bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pemetrexed Disodium: A Novel Antifolate Clinically Active Against Multiple Solid Tumors
Authors: Hanauske Axel-R. , Chen Victor , Paoletti Paolo , Niyikiza Clet 
Published: August 2004

Abstract
Pemetrexed disodium (ALIMTA®, “pemetrexed”) is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck. Pemetrexed inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. As a single agent, pemetrexed exhibits a moderate toxicity profile at a dose of 500 mg/m2 by 10-minute infusion once every 21 days with myelosuppression being the dose-limiting toxicity. Folic acid added to the diet in preclinical studies reduced toxicities while maintaining antitumor activity. Based on this observation and clinical toxicities, folic acid and vitamin B12 dietary supplementation has been recently introduced into all ongoing trials. Studies combining pemetrexed with other active chemotherapeutic agents demonstrate that these combination therapies may become important treatment regimens in a variety of cancer types. Currently, pemetrexed phase III trials are ongoing in mesothelioma and non-small cell lung cancer with future trials planned to explore this unique multitargeted antifolate.
Adjuvant Therapy of Primary Breast Cancer: A Review of Key Findings from the 7th International Conference, St. Gallen, February 2001
Authors: Aapro Matti S. 
Published: August 2004

Abstract
Breast cancer research has developed at a rapid pace over the last decades. Recent discoveries promise to provide individualized treatment options, increased long-term survival for women with breast cancer, and the possibility of moving toward curative intent in the treatment of advanced breast cancer. Age, race, tumor size, histological tumor type, axillary nodal status, standardized pathological grade, and hormone-receptor status are accepted as established prognostic and/or predictive factors for selection of systemic adjuvant treatment of breast cancer. The role of other promising new factors, such as p53 mutations, HER-2 status, plasminogen activator system, histological evidence of vascular invasion, and quantitative parameters of angiogenesis will be determined in ongoing prospective studies. Currently, 5 years' treatment with adjuvant tamoxifen in women with hormone-positive receptor status, is regarded as the optimal duration of treatment. Long-term follow-up on the randomized trials will determine the added benefit of treatment beyond 5 years. Ovarian ablation has shown a reduction in recurrence and death, and the exact role and extent of adjuvant chemotherapy in premenopausal women with hormone-responsive tumors is under discussion. Combination hormonal and chemo-hormonal therapies are also being evaluated. There are no convincing data on the survival impact of tamoxifen as a preventative therapy for breast cancer: longer-term follow-up is required, and the planned meta-analyses in 2005 should help shed light on this issue. Statistically significant benefits have been observed with adjuvant chemotherapy (particularly with anthracycline-containing regimens in premenopausal women) versus no adjuvant chemotherapy. The optimal length of adjuvant anthracycline/cyclophosphamide (AC) regimens needs further evaluation as do randomized comparisons of AC to cyclophosphamide/ doxorubicin/5-fluorouracil (5-FU) and cyclophosphamide/epirubicin/5-FU. Although taxanes promise to provide an additive benefit to adjuvant chemotherapy regimens, the Cancer and Leukemia Group B 9344 and the National Surgical Adjuvant Breast and Bowel Project B-28 studies evaluating paclitaxel in the adjuvant setting have not yet demonstrated statistically significant benefits on disease-free survival and overall survival. In the year 2000, all adjuvant therapy studies conducted by the Co-operative Groups in both node-negative and node-positive disease involve a taxane. High-dose chemotherapy evaluations are still ongoing. The numerous prospective adjuvant therapy trials (hormonal; selective estrogen-receptor modulators; aromatase inhibitors; chemotherapy, involving anthracyclines/taxanes/platinum/trastuzumab; biological factors; elderly women (&gt;70 years); high-risk patients; radiotherapy in 1-3 positive lymph nodes), and neoadjuvant studies might further define the chances to enhance cure rates in the treatment of primary breast cancer.
Lung Cancer
Authors: Evans Tracey L. , Lynch Thomas J. 
Published: August 2004

