bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique Features of the Mode of Action of ET-743
Authors: D'Incalci Maurizio , Erba Eugenio , Damia Giovanna , Galliera Emanuela , Carrassa Laura , Marchini Sergio , Mantovani Roberto , Tognon Gianluca , Fruscio Robert , Jimeno José , Faircloth Glynn T. 
Published: August 2004

Abstract
This paper describes the current knowledge of the primary mode of action of a natural product, ecteinascidin 743 (ET-743), derived from the marine tunicate Ecteinascidia turbinata. ET-743 was initially selected for preclinical development because of its potent antitumor activity observed against several human solid tumor types. In vitro, the drug is cytotoxic in the nanomolar range, and in the case of some very sensitive cell lines, in the picomolar range. The large potency differences observed among several solid tumor types indicate that this compound possesses some tumor selectivity, but the molecular basis of these differential effects remains to be elucidated. The present studies were undertaken to evaluate the mechanism of action of ET-743 in this context. The available information on ET-743 binding to DNA and its effects on transcriptional regulation point to a unique behavior of this drug, as it independently affects specific gene transcription in a promoter-dependent way. In addition, ET-743 shows a peculiar pattern of selectivity in cells with different defects in their DNA-repair pathways. These results highlight a unique property of ET-743, possibly explaining why it possesses antitumor activity against tumors that are refractory to standard anticancer drugs, all of which certainly act by mechanisms that are different from that of ET-743.
Progress and Promise in the Treatment of Indolent Lymphomas
Authors: McLaughlin Peter 
Published: August 2004

Abstract

Learning Objectives

After completing this course, the reader will be able to:
Describe subsets of patients with indolent lymphoma for whom cure may be a realistic goal. Describe the ways by which the polymerase chain reaction for bcl-2 can be utilized to monitor patients with follicular lymphoma. Identify immunotherapy approaches that have shown promising results for patients with indolent lymphoma.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
In the era of conventional alkylating agent-based chemotherapy, advanced stage indolent lymphoma has been considered incurable. The failure of our traditional therapies to cure these patients, coupled with the indolent course of the disease and the elderly population affected, has fostered a nihilistic attitude about the treatment of these diseases. Twenty years ago, in the absence of interesting alternatives to alkylating agents, judicious use and reuse of alkylators was perhaps the best we could do. There are now many reasons for optimism and excitement in the treatment of these diseases, including the availability of promising agents such as interferon-α, the nucleoside analogues, and rituximab. Radioimmunotherapy will also likely play a role in future therapy programs. Allogeneic stem cell transplantation is a high-risk approach that is not an option for all patients, but it has the potential to cure patients, even in the setting of relapse. Mini-allogeneic transplantation may permit an approach to allogeneic transplantation that is better tolerated than standard transplant strategies. In addition to these therapy options, biological insights have provided new options for monitoring patients. Molecular monitoring (polymerase chain reaction for bcl-2) is a stringent measure of short-term treatment efficacy, and one that correlates with durability of remission, i.e., it is a surrogate marker by which to judge treatment efficacy. There used to be a limited number of conventional treatment approaches, which consistently failed. The pendulum has swung. There are now many promising new options. It is time to plan and conduct trials that are geared for success.
Is There a Preferred Combination Chemotherapy Regimen for Metastastic Non-Small Cell Lung Cancer?
Authors: Ettinger David S. 
Published: August 2004

Abstract

Learning Objectives

After completing this course, the reader will be able to:
Choose the appropriate chemotherapeutic regimen to treat a patient with metastatic non-small cell lung cancer. Identify the advantages and disadvantages of the various regimens to treat stage IV non-small cell cancer. Understand the toxicities associated with each of the various chemotherapeutic regimens.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Since over 70% of patients with non-small cell lung cancer (NSCLC) have advanced (locally advanced or metastatic) disease, the majority of NSCLC patients might benefit from chemotherapy. During the past decade, a number of new agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan) have been found to be effective against lung cancer. These agents have been combined with cisplatin, carboplatin, and nonplatinum drugs to treat NSCLC. They, in general, produce median survival times of 8-10 months and 1- and 2-year survival rates of 35%-40% and 10%-15%, respectively. Based on this review, there is not a preferred combination chemotherapy regimen to treat advanced NSCLC patients. However, there are a number of different regimens from which to choose.
Small Cell Lung Cancer: Current Therapy and Promising New Regimens
Authors: Okuno Scott H. , Jett James R. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:

Understand the treatment options for limited versus extensive small cell lung cancer. Understand the role of prophylactic cranial irradiation for small cell lung cancer. Understand second-line chemotherapy regiments for small cell lung cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
In this review, we cover current therapy and promising new regimens and highlight areas where improvement is needed in the management of small cell lung cancer.
The Molecular Perspective: Bcl-2 and Apoptosis
Authors: Goodsell David S. 
Published: August 2004

Abstract

Learning Objective
After completing this course, the reader will be able to:
Gain a basic understanding of the structure and function of the bcl-2 family of proteins, and their place in apoptosis and cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Staging of Regional Nodes in AJCC Stage I and II Melanoma: 18FDG PET Imaging versus Sentinel Node Detection
Authors: Belhocine Tarik , Pierard Gérald , de Labrassinne Michel , Lahaye Thierry , Rigo Pierre 
Published: August 2004

Abstract
Primary Purpose. The staging of regional nodes by means of sentinel node detection has been shown to accurately detect subclinical nodal metastases from cutaneous melanoma. On the other hand, the oncological applications of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) are, nowadays, firmly established. However, the sensitivity of such metabolic imaging for staging the regional nodes in primary melanoma remains debatable. We prospectively assessed the actual value of PET for detecting sentinel node metastases in 21 consecutive patients presenting with early-stage melanoma.
Materials and Methods. Twenty-one melanoma patients scheduled for lymphatic mapping and sentinel lymphadenectomy underwent fully corrected whole-body PET using 18FDG. In all cases, the disease was initially classified as either stage I or II, from the latest version of the American Joint Committee on Cancer staging system. The sentinel node detection was systematically performed within the week following the PET scan. Serial sections of the sentinel nodes were analyzed by both conventional pathology and immunohistochemical staining. Metastatic sentinel nodes were also assessed for the size of tumor deposits and the degree of nodal involvement (focal, partial, or massive). The median follow-up time was 12 months.
Results. Six of the 21 patients (28.5%) had an involved sentinel node. PET was positive in only one case with a sentinel node &gt;1 cm. In the five other cases, the sentinel nodes missed by PET were &lt;1 cm with focal and/or partial involvements. One patient, free of regional nodal metastases in both sentinel node detection and PET imaging, had, however, a same-basin recurrence 3 months later. In another case, PET had one false positive result. Overall, the sentinel detection of subclinical nodal metastases had a sensitivity of 86%. PET detected only 14% of sentinel node metastases.
Conclusions. Sentinel node detection remains the procedure of choice for detecting subclinical lymph node involvement from primary cutaneous melanoma. Owing to its limited spatial resolution, PET appears insufficiently sensitive to identify microscopic nodal metastases. As a practical consequence, metabolic imaging is not recommended as a first-line imaging strategy for staging regional lymph nodes in patients with stage I or II melanoma.
Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review
Authors: Malet-Martino M. , Martino R. 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Define the main oral prodrugs of fluorouracil. Know the indications of the new oral prodrugs of fluorouracil. Review the main toxicities and drug interactions of oral prodrugs of fluorouracil. Evaluate the benefit(s) of using an oral prodrug of fluorouracil compared with classical treatments.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.comAlthough 5-fluorouracil (5-FU) was first introduced in 1957, it remains an essential part of the treatment of a wide range of solid tumors. 5-FU has antitumor activity against epithelial malignancies arising in the gastrointestinal tract and breast as well as the head and neck, with single-agent response rates of only 10%-30%. Although 5-FU is still the most widely prescribed agent for the treatment of colorectal cancer, less than one-third of patients achieve objective responses. Recent research has focused on the biomodulation of 5-FU to improve the cytotoxicity and therapeutic effectiveness of this drug in the treatment of advanced disease. As all the anticancer agents, 5-FU leads to several toxicities. The toxicity profile of 5-FU is schedule dependent. Myelotoxicity is the major toxic effect in patients receiving bolus doses. Hand-foot syndrome (palmar-plantar erythrodysesthesia), stomatitis, and neuro- and cardiotoxicities are associated with continuous