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Adjuvant Chemotherapy for Early-Stage Breast Cancer: The tAnGo TrialThe tAnGo trial is a randomized, open-label, multicenter phase IIItrial examining adjuvant treatment with epirubicin (Ellence)/cyclophosphamide(Cytoxan, Neosar) for four cycles followed by paclitaxel aloneor combined with gemcitabine (Gemzar) for four cycles in patients withearly-stage breast cancer. In the Cancer and Leukemia Group B(CALGB) 9344 trial, addition of paclitaxel to anthracycline/cyclophosphamideadjuvant therapy resulted in increased time to recurrence andimproved survival. Because an unplanned subgroup analysis in CALGB9344 indicated a significant benefit of paclitaxel in patients with estrogenreceptor (ER)-negative disease but not ER-positive disease, the initialtAnGo trial design called for enrollment of patients with ER-negativedisease. The tAnGo trial entry criteria were recently amended toallow any ER status, given experience suggesting that clinical benefitof taxane-containing regimens in ER-positive disease may emerge overa time frame longer than that required to detect benefit in ER-negativedisease. Gemcitabine has been included as a partner for paclitaxel inthe tAnGo trial based on high response rates, including high completeresponse rates, observed in phase II trials of the combination in moreadvanced disease and based on the tolerability and safety of the combinationcompared with those of other taxane-containing two-drug combinations.The tAnGo trial is currently accruing patients and has atarget population of 3,000. Trial results should provide important informationon the role of gemcitabine in adjuvant therapy for breastcancer.
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Apoptotic Mechanisms of Gallium Nitrate: Basic and Clinical InvestigationsGallium nitrate inhibits the growth of various lymphoma cell linesin vitro and exhibits antitumor activity in patients with lymphoma.The mechanism(s) of cytotoxicity is (are) only partly understood butappears to involve a two-step process: (1) targeting of gallium to cells,and (2) acting on multiple, specific intracellular processes. Galliumshares certain chemical properties with iron; therefore, it binds avidlyto the iron transport protein transferrin. Transferrin-gallium complexespreferentially target cells that express transferrin receptors on theirsurface. Expression of transferrin receptors is particularly high onlymphoma cells. Cellular uptake of the gallium-transferrin complexleads to inhibition of cellular proliferation primarily via disruption ofiron transport and homeostasis and blockade of ribonucleotidereductase. Recent studies have shown that cellular uptake of galliumleads to activation of caspases and induction of apoptosis. In phase IItrials in patients with relapsed or refractory lymphoma, the antitumoractivity of gallium nitrate is similar to, or better than, that of othercommonly used chemotherapeutic agents. Gallium nitrate is notmyelosuppressive and may be used in patients with neutropenia orthrombocytopenia. A multicenter trial to evaluate the use of galliumnitrate in patients with relapsed non-Hodgkin's lymphoma is currentlyongoing.
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Supporting Decision-Making on Fertility Preservation Among Adolescent and Young Adult Women With CancerABSTRACT Adolescents and young adults (AYAs) with cancer constitute approximately 70,000 patients diagnosed each year. Survival rates for AYAs with cancer have increased steadily in recent decades due to improvements in therapeutic regimens and early detection. Given the large and growing number of AYA cancer survivors, additional research is needed on the immediate and long-term psychosocial support required for this population including family planning and fertility. Fertility and fertility preservation in female AYAs, in particular, is historically understudied and has psychologically relevant ramifications distinct from male AYAs. Decision science can contribute to this area of oncological care and has implications for clinical encounters and research concerning female AYA patients with cancer. Patient-centered care and shared decision-making that integrates recent research regarding fertility preservation in the context of cancer treatment can improve outcomes for AYA cancer survivors.
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Bacterial Infections in Patients With Solid TumorsEarly and appropriate management of infection in the patient with cancer is critical to optimizing patient outcomes.
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The State of Prostate MRI in 2013Our aims in this article are to describe the various imaging sequences that comprise the multiparametric MRI exam, as well as to review current literature on the strengths/weaknesses of these sequences; to delineate strategies for standardizing interpretation and reporting of MRI results; and to expound on the role of prostate MRI in clinical practice.
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Radiation-Induced Lung Injury: Assessment, Management, and PreventionRadiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.
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Use of Neoadjuvant Chemotherapy in Elderly Patients With Muscle-Invasive Bladder Cancer: A Population-Based Study, 2006-2017Patients 70 years or older that received neoadjuvant chemotherapy and radical cystectomy had better overall survival than those undergoing radical cystectomy alone.
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Challenges to the FDA Review Process: Cost Considerations and Long-Term Benefit BenchmarksIn this interview, Christopher-Paul Milne and Kenneth Kaitin, Tufts Center for the Study of Drug Development. discuss the current challenges of the US Food and Drug Administration review process as it relates to oncology therapeutics and upcoming changes to the Prescription Drug User Fee Act.
