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Quality of Life After Radiation Therapy for Base of Tongue CancerQuality-of-life (QOL) research in patients treated for head and neck cancer is in its infancy. Early research focused on psychosocial issues related to extensive surgical resection and its consequences. Many advances
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Breast Cancer Stem Cells: A New Target for TherapyThe cancer stem cell (CSC) theory was first proposed to explain the fact that only a small proportion of leukemia or solid tumor cells have the capacity to induce growing tumors in immunodeficient mice.[1,2]
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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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Pemetrexed in Gastric CancerGastric cancer is a major clinical challenge, with poor overall prognosisand limited life expectancy for patients with advanced disease.Even with surgery and other modalities, palliation is often difficult.Improvement of response rates has evolved with the development ofstandard regimens and those incorporating newer chemotherapy agents,such as oral fluoropyrimidines, the taxanes, camptothecins, novel platinums(eg, oxaliplatin [Eloxatin]), and antifolates (eg, pemetrexed[Alimta]). Ongoing trials with these regimens aim toward improvingsurvival, as well as improving the safety profile. It is hoped that in conjunctionwith molecular research in the pathogenesis of gastric cancerand development of targeted therapies in this disease, these trial datamight lead to the evolution of treatment strategies that could prove effective.
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EGFR Inhibitors in Lung CancerTargeted therapies inhibiting the epidermal growth factor receptor(EGFR) have been introduced in the treatment of patients with advancednon–small-cell lung cancer (NSCLC). Many inhibitors of theEGFR have been developed, targeting either the extracellular receptordomain with antibodies or the intracellular tyrosine kinase bindingdomain with small molecules. The tyrosine kinase inhibitor (TKI)gefitinib (Iressa) was the first targeted drug to be registered for thetreatment of NSCLC after failure of chemotherapy. Given concurrentlytogether with platinum combination chemotherapy both TKIs gefitiniband erlotinib (Tarceva) failed to increase activity. Sequential targetedtherapy after chemotherapy is currently being investigated further. Studieswith the monoclonal antibody cetuximab (Erbitux) combined withchemotherapy are ongoing. Side effects of the small molecules aremainly skin rash and diarrhea, whereas the antibodies do not give diarrhea.Selection of patients, based on molecular markers and patientcharacteristics, has become an important issue for the further developmentof these drugs, given there is activity in a relatively small group ofpatients with NSCLC. Newer drugs inhibiting more than one receptorpathway are being investigated in order to find activity in a broadergroup of patients.
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Key Issues in Treating Frail Elderly Breast Cancer PatientsBy the year 2030 most patients with breast cancer will be aged 65 years or more and many will be frail. Frailty implies diminished physiologic reserve; contributors include diminished organ function, comorbidities, impaired physical function, and geriatric syndromes. Time-efficient tools for assessing frailty are being developed and, once validated, can be used to identify frail cancer patients and help direct therapy. Screening mammography in frail patients is questionable, and a clinical breast exam is likely to identify breast cancers that warrant intervention. Hormonal therapy may be a reasonable primary therapy in older frail women with hormone receptor–positive lesions. For estrogen receptor– and progesterone receptor–negative lesions, excision of the primary tumor may be adequate. Adjuvant hormonal therapy may be appropriate in frail elders with high-risk hormone receptor–positive breast cancer; chemotherapy is rarely indicated regardless of tumor status. The majority of frail elders with metastases will have hormone receptor–positive breast cancers, and endocrine therapy should be considered; those with receptor-negative tumors may be treated with single-agent chemotherapy or supportive care measures. Oncologists need to acquire the skills to appropriately identify frail elders so they select appropriate therapies that will minimize toxicity and maintain quality of life.
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Evaluating Advanced Technologies in Radiation Oncology: When and How Should Randomized Trials Be Done?The ultimate goal of radiation therapy (RT) is to deliver enough radiation to eradicate all tumor clonogens within the irradiated field while also minimizing dose to adjacent normal structures so as to cause no (or minimal) normal tissue injury. With few exceptions, the dose of radiation currently delivered to most anatomic sites is limited by the tolerance of these adjacent normal organs, thereby restricting the dose of radiation deposited in tumors to an amount that may or may not be ideal to realize an optimal cure. The goal of many advanced technologies introduced into RT are aimed at addressing this problem.
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Docetaxel in Combination With Flourouracil: Study Design and Preliminary ResultsThe relatively recent introduction of a new class of chemotherapeutic agents--the taxoids--has raised hope of improved survival for patients with advanced or metastatic cancer. Following encouraging preclinical results of taxoid combinations, this phase I, nonrandomized trial was designed to evaluate a 1-hour intravenous infusion of docetaxel (Taxotere) on day 1 combined with fluorouracil (5-FU) as a daily intravenous bolus for 5 consecutive days.