infusions. Other adverse effects associated with both bolus-dose and continuous-infusion regimens include nausea and vomiting, diarrhea, alopecia, and dermatitis. All these reasons explain the need for more effective and less toxic fluoropyrimidines.In the first part of this review, we briefly present the metabolic pathways of 5-FU responsible for the efficacy and toxicity of this drug. This knowledge is also necessary to understand the target(s) of biomodulation.The second part is devoted to a review of the literature on three recent prodrugs of 5-FU, i.e., capecitabine, UFT (ftorafur [FTO] plus uracil), and S-1 (FTO plus 5-chloro-2,4-dihydroxypyridine plus potassium oxonate). The pharmacological principles that have influenced the development of these new drugs and our current knowledge of the clinical pharmacology of these new agents, focusing on antitumor activity and toxicity, are presented.The literature was analyzed until March 2002. This review is intended to be as exhaustive as possible since it was conceived as a work tool for readers wanting to go further.
Managing Anemia in the Cancer Patient: Old Problems, Future Solutions
Authors: Gordon Michael S. 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Identify potential benefits for EPO therapy beyond those of transfusions. Recognize the impact of EPO therapy on aspects of health-related quality of life. Appreciate recent advances in the field of hematopoietic growth factor support as it relates to anemia management.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.comAnemia and associated symptoms commonly manifest in cancer patients and may have a considerable impact on outcomes. Preliminary studies suggest that overall survival and locoregional control following radiation therapy may be compromised by anemia, and recent preliminary data also suggest that anemia may be related to poorer outcomes following chemotherapy. Health-related quality of life of cancer patients is also significantly reduced by anemia. Treatment of anemia with recombinant human erythropoietin can improve these health-related quality-of-life outcomes. However, despite this knowledge, anemia remains under-recognized and under-treated in the cancer patient population. A number of issues may be determinants of this suboptimal management of anemia. These include limitations of current therapies for anemia, varying practice strategies, and the lack of guidelines on how to treat anemia. Additionally, clinicians may underestimate the importance of health-related quality of life for their patients. It is vital that these issues are addressed, which, together with the development of novel erythropoietic agents, a review of the guidelines for anemia management, and consideration of further outcomes such as survival and cognitive function, may help to ensure that the cancer patient receives the best possible course of supportive care.
Faith, Identity, and Leukemia: When Blood Products are Not an Option
Authors: Knuti Kristine A. , Amrein Philip C. , Chabner Bruce A. , Lynch Thomas J. , Penson Richard T. 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Acknowledge the emotions (guilt, frustration, and anger)of caregivers treating patients with different world/religious viewsUnderstand the legal requirement to respect patient autonomy in medical decisions.Explore the influence of religious views on quality of life.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.comShortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members.When a competent adult patient refuses lifesaving treatment for religious or personal reasons, caregivers have a legal obligation to respect this decision. A patient's refusal of treatment adds particular challenges to the delivery of compassionate care. The case of a 50-year-old Jehovah's Witness with acute myelocytic leukemia who declined blood product support is presented. Respecting her religious beliefs during chemotherapy required balancing risk and benefit, watching her suffer while unable to intervene with what the staff saw as simple treatment, and eventually undertaking a complicated grief process. Jehovah's Witness beliefs regarding blood products are reviewed. Caregiver roles and responsibilities are discussed in the context of psychosocial, legal, familial, and ethical issues.
The Molecular Perspective: DNA Topoisomerases
Authors: Goodsell David S. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Gain a basic understanding of the structure and function of the DNA topoisomerases and their place as targets for chemotherapy.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Gleevec™ for the Treatment of Chronic Myelogenous Leukemia: U.S. Food and Drug Administration Regulatory Mechanisms, Accelerated Approval, and Orphan Drug Status
Authors: Cohen Martin H. , Moses Marie L. , Pazdur Richard 
Published: August 2004