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Pathogenesis of AIDS-Related Kaposi's SarcomaThe occurrence of Kaposi's sarcoma (KS) in patients with HIV infection is more than 7,000 times higher than in the non-HIV infected population. The reason for this association is unclear but may involve decreased immune surveillance as a result of the profound cellular immune deficiency caused by HIV, a sexually transmitted KS-inducing virus, whose KS-transforming capabilities may be enhanced by HIV, or a direct or indirect effect of HIV itself in susceptible individuals.
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Gemcitabine and Platinum-Based Chemotherapy in Metastatic Breast CancerAlthough anthracyclines and the taxanes comprise the most activefirst-line cytotoxic treatments in patients with hormone-insensitive orlife-threatening metastatic breast cancer, many patients progress andrequire other chemotherapeutic agents. Development of new combinationsand/or agents is thus needed. Gemcitabine (Gemzar) and platinumcompounds have been employed as single agents, and the additionof gemcitabine to the platinums results in significant clinical benefitand response rates. Correlative biologic studies are expected fromseveral already-reported trials and may help elucidate predictive factorsfor both response and toxicity when combining gemcitabine andthe platinums. Trials incorporating these doublets in earlier stages ofbreast cancer or in the neoadjuvant setting may further elucidate theirrole in breast cancer treatment.
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ACR Appropriateness Criteria® Recurrent Hodgkin LymphomaBy combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decision-making associated with the management of recurrent Hodgkin lymphoma.
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Irinotecan/Cisplatin in Advanced, Treated Gastric or Gastroesophageal Junction CarcinomaWe conducted a phase II study to assess the response rate and toxicity profile of the irinotecan (CPT-11, Camptosar) plus cisplatin combination administered weekly to patients with at least one previous chemotherapy for advanced adenocarcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach or gastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 50 mg/m² of irinotecan plus 30 mg/m² of cisplatin, both administered intravenously 1 day a week for 4 consecutive weeks, followed by a 2-week recovery period.
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Pertuzumab and Its Accelerated Approval: Evolving Treatment Paradigms and New Challenges in the Management of HER2-Positive Breast CancerThis article discusses the development of pertuzumab to date, with a particular focus on the accelerated approval decision. We highlight the need to identify reliable biomarkers of sensitivity and resistance to HER2-targeted therapy, which would make possible the individualization of treatment for patients with HER2-positive breast cancer.
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The Continuing Challenge of Metastatic Breast CancerBreast cancer is the most common cancer in women living in the developed world. One in eight women will be diagnosed with breast cancer during their lifetime. The majority of newly diagnosed patients have early-stage disease.
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When Is it Justified to Treat Symptoms? Measuring Symptom BurdenSymptom burden is certainly not a new concept in the literature on disease and treatment, but recent developments in our understanding of how to measure symptoms and their impact make it possible to cast symptom burden as a reasonable summary measure of both disease- and treatment-outcome status. We discuss the use of symptom burden as an alternative to quality-of-life measures or as a supplement to these measures.
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Paclitaxel and Vinorelbine in Non-Small-Cell Lung CancerPaclitaxel (Taxol) and vinorelbine (Navelbine) are both microtubule toxins but with opposite mechanisms of action. Paclitaxel promotes the assembly of microtubules, whereas vinorelbine prevents microtuble assembly.
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Current Status of Genetic Testing for Colorectal Cancer SusceptibilityOver 130,000 new cases of colon cancer are diagnosed annually. Approximately 20% to 30% of these are attributable to familial risk, and 3% to 5% belong to a hereditary colorectal cancer predisposition syndrome.
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Commentary (Basen-Engquist/Cohen): Quality of Life in Low-Grade Non-Hodgkin’s LymphomaCancer treatment often has debilitating effects on the patients who receive it. Chemotherapy regimens can produce toxicities, such as gastrointestinal disturbances, hematologic deficiencies, fatigue, and neurotoxicity. Patients typically undergo these chemotherapy regimens to increase their disease-free survival time. Given that these therapies can negatively affect a patient’s quality of life (QOL), treatments need to provide clear curative potential and/or survival benefits to offset detrimental effects on QOL.
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Current Standards and Novel Treatment Options for Metastatic Pancreatic AdenocarcinomaThis article reviews the current treatment paradigms for metastatic disease, focusing on ways to ameliorate symptoms and lengthen survival. We then summarize recent advances in our understanding of the molecular and cellular aspects of pancreatic cancer.