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From Radiotherapy to Targeted Therapy: 20 Years in the Management of Non-Small-Cell Lung CancerNon-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Before 1980, radiotherapy was considered the only real recourse in advanced disease. In 1995, a landmark meta-analysis of trials conducted in the 1980s and early 1990s demonstrated a survival benefit with platinum-based chemotherapy. Newer chemotherapy agents and improved supportive care measures have allowed more patients to benefit from chemotherapy with reduced toxicity. Concurrent platinum-based chemotherapy and radiotherapy has improved the survival in stage III disease, and recently chemotherapy has also demonstrated improved survival in resected early-stage disease. The majority of patients still present with advanced unresec disease for whom the prognosis remains poor, but for key subpopulations the outlook has improved markedly since the emergence of targeted therapies directed against the epidermal growth factor receptor and vascular endothelial growth factor receptor pathways. Patient selection and the incorporation of targeted therapies with cytotoxic chemotherapy are the focus of many ongoing studies, and there is an abundance of new agents undergoing clinical trials. Together, these developments have moved us away from the nihilism of 20 years ago into an era of unprecedented optimism in taking on the many remaining challenges of managing NSCLC in the 21st century.
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Prostate Cancer in the Older ManMost men diagnosed with prostate cancer are more than 65 years of age. Therefore, a discussion of the issues surrounding the diagnosis, prevention, and treatment of prostate cancer in older men is, in many ways, a review of
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Bevacizumab and Glioblastoma: The Ecstasy and the AgonyThe absence of any effective combinatorial therapy in patients progressing on bevacizumab and evidence supporting both continuation and discontinuation of bevacizumab in this setting remain important areas for additional clinical trial evaluation in order to better guide our therapeutic decision making in the clinic.
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Response to Antiangiogenesis Therapy in a Patient With Advanced Adult-Type Testicular Granulosa Cell TumorWe have presented the first case of a patient with metastatic ATGCT with peritoneal carcinomatosis, who responded to treatment with a VEGFR tyrosine kinase inhibitor. Because of the relative paucity of such cases in the literature, no clear treatment strategy exists. For patients with metastatic ATGCT, enrollment in clinical trials testing novel therapies, including angiogenesis inhibitors, is a reasonable option.
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Understanding Novel Molecular TherapiesThe science supporting molecularly targeted therapies for the treatment of patients with solid tumors continues to evolve. Nurses are challenged to understand cell signaling, molecular targeting, and the mechanism of action of targeted agents. Two cell signal transduction pathways regulate the development, proliferation, and metastasis of solid tumors: the human epidermal growth factor (HER) receptor pathway and the vascular endothelial growth factor (VEGF) receptor pathway. Several novel pharmacologic agents with distinct indications and methods of administration target the HER and VEGF molecular pathways.
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Tumor Heterogeneity Is Fundamental to the Tumor EcosystemIt may be necessary to broaden our concept of the malignant process beyond that of a disease to be attacked-to one that reflects a deeper understanding of the fundamentals of living systems.
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Genetic Testing and Counseling in Familial Adenomatous PolyposisTesting for adenomatous polyposis coli (APC), the gene responsible for familial adenomatous polyposis (FAP), can now be offered to family members in FAP kindreds. With the availability of this test, genetic counseling has become a crucial tool for helping FAP patients and their relatives understand the syndrome and its implications and for assisting at-risk individuals in making informed decisions about whether or not to undergo genetic testing. Genetic counseling can occur at several time points: when FAP is diagnosed, when an FAP patient is considering reproductive options, when a patient is deciding whether to have his or her children screened, and when an at-risk person is considering genetic testing.
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UFT: Mechanism of Drug ActionThe mechanism of action of fluorouracil (5-FU) and the oral fluoropyrimidines and the importance of biochemical modulation and inhibition of dihydropyrimidine dehydrogenase for oral application of the prodrugs of 5-FU are discussed.
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Treatment of Complications After Breast-Conservation TherapyOver the past 2 decades, breast-conservation therapy with lumpectomyand whole-breast radiotherapy has become a standard option for themajority of women with newly diagnosed breast cancer. Long-term localcontrol is achieved in approximately 85% of patients, and the therapy isgenerally well tolerated. There can, however, be long-term effects on thebreast and other nearby tissues that may range from asymptomaticfindings on examination to severe, debilitating problems. Infection, fatnecrosis, and severe musculoskeletal problems such as osteoradionecrosisor soft-tissue necrosis are uncommon, affecting less than 5% ofpatients. However, changes in range of motion, mild-to-moderate musculoskeletalpain, and arm and breast edema are much more common.As more women choose breast-conservation therapy for management oftheir breast cancer, physicians will encounter these problems, as well asin-breast tumor recurrence, with greater frequency. This review willfocus on the incidence, contributing factors, and management of thelate problems of infection, fat necrosis, musculoskeletal complications,and local recurrence following breast-conservation therapy.
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Acute Myeloid Leukemia: The Challenge of Unfavorable CytogeneticsPrognostic factors in acute myeloid leukemia (AML) may be subdivided into those related to patient characteristics and general health condition, and those related to characteristics of the tumor.