Abstract
Is any one combination therapy for metastatic non-small cell lung cancer (NSCLC) superior to other regimens for metastatic NSCLC? The answer is “probably no.” More than 4,000 patients with advanced NSCLC participated in randomized trials presented at the 37th Annual Meeting of the American Society of Clinical Oncology. TAX326 was the only study in which the investigational arm (cisplatin/docetaxel) showed a statistically significant difference in survival compared with the reference standard (cisplatin/vinorelbine). We did learn, however, that what we administer may make some difference: cisplatin might be superior to carboplatin, and patients treated with nonplatinum chemotherapy regimens have a trend toward poorer survival than those who receive platinum doublets. Although there is still no clear best regimen for advanced NSCLC, we may now know how much chemotherapy to give: a randomized study presented found that four cycles produces as much survival benefit as treating until progression. The most significant abstracts presented at this year's lung cancer session involved the use of novel agents with unique mechanisms of action. The median survival in the large, randomized trials of chemotherapy in advanced NSCLC remains a bleak 9 months. ISIS 3521, an antisense oligonucleotide that targets protein kinase C, was found to produce a near doubling of survival when combined with carboplatin and paclitaxel. OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, was shown to have impressive single agent activity in the second-line treatment of lung cancer. The future of lung cancer therapy will involve combining these novel agents with active chemotherapy regimens in an effort to improve outcome.
While we appear to have reached a plateau in what we can accomplish with various combinations of cytotoxic chemotherapy in metastatic NSCLC, in locally-advanced disease new chemotherapy combinations can achieve remarkable results when combined with radiation therapy. The Southwest Oncology Group presented unprecedented phase II data on the use of cisplatin and etoposide with concurrent radiation therapy followed by consolidation docetaxel in patients with stage IIIB NSCLC.
Matrix Metalloproteinase Inhibitors: Current Developments and Future Perspectives
Authors: Hoekstra R. , Eskens F.A.L.M. , Verweij J. 
Published: August 2004

Abstract
Malignant tumors are characterized by invasive growth and metastasis. To facilitate this invasive behavior, the enzymatic breakdown of the extracellular matrix (ECM) is a prerequisite. Many human tumors are characterized by locally increased concentrations of matrix metalloproteinases (MMPs), enzymes that are able to degrade this ECM. A vast number of matrix metalloproteinase inhibitors (MMPIs) have been developed in recent years and after extensive preclinical testing, the results of the first clinical studies with several of these compounds have recently been presented. In this review we will describe some of the basic concepts of the degradation of the ECM, with special emphasis on the role of MMPs in the progression of cancer. Furthermore we will review the results of preclinical and clinical studies with MMPIs and discuss their future perspective.
Changes in Finances, Insurance, Employment, and Lifestyle Among Persons Diagnosed with Hairy Cell Leukemia
Authors: Hounshell Jennie , Tomori Cecilia , Newlin Rebecca , Knox Kirstin , Rundhaugen Lynn , Tallman Martin , Bennett Charles 
Published: August 2004

Abstract
Background. While being cured of cancer generally leads to a life expectancy similar to that of the general population, the extent to which other aspects of life are affected is unknown. To address these concerns, patients with hairy cell leukemia, a cancer with a very high cure rate, were queried about employment, insurance, finances, and lifestyle during and following their treatment.
Methods. Study participants (n = 31) ranging in age from 24 to 73 years at the time of diagnosis (median, 49 years) were surveyed regarding changes in health and life insurance, employment, out-of-pocket medical costs, exercise, diet, and use of mental and alternative health services that occurred during or following hairy cell leukemia treatment.
Results. Following a diagnosis of hairy cell leukemia, 61.3% of the respondents paid for some aspect of medical care in spite of having health insurance coverage at the time of diagnosis. Four respondents (12.9%) could not obtain health insurance following treatment, and the occupational choices of several individuals or their spouses were based in large part on a desire to obtain or maintain comprehensive health insurance. Of the 13 individuals who attempted to purchase life insurance, 10 had difficulty obtaining a policy or were denied coverage. Lifestyle changes were noted by 40% to 60% of respondents, and included reports of more frequent exercise, adoption of a healthier diet, and having a greater appreciation for life, loved ones, and physical health.
Conclusions. While hairy cell leukemia is a highly curable malignancy, cancer survivors' lives and lifestyles are altered substantially after receiving treatment for the illness.
Evaluating the Total Costs of Chemotherapy-Induced Toxicity: Results from a Pilot Study with Ovarian Cancer Patients
Authors: Calhoun Elizabeth A. , Chang Chih-Hung , Welshman Emily E. , Fishman David A. , Lurain John R. , Bennett Charles L. 
Published: August 2004