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UFT/Leucovorin in Advanced Squamous Cell Carcinoma of the Head and Neck Administered With RadiotherapyThis is an open-label, nonrandomized phase I study to determine the maximum tolerated dose and dose-limiting toxicity of UFT plus leucovorin when given concomitantly with hyperfractionated radiotherapy in patients with head and neck cancer. The study period is determined by the course of radiotherapy, which is given as 1.7 Gy per fraction twice daily for 5 days (Monday to Friday) in 2 consecutive weeks, followed by 1 week of rest, and subsequently another 2 weeks of radiotherapy (Monday to Friday plus Monday to Thursday).
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Is There a Role for Hemopoietic Stem-Cell Transplantation in CTCL?The role of autologous and allogeneic stem-cell transplantation (SCT) in the treatment of cutaneous T-cell lymphoma (CTCL) is reviewed. Patients most likely to benefit are those with advanced-stage disease, multiple relapses, and short remissions; chemosensitive disease is also a prerequisite for these treatments. Autologous SCT produces high response rates in patients with peripheral T-cell lymphoma, but these are generally of short duration. This therapy is relatively safe to administer, with little transplant-related mortality. In contrast, allogeneic SCT may be highly toxic and result in transplant-related mortality, but it has the potential to produce long-lasting responses. Prospective studies of these treatments in patients with CTCL are required. Nevertheless, selected patients could be considered for allogeneic SCT, preferably early in their disease when their performance status is still good.
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New Strategies for Managing Metastatic Breast CancerDrs. Olin and Muss provide an excellent review of current state-of-the-art treatments and treatment strategies for patients with metastatic breast cancer. They explore a number of the existing questions in the treatment of metastatic breast cancer and emphasize the need for ongoing clinical trials.
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Unraveling the Mystery of a Supraclavicular MassIn this month’s Clinical Quandaries case report, a 49-year-old man was diagnosed with an extragonadal seminoma. The diagnosis was made on a fine-needle aspiration of a 7-cm supraclavicular mass. Beta–human chorionic gonadotropin and alpha-fetoprotein levels were normal. The only cancer history for this patient was a basal cell carcinoma of the nose. The patient complaints were fatigue; sensory and motor dysfunction in the hands, legs, and abdomen; unsteady gait; and blurry vision.
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Unrelated Donor StemCell Transplantation: The Role of the National Marrow Donor ProgramApproximately 70% of patientswith life-threatening diseasestreatable with allogeneic bloodstem cell transplantation do not havematched related donors. The NationalMarrow Donor Program (NMDP) wasestablished in 1986 to provide humanleukocyte antigen (HLA)-matched,volunteer unrelated donors for thesepatients. The NMDP performs thistask by maintaining a registry of morethan 4.9 million volunteer donors ofmarrow and peripheral blood stemcells (PBSC) and 12 cord blood bankscontaining more than 25,000 units ofumbilical cord blood.
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Acute Myeloid Leukemia With Adverse Cytogenetic RiskAcute myeloid leukemia (AML) encompasses multiple disease entities that differ with regard to marrow morphology, cytochemistry, immunophenotype, pretreatment clinical characteristics, and treatment outcome.
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Changing Concepts in the Management of Endometrial CancerEndometrial carcinoma was a clinically staged disease until the late 1980s, at which point, staging changed to a surgicopathologically defined system. This change in staging, in turn, altered the clinical management of this
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Targeted Focal Therapy: A Small Step ForwardThe morbidities associated with prostate cancer treatments have improved over the years. However, potential overtreatment and the risks of adverse events associated with radical treatment still pose a considerable challenge. Targeted focal therapy (TFT) of prostate cancer appears to be part of a logical continuum in the quest to improve upon the management of early organ-confined disease. TFT is a procedure in which only the cancer in the gland is ablated. The normal gland, sphincter, and in most cases the neurovascular bundles are preserved. Therefore, this approach averts some of the common complications of more radical therapy. Initial experience has been encouraging; however, long-term data and full implementation of emerging advances in imaging are urgently needed before the widespread adoption of this approach. In this review, we present the current status of our knowledge about this procedure and the most important challenges that need to be addressed. We also present the initial results with this approach at our center.
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Management of Infections in Patients With Acute LeukemiaSeveral recent studies have addressed the management of infectious problems in patients with acute leukemia. Although those studies have served to emphasize the fundamental management principles formulated and proven
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Natural History and Treatment of Malignant ThymomaThymomas are rare, slow-growing neoplasms that are considered to be malignant because of their potential invasiveness. The most widely used staging system is that of Masaoka and colleagues, which takes into account
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Health-Related Quality of Life in Cancer Prevention Clinical TrialsClinical trials of agents to prevent cancer in populations at risk are relatively recent. To date, these consist of a few large population-based studies. Trials in this area focus on the prevention of cancer in individuals with specific predetermined risk
