronic Lymphocytic Leukemia and Associated DisordersChronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western hemisphere, accounting for 30% of the leukemias in this population. The disease results from a clonal expansion of small B-lymphocytes. CLL always involves the bone marrow and peripheral blood. The disease also can be demonstrated in lymph nodes, liver, and spleen.
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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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UFT in Combination as Adjuvant Therapy for Breast CancerBetween 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a
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Understanding the Links Between Lung Cancer, COPD, and Emphysema: A Key to More Effective Treatment and ScreeningA better delineation of the relationships between lung cancer, COPD, and emphysema may lead to significant improvements in the effectiveness of lung cancer screening programs, and to reductions in the morbidity and mortality associated with these deadly diseases.
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Nivolumab Effective in Advanced Non-Squamous NSCLCIn this video, Dr. Paz-Ares discusses a phase III study that showed that nivolumab improved survival and response rates in previously treated patients with metastatic non-squamous non-small-cell lung cancer (NSCLC).
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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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How to Evaluate Risk and Identify Stage II Patients Requiring Referral to a Medical OncologistApproximately 150,000 new cases of colorectal cancer were expected for the year 2009 in the United States. Moreover, 49,920 deaths related to colorectal cancer were also predicted for the same year. The age-adjusted cancer death rates related to colorectal cancer have steadily declined over the past 2 decades. This improvement is a direct consequence of advances in prevention and treatment, including colorectal cancer screening, diagnostic tests, surgical technique, adjuvant therapies, and medical support.
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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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Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Emerging Treatment StrategiesOver the past decade, patients with locally advanced rectal cancer at The University of Texas M. D. Anderson Cancer Center have been managed with preoperative chemoradiation. Patients achieving a complete clinical response to preoperative chemoradiation have had better pelvic tumor control, sphincter preservation, and overall survival than those with gross residual disease. Some patients achieving a complete clinical response have even had rectal-preserving surgery (full-thickness local excision).
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UFT and Its Metabolites Inhibit Cancer-Induced Angiogenesis via a VEGF - Related PathwayTreatment with UFT for spontaneous lung metastasis of murine renal carcinoma (RENCA) after resection of the primary tumor has resulted in significant prolongation of the life span of tumor-bearing animals. UFT inhibited the growth of metastatic nodules in the lung, apparently via decreased density of microvessels in the metastatic foci. Subsequent experiments used dorsal air sac assay to directly trace newly forming microvessels.
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Surgical Management of Neuroendocrine Tumors of the Gastrointestinal TractThis article reviews the surgical management of gastrointestinal neuroendocrine tumors, including the preoperative control of hormonal symptoms, extent of resection required, postoperative outcomes, and differing management strategies as determined by whether the tumor has arisen sporadically or as part of a familial disorder, such as multiple endocrine neoplasia type 1.
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Use of Brachytherapy to Preserve Function in Children With Soft-Tissue SarcomasDr. Nag and colleagues present an excellent review of several of the techniques of brachytherapy used in both the pediatric and adult populations. The authors are to be commended for their comprehensive summary of the results of the major trials of pediatric brachytherapy in the management of soft-tissue sarcomas.
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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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Concurrent Chemotherapy and Radiotherapy in Patients With Brain TumorsBecause treatment for most brain tumors remains inadequate, there has been a sustained interest in using concurrent chemotherapy and radiotherapy to improve local control, prolong overall survival, and reduce
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Cancer Stem CellsTreatments that target cancer stem cells have been proposed as alternatives to current cancer therapies. However, the clonal evolution model suggests that multiple tumor cell populations may need to be targeted for these treatments to be successful.
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Questions We Should Be Asking About Bevacizumab for Cervical CancerThere is good evidence that angiogenesis plays a central role in cervical cancer pathogenesis, suggesting a strong rationale for adding anti-angiogenesis agents to chemotherapeutic agents for the treatment of this disease.
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Update on Malignant MesotheliomaMesotheliomas are uncommon in the United States, with an incidenceof about 3,000 new cases per year (or a risk of about 11 per million Americansper year). Incidence and mortality, however, are probably underestimated.Most are associated with asbestos, although some have arisen inports of prior radiation, and a reported association with simian virus (SV)40remains controversial. About 85% of mesotheliomas arise in the pleura,about 9% in the peritoneum, and a small percentage in the pericardiumor tunica vaginalis testis. The histology of about half of mesotheliomas isepithelial (tubular papillary), with the remainder sarcomatous or mixed.Multicystic mesotheliomas and well-differentiated papillary mesotheliomasare associated with long survival in the absence of treatmentand should be excluded from clinical trials intended for the usual rapidlylethal histologic variants of the disease. The median survival isunder a year, although longer median survivals for selected patients,particularly those with epithelial histology, have been reported in somecombined-modality studies. Recent randomized trials have shown significantimprovement in time to progression and survival for the additionof new antifolates to platinum-based chemotherapy.
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Lobular Neoplasia: How to Manage With Partial UnderstandingIn this issue of ONCOLOGY, Drs Oppong and King provide an organized and comprehensive summary of guidelines for the clinical management of patients with lobular carcinoma in situ (LCIS).
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Diagnosis and Management of Mycosis FungoidesMycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a low-grade cutaneous lymphoma characterized by skin-homing CD4+ T cells. It is notable for highly symptomatic progressive skin lesions, including patches, plaques, tumors, and erytheroderma, and has a poorer prognosis at later stages. Diagnosis remains difficult owing to MF’s nonspecific skin presentation and identification of the optimal treatment strategy is challenging given the paucity of controlled trials and numerous and emerging treatment options. Management includes topical therapy with the addition of systemic therapy for patients with later-stage disease including tumors; erythroderma; and nodal, visceral, or blood involvement. Topical therapies include mechlorethamine (nitrogen mustard), carmustine (BCNU), steroids, bexarotene gel (Targretin Gel), psoralen plus ultraviolet A (PUVA), ultraviolet B (UVB), and either localized or total skin electron radiotherapy. Systemic therapies include interferon, retinoids, oral bexarotene (Targretin), denileukin diftitox (Ontak), vorinostat (Zolinza), extracorporeal photochemotherapy (photopheresis), and cytotoxic chemotherapy. Herein, we outline clinically relevant aspects of MF, including clinical presentation, pathology, diagnosis, and staging. We describe in detail existing and emerging therapeutics and offer specific recommendations for management of each stage of MF.