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Vaccine Therapy, Oncolytic Viruses, and GliomasIn this article, we will discuss some of the vaccination and oncolytic virus strategies being evaluated in the clinic for malignant gliomas. The vaccines reviewed here include the cell-based and the non–cell-based.
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A 54-Year-Old Woman With Recurrent Headaches and SeizuresThe patient’s medical history is remarkable only for asthma and mild emphysema. The family history included a grandmother with gastric cancer. The patient had been taking estrogen replacement therapy since menopause 3 years earlier, and she was
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Tandem Transplantation in Multiple MyelomaThe use of high-dose chemotherapy and autologous stem cellsupport in the past decade has changed the outlook for patients withmultiple myeloma. In newly diagnosed patients, complete remissionrates of 25% to 50% can be achieved, with median disease-free andoverall survivals exceeding 3 and 5 years, respectively. Despite theseresults, autologous transplantation has not changed the ultimatelyfatal outcome of the disease, as there is no substantial evidence of“cure” in most published studies. An additional high-dose chemotherapycourse (with tandem transplants) appears to improve progressionfreesurvival, although the effect is not discernible until 3 to 5 yearsposttransplant. The recent reports of tandem autologous transplant formaximum cytoreduction followed by nonmyeloablative allogeneictransplant for eradication of minimal residual disease appears promisingand deserve further investigation. A central issue of tandemtransplants, whether they involve autologous or allogeneic transplants,revolves around defining the subsets of patients who will benefitfrom the procedure. Good-risk patients (defined by normal cytogeneticsand low beta-2–microglobulin levels), especially those who achievea complete or near-complete response after the first transplant, appearto benefit the most from a second cycle. High-risk patients (defined bychromosomal abnormalities usually involving chromosomes 11 and 13and high beta-2–microglobulin levels) whose median survival aftertandem transplant is less than 2 years should be offered novel therapeuticinterventions such as tandem “auto/allo” transplants. Until theefficacy and safety of this procedure is fully established, it should belimited to high-risk patients.
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Homologous Recombination Deficiency and PARP Inhibition in Ovarian CancerAs part of our coverage of the 2017 ASCO Annual Meeting, we discuss homologous recombination deficiency in ovarian cancer and PARP inhibitors.
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Gemcitabine in Combination With Trastuzumab and/or Platinum Salts in Breast Cancer Cells With HER2 OverexpressionTrastuzumab (Herceptin) is an effective treatment in patients withHER2-overexpressing metastatic breast cancer. Risk of trastuzumabinducedcardiotoxicity raises concerns regarding combined use withanthracyclines or other potentially cardiotoxic agents followinganthracycline treatment. We characterized interactions betweentrastuzumab and gemcitabine (Gemzar) and the combination ofgemcitabine and cisplatin or carboplatin (Paraplatin) as such combinationsmight help reduce the risk of cardiotoxicity. Multiple drugeffect/combination index isobologram analysis was used to study theefficacy of chemotherapeutic drug plus trastuzumab combinations inHER2-overexpressing breast cancer cell lines. Combination index valueswere derived from parameters of the median effect plots, and statisticaltests were used to determine whether the mean combinationindex at multiple effect levels significantly differed from a combinationindex value of 1.0 (values < 1.0 indicate synergy; values > 1.0,antagonism; values equal to 1.0, additivity). At a wide range of clinicallyachievable drug concentrations, interactions between trastuzumaband gemcitabine were synergistic at low concentrations of gemcitabineand antagonistic at high concentrations. A consistent synergistic interactionwas observed with the three-drug combination of trastuzumabplus gemcitabine plus carboplatin or cisplatin. Available clinical dataon the use of trastuzumab plus gemcitabine, and trastuzumab plusgemcitabine/paclitaxel, as well as clinical data on the use ofgemcitabine/cisplatin in breast cancer, are discussed. These findingsindicate that trastuzumab plus gemcitabine and trastuzumab plusgemcitabine plus cisplatin or carboplatin are rational combinations toevaluate in clinical trials.
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Role of Obesity and Exercise in Breast Cancer SurvivorsAfter malignancies of the skin, breast cancer is the most common cancer
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Fraudulent Interpretation of Lab ResultsIn this edition, we offer an example of how clinicians and patients can be fooled and/or injured by fraudulent healthcare practitioners and their services. The clinical care team must be sure that the references it provides to patients are safe and reliable. Keep a list of reliable references and a list of those practitioners and services/treatments that should be avoided. Maintain an open door policy with your patients designed to encourage questions and exchange such information.
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A Strong Dose of HubrisFDA recently came close to taking away hope for thousands of terminally ill women. But at the last minute, the agency announced it was postponing until December whether to revoke approval of Avastin for advanced-stage breast cancer treatment.
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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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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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Exercise in Regulation of Inflammation-Immune Axis Function in Cancer Initiation and ProgressionThis article provides an overview of the current state of knowledge pertaining to exercise modulation of the inflammation-immune axis in cancer. The current evidence suggests that exercise may be a promising adjunctive strategy that can favorably alter numerous components of the immune system, which, in turn, may modulate tumorigenesis.
