bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Drugs and Novel Targets for Treatment of Invasive Fungal Infections in Patients with Cancer
Authors: Chiou Christine C. , Groll Andreas H. , Walsh Thomas J. 
Published: August 2004

Abstract
Invasive fungal infections have emerged as important causes of morbidity and mortality in profoundly immunocompromised patients with cancer. Current treatment strategies for these infections are limited by antifungal resistance, toxicity, drug interactions, and expense.
In order to overcome these limitations, new antifungal compounds are being developed, which may improve our therapeutic armamentarium for prevention and treatment of invasive mycoses in high-risk patitnts with neoplastic diseases.
Temozolomide, a Novel Alkylating Agent with Activity in the Central Nervous System, May Improve the Treatment of Advanced Metastatic Melanoma
Authors: Agarwala Sanjiv S. , Kirkwood John M. 
Published: August 2004

Abstract
Temozolomide (TMZ) is the first new chemotherapy agent to be approved for the treatment of high-grade malignant gliomas in more than 20 years. This novel oral alkylating agent has demonstrated promising activity not only in brain tumors, but in a variety of solid tumors, including malignant melanoma. TMZ is 100% bioavailable when taken orally and, because of its small size and lipophilic properties, it is able to cross the blood-brain barrier. Concentrations in the central nervous system are approximately 30% of plasma concentrations. Once it has entered the central nervous system, TMZ can be spontaneously converted to the active metabolite. These pharmacologic properties make it an ideal agent for treating central nervous system malignancies. In patients with advanced metastatic melanoma, brain metastases are a major cause of treatment failure. In this setting, TMZ has been shown to be as effective as dacarbazine, with a similar safety profile. More importantly, there is evidence to suggest that TMZ-treated patients have a lower incidence of central nervous system relapse compared with dacarbazine-treated patients. Therefore, TMZ is actively being investigated for the treatment and prevention of brain metastases in melanoma patients. TMZ may become an important part of treatment regimens for advanced metastatic melanoma.
Communicating Genetic Risk: Pros, Cons, and Counsel
Authors: Penson Richard T. , Seiden Michael V. , Shannon Kristen M. , Lubratovich Marcie L. , Roche Maria , 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 at MGH. 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 encourages 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.
This case is of a woman with a personal, and a strong family history of breast cancer, who considered genetic testing for mutations in the BRCA1 and BRCA2 genes. The details of the case have been altered to protect the patient's anonymity. The patient was very anxious and there was disagreement between her healthcare providers about the potential benefits of genetic testing. The discussion of the case focused on several controversial issues, particularly the ownership of genetic information, and who is responsible for disseminating information to the family members at risk. The difficulties in communicating risk, providing emotional support and coping with the continuing uncertainties about screening and intervention are reviewed with an overview of the molecular biology, inheritance, and epidemiology of the BRCA1 and BRCA2 genes.
Genetic Immunotherapy for Cancer
Authors: Ribas Antoni , Butterfield Lisa H. , Economou James S. 
Published: August 2004

AbstractGenetic immunization refers to treatment strategies where gene transfer methods are used to generate immune responses against cancer. Our growing knowledge of the mechanisms regulating the initiation and maintenance of cytotoxic immune responses has provided the rationale for the design of several genetic immunization strategies. Tumor cells have been gene-modified to express immune stimulatory genes and are then administered as tumor vaccines, in an attempt to overcome tumor cell ignorance by the immune system. With the description of well-characterized tumor antigens, multiple strategies have been proposed mainly aimed at optimal tumor antigen presentation by antigen-presenting cells (APC). Among APC, the dendritic cells have been recognized as the most powerful cells in this class, and have become the target for introducing tumor antigen genes to initiate antitumor immune responses. The detailed knowledge of how the immune system can be activated to specifically recognize tumor antigens, and the mechanisms involved in the control of this immune response, provide the basis for modern genetic immunization strategies for cancer treatment.
Anti-Cancer Drug Discovery and Development in Brazil: Targeted Plant Collection as a Rational Strategy to Acquire Candidate Anti-Cancer Compounds
Authors: Mans Dennis R.A. , Rocha Adriana B. , Schwartsmann Gilberto 
Published: August 2004