Abstract
Purpose. While chemotherapy-related toxicities affect cancer patients' activities of daily living and result in large expenditures of medical care for treatment, few studies have assessed the out-of-pocket and indirect costs incurred by patients who experience toxicity. The objective of this study was to evaluate the feasibility of obtaining detailed and comprehensive cost information from patients who experienced neutropenia, thrombocytopenia, or neurotoxicity during treatment.
Methods. Ovarian cancer patients who experienced chemotherapy-associated hematologic or neurologic toxicities were asked to record detailed information about hospitalization, laboratories, physician visits, phone calls, home visits, medication, medical devices, lost productivity, and caregivers. Resource estimates were converted into cost units, with direct medical cost estimates based on hospital cost-accounting data and indirect costs (i.e., productivity loss) on modified labor force, employment, and earnings data.
Results. Direct medical costs were highest for neutropenia (mean of $7,546/episode), intermediate for thrombocytopenia (mean of $3,268/episode), and lowest for neurotoxicity (mean of $688/episode). Indirect costs relating to patient and caregiver work loss and payments for caregiver support were substantial, accounting for $4,220, $3,834, and $4,282 for patients who developed neurotoxicity, neutropenia, and thrombocytopenia, respectively. The total costs of chemotherapy-related neurotoxicity, neutropenia, and thrombocytopenia were $4,908, $11,830, and $7,550.
Conclusion. Our study has shown that, with the assistance of patients who are experiencing toxicity, estimation of the total costs of cancer-related toxicities is feasible. Indirect costs, while not included in prior estimates of the costs of toxicity studies, accounted for 34% to 86% of the total costs of cancer supportive care.
New Strategies for Prophylactic Platelet Transfusion in Patients with Hematologic Diseases
Authors: Wandt Hannes , Ehninger Gerhard , Gallmeier Walter Michael 
Published: August 2004

Abstract
There is an increasing demand for platelet transfusions due to intensive chemotherapy and blood stem cell or bone marrow transplantation for the treatment of hematologic and oncologic diseases. There has been a long-lasting debate over whether the traditional threshold for prophylactic platelet transfusion of 20,000/μl is really necessary to prevent hemorrhagic complications. During the last 10 years several studies with more than 1,000 patients together have proven the safety of a platelet transfusion trigger of 10,000/μl or even lower when patients are clinically stable without active bleeding. This experience has been mostly gathered in patients with acute leukemia. But this stringent platelet transfusion policy can be used also after blood stem cell and bone marrow transplantation. In stable patients with aplastic anemia and myelodysplasia, prophylactic transfusions should be replaced in most patients by a therapeutic transfusion strategy. Such restrictive platelet transfusion strategies decrease the risk of infectious disease transmission, immunization, and febrile transfusion reactions. Besides reduced hospital visits and a shorter hospital stay for the patients, the costs for platelet transfusions are lowered by 20%-30% compared with traditional transfusion strategies. The decision to administer platelet transfusions should incorporate individual clinical characteristics of the patients and not simply be a reflexive reaction to the platelet count. Further clinical studies are needed to answer the still open question of whether patients with acute leukemia should also be transfused therapeutically rather than prophylactically when they are in stable condition without signs of active bleeding.
The NCI-Ireland Consortium: A Unique International Partnership in Cancer Care
Authors: Johnston Patrick G. , Daly Peter A. 
Published: August 2004

Abstract
The Ireland-Northern Ireland-National Cancer Institute Cancer Consortium was launched in October of 1999, at a conference in Belfast, Northern Ireland, for the development of cancer programs in Ireland and Northern Ireland, where cancer is a significant cause of mortality and morbidity.
Cancer services there have undergone major restructuring as a result of several government reports. Specifically, the National Strategy Document for Cancer proposed that cancer treatment services should be centered around primary care services, regional services, and a national coordinating structure where supra-regional centers would deliver specialist surgery, medical and radiation oncology, rehabilitation, and specialist palliative care. Therefore, this was an opportune time to bring the National Cancer Institute (NCI) on board in a determined effort to redevelop and significantly improve services and outcomes for cancer patients throughout the island.
During the NCI All Ireland Cancer Consortium, initial major goals were established as follows: A) To share best available technology and enhance clinical research; B) conduct joint clinical research studies involving people from all jurisdictions; C) sponsor formal training exchanges for Irish and American scholars in cancer programs in partner institutions; D) implement the use of teleconferencing, telesynergy, and other information technology capabilities to facilitate education, and E) consolidate the Cancer Registries of Ireland and Northern Ireland and learn more about cancer incidence and trends on the entire island. In the past year, significant advances have been made in all these areas.
Plans are already under way for the second NCI All Ireland Cancer Conference which will be held in late 2002 and feature speakers from Ireland, Northern Ireland, the U.S., and other areas. It will be open to all oncologists, researchers, nurses, students, and other health care professionals interested in learning and enhancing cancer care and research.
Complementary, Alternative, Integrative, or Unconventional Medicine?
Authors: Penson Richard T. , Castro Cesar M. , Seiden Michael V. , Chabner Bruce A. , Lynch Thomas J. 
Published: August 2004