Abstract
Gleevec™ (imatinib mesylate), a highly promising new drug for the treatment of chronic myelogenous leukemia in blast crisis, in accelerated phase, and in chronic phase after interferon failure or intolerance, received orphan drug status from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development on January 31, 2001, and accelerated approval from the FDA for the above three indications on May 10, 2001. The purpose of this report is to summarize FDA regulatory mechanisms, i.e., accelerated approval and orphan drug regulations, that have permitted patients to receive this drug as rapidly as possible.
U.S. Food and Drug Administration Drug Approval Summaries: Imatinib Mesylate, Mesna Tablets, and Zoledronic Acid
Authors: Cohen Martin H. , Dagher Ramzi , Griebel Donna J. , Ibrahim Amna , Martin Alison , Scher Nancy S. , Sokol Gerald H. , Williams Grant A. , Pazdur Richard 
Published: August 2004

Abstract
The purpose of this report is to summarize information on drugs recently approved by the U.S. Food and Drug Administration. Three drugs have recently been approved: Gleevec™ (imatinib mesylate) at a starting dose of 400 or 600 mg daily for the treatment of malignant unresectable and/or metastatic gastrointestinal stromal tumors; Mesnex® (mesna) tablets as a prophylactic agent to reduce the incidence of ifosfamide-induced hemorrhagic cystitis, and Zometa® (zoledronic acid) for the treatment of patients with multiple myeloma and for patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy. The recommended dose and schedule is 4 mg infused over 15 minutes every 3-4 weeks. These three drugs represent three different types of drug approval: Gleevec is an accelerated approval and supplemental new drug application (NDA); Mesnex tablets represent an oral formulation of a drug approved 14 years ago as an intravenous formulation, and Zometa represents a standard NDA for a noncytotoxic, supportive-care drug. Information provided includes rationale for drug development, study design, efficacy and safety results, and pertinent literature references.
Clinical Trial Design for Target-Based Therapy
Authors: Fox Elizabeth , Curt Gregory A. , Balis Frank M. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: Differentiate between cytotoxic and molecularly-targeted drug development in terms of drug discovery, mechanism of action, pharmacological effect, and specificity.Define the primary objectives of phase I, II, and III clinical trials of cytotoxic and molecularly targeted anticancer agents.Compare the end points used in clinical trials for cytotoxic agents to the proposed end points for target-based (cytostatic) agents.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Anticancer drug discovery has shifted from an empiric random screening directed approach to a more rational and mechanistic, target-based approach, which reflects our rapidly expanding knowledge of the pathogenesis of a variety of forms of cancer at the molecular level, providing new targets for drug discovery and development. The clinical development of target-based anticancer drugs will require fundamental changes to the traditional clinical trial design and end points that have been used for conventional cytotoxic drugs. In the phase I and II settings, traditional end points (toxicity and response) may not be suitable for more selective, cytostatic target-based agents, and these end points may be replaced by biological or pharmacokinetic end points to define the optimal doses and the therapeutic effects of these drugs on their targets. For phase III trials, measurable clinical benefit will continue to be the primary end point. As our understanding of the complex pathways and networks controlling cell signaling, proliferation, and cell death expands, we must learn how and when to use agents to target specific steps in malignant transformation and proliferation, and we must adapt clinical trial design to test the clinical utility of this promising new class of anticancer drugs.
Phase II Trial of Weekly Vinorelbine and Trastuzumab as First-Line Therapy in Patients with HER2+ Metastatic Breast Cancer
Authors: Jahanzeb Mohammad , Mortimer Joanne E. , Yunus Furhan , Irwin David H. , Speyer James , Koletsky Alan J. , Klein Paula , Sabir Tariq , Kronish Lori 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: Summarize the epidemiology and natural history of HER2+ breast cancer.Differentiate the two primary methods for measuring HER2 in breast cancer patients.Appreciate the rationale for investigating vinorelbine in combination with trastuzumab.Discuss the relative efficacy and safety of trastuzumab and vinorelbine in HER2+ breast cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Purpose. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab.
Patients and Methods. A phase II, open-label trial of intravenous vinorelbine (30 mg/m2 on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2+ metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events.
Results. Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3+ = 82% (18/22) response and IHC 2+ = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity.
Conclusions. Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2+ metastatic breast cancer. Further investigation of this novel regimen is planned.