AbstractThroughout medical history, plant products have been shown to be valuable sources of novel anti-cancer drugs. Examples are the Vinca alkaloids, the taxanes, and the camptothecins, derived from the Madagscan periwinkle plant Catharantus roseus, the Pacific yew Taxus brevifolia, and the Chinese tree Camptotheca acuminata, respectively. For this reason, the South-American Office for Anti-Cancer Drug Development has implemented a large-scale project of acquisition and testing of compounds isolated from South American medicinal plants. The species are selected on the basis of a potentially useful phytochemical composition by consulting ethnopharmacological, chemosystemic, and ecological information. The collected samples are dried and first extracted with an organic solvent, then with distilled water. These crude extracts are evaluated at a concentration of 50 μg/ml for antiproliferative activity against one cell line. Extracts that significantly inhibit the growth of the cells (≥50%) at relatively low concentrations (≤50 μg/ml) are submitted to the more comprehensive disease-oriented screen of the U.S. National Cancer Institute. In parallel, these samples are further purified by bioassay-guided purification, involving repeated fractionation by diverse chromatography methods. If the active substance is expected to represent a novel structure, it is identified by appropriate chemical techniques, mechanistic studies are performed with a wide diversity of tumor models and laboratory techniques, and efforts are undertaken for the synthesis of potentially more useful analogs.
Role of Taxoids in Head and Neck Cancer
Authors: Schrijvers D. , Vermorken J.B. 
Published: August 2004

Abstract
Docetaxel and paclitaxel represent a new class of cytotoxic agents having both a specific chemical structure and mechanism of action. They act to promote tubulin polymerization and the formation of stable microtubules. The microtubules produced in the presence of taxoids are resistant to disassembly by physiologic stimuli, and cells exposed to these agents exhibit an accumulation of disorganized microtubule arrays. This affects the normal mitotic process and eventually results in cell death.
Both drugs are active as single agents in patients with head and neck cancer with response rates ranging from 20% to 40%. They may be combined with other cytotoxic agents, radiotherapy, or both. A review is given of the presently available data.
High-Dose Rate Brachytherapy of Bronchial Cancer: Treatment Optimization Using Three Schemes of Therapy
Authors: Muto Paolo , Ravo Vincenzo , Panelli Giancarlo , Liguori Gaetano , Fraioli Gaetano 
Published: August 2004

Abstract
Purpose. Our aim is to demonstrate that a fractionated high-dose rate endobronchial brachytherapy (HDRBT) treatment is tolerable for patients with advanced (IIIA-IIIB) non-small cell lung cancer and gives an improvement of symptoms.
Patients and Methods. From January 1992 to July 1997, we treated 320 patients with external beam radiotherapy (EBRT) and concomitant HDRBT with Ir192. Eighty-four patients received 10 Gy in one fraction from January 1992 to March 1993 (Group A); 47 patients received two fractions of 7 Gy each from April 1993 to December 1993 (Group B), and 189 patients received three fractions of 5 Gy each from January 1994 to July 1997 (Group C).
Results. Mean survival from diagnosis is 11.1 months and mean survival from last HDRBT is 9.7 months. The symptomatic response rate is 90% for dyspnea, 82% for cough, 94% for hemoptysis and 90% for obstructive pneumonia. Performance status was improved in 70% of patients. Follow-up is in the range of 5-36 months with 280/320 evaluable patients (87.5%) (40 patients were lost to follow-up). For the patients treated with three fractions of HDRBT plus EBRT, a smaller number of side effects occurred while relief from symptoms linked to bronchial obstruction and survival was similar for the three groups.
Conclusions. A three-fraction brachytherapy results in fewer side effects, such as bronchial fibrosis with or without stenosis, while survival and symptomatic relief are similar in the three groups treated.
Management of Cancer in the Older Person: A Practical Approach
Authors: Balducci Lodovico , Extermann Martine 
Published: August 2004