Abstract
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), 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.
Interest in complementary and alternative medicine (CAM) has grown exponentially in the past decade, fueled by Internet marketing, dissatisfaction with mainstream medicine, and a desire for patients to be actively involved in their health care. There is a large discordance between physician estimates and reported prevalence of CAM use. Many patients do not disclose their practices mainly because they believe CAM falls outside the rubric of conventional medicine or because physicians do not ask. Concern about drug interactions and adverse effects are compounded by a lack of Food and Drug Administration regulation. Physicians need to be informed about CAM and be attuned to the psychosocial needs of patients.
The Development of Camptothecin Analogs in Childhood Cancers
Authors: Bomgaars Lisa , Berg Stacey L. , Blaney Susan M. 
Published: August 2004

Abstract
Camptothecin analogs, agents that target the intranuclear enzyme topoisomerase I, represent a promising new class of anticancer drugs for the treatment of childhood cancer. In preclinical studies, camptothecins, such as topotecan and irinotecan, are highly active against a variety of pediatric malignancies including neuroblastomas, rhabdomyosarcomas, gliomas, and medulloblastomas. In this paper, we review the status of completed and ongoing clinical trials and pharmacokinetic studies of camptothecin analogs in children. These and future planned studies of this novel class of cytotoxic agents are critical to defining the ultimate role of topoisomerase I poisons in the treatment of childhood cancer.
Selected Novel Anticancer Treatments Targeting Cell Signaling Proteins
Authors: Elsayed Yusri A. , Sausville Edward A. 
Published: August 2004

AbstractEmpirical approaches to discovery of anticancer drugs and cancer treatment have made limited progress in the cure of cancer in the last several decades. Recent advances in technology and expanded knowledge of the molecular basis of tumorigenesis and metastasis have provided unique opportunities to design novel compounds that rationally target the abnormal molecular and biochemical signals leading to cancer. Several such novel agents have completed advanced stages in clinical development. The excellent clinical results achieved by some of these compounds are creating new paradigms in management of patients with neoplastic diseases. Clinical development of these agents also raises challenges to the traditional methods of drug evaluation and measurement of efficacy.
Combination Endocrine Therapy in the Management of Breast Cancer
Authors: Boehnke Michaud Laura , Jones Kellie L. , Buzdar Aman U. 
Published: August 2004

Abstract
Combination endocrine therapy has long been sought after as a means to better treat breast cancer. Agents that suppress estrogen production are given with agents that suppress estrogenic activity at the cellular level. Historically, these combinations have resulted in initial improvements in response rates, but relapse-free and overall survival were not significantly improved. Also, the increased toxicity seen with these regimens was limiting. New endocrine therapies with more potent activity and less toxicity have led to a resurgence of this idea in the management of breast cancer. Complete estrogen blockade has been compared with single-agent treatments in many different settings. The endocrine effects of this type of therapy are intriguing, but apparently do not readily predict a clinical advantage. The combination of an aromatase inhibitor and an antiestrogen, despite pharmacokinetic interactions, may prove to be beneficial. Results from ongoing trials are eagerly awaited to further address this question in postmenopausal breast cancer patients. For premenopausal breast cancer patients the options are more complex. Clinical outcomes with leutinizing hormone releasing hormone (LHRH) agonists plus aromatase inhibitors are limited to very small phase II studies and are not clearly superior to single-agent therapy. Clinical data in the metastatic setting with premenopausal patients favor the use of an LHRH agonist with tamoxifen over the use of an LHRH agonist alone. However, a similar comparison with tamoxifen alone is lacking with only one trial including this as a treatment arm. Adjuvant therapy with this combined endocrine approach (LHRH agonist plus antiestrogen) has been more extensively studied, but lacks crucial comparisons necessary for making complex treatment decisions. Hopefully, through investigative diligence and ingenuity this issue can be adequately understood. However, many exciting new agents are on the horizon that offer hope to further advance the progress made to date although further confounding the questions already answered.