Abstract
The management of cancer in the older aged person is an increasingly common problem. The questions arising from this problem are: Is the patient going to die with cancer or of cancer? Is the patient able to tolerate the stress of antineoplastic therapy? Is the treatment producing more benefits than harm?
This article explores a practical, albeit evolving, approach to these questions including a multidimensional assessment of the older person and simple pharmacologic interventions that may ameliorate the toxicity of antineoplastic agents. Age may be construed as a progressive loss of stress tolerance, due to decline in functional reserve of multiple organ systems, high prevalence of comorbid conditions, limited socioeconomic support, reduced cognition, and higher prevalence of depression. Aging is highly individualized: chronologic age may not reflect the functional reserve and life expectancy of an individual. A comprehensive geriatric assessment (CGA) best accounts for the diversities in the geriatric population. The advantages of the CGA include: Recognition of potentially treatable conditions such as depression or malnutrition, that may lessen the tolerance of cancer treatment and be reversed with proper intervention;Assessment of individual functional reserve;Gross estimate of individual life expectancy; andAdoption of a common language to classify older cancer patients.
The CGA allows the practitioner to recognize at least three stages of aging: People who are functionally independent and without comorbidity, who are candidates for any form of standard cancer treatment, with the possible exception of bone marrow transplant.People who are frail (dependence in one or more activities of daily living, three or more comorbid conditions, one or more geriatric syndromes), who are a candidate only for palliative treatment; andPeople in between, who may benefit from some special pharmacological approach, such as reduction in the initial dose of chemotherapy with subsequent does escalations.
The pharmacological changes of age include decreased renal excretion of drugs and increased susceptibility to myelosuppression, mucositis, cardiotoxicity and neurotoxicity. Based on these findings, the proposal was made that all persons aged 70 and older, treated with cytotoxic chemotherapy of dose intensity comparable to CHOP, receive prophylactic growth factor treatment, and that the hemoglobin of these patients be maintained ≥12 gm/dl.
The Prednisone Dosage in the CHOP Chemotherapy Regimen for Non-Hodgkin's Lymphomas (NHL): Is There a Standard?
Authors: Moreno Alvaro , Colon-Otero Gerardo , Solberg Lawrence A. 
Published: August 2004

Abstract
Purpose. Discrepancies in the quoted prednisone dosages in the regimens reported as the only standard CHOP regimen stimulated our interest in reviewing the medical literature regarding this issue and to assess whether practicing hematologists and oncologists in the U.S. are aware of the different dose schedules of prednisone in the published CHOP programs.
Methods. Sixteen textbooks and chemotherapy reference books were reviewed. A MEDLINE search of English-language articles published between January 1970 and December 1998 was performed. An eight-point questionnaire was sent via e-mail with responses obtained from 421 hematology/oncology physicians in the U.S..
Results. Sixteen textbooks and chemotherapy reference books reviewed quoted only one prednisone dosage as part of the standard CHOP regimen; the prednisone dosages quoted as standard varied between publications. More than 4,000 eligible non-Hodgkin's lymphoma patients have been treated with the CHOP chemotherapy as part of 43 different clinical trials reviewed. The dosages of prednisone and prednisolone used varied among six different levels. Thirty percent (127/421) of practicing U.S. physicians were not aware of the existence of more than one prednisone dose schedule as part of the CHOP regimen. The three most frequently used dosages are 100 mg/days 1-5 (67%), 100 mg/m2/days 1-5 (17%), and 60 mg/m2/days 1-5 (13%).
Conclusions. Discrepancies in steroid dosages used as part of the reported standard CHOP regimens are common and not well recognized in the medical literature nor by practicing U.S. hematologists/oncologists. Based on this study, a prednisone dose of 100 mg/day for five days should be considered the standard dose.
The Consequences of Diarrhea Occurring During Chemotherapy for Colorectal Cancer: A Retrospective Study
Authors: Arbuckle R.B. , Huber S.L. , Zacker C. 
Published: August 2004

Abstract
Purpose. Diarrhea is one of the dose-limiting toxicities associated with chemotherapy agents in treatment regimens for colorectal cancer. The objectives of this study were to analyze the impact of all grades of diarrhea on clinical decisions for patients receiving treatment for colorectal cancer by characterizing the diarrhea that occurred, quantifying changes in chemotherapy treatment, identifying methods to treat diarrhea, and determining the economic impact.
Patients and Methods. We retrospectively reviewed the treatment of 100 consecutive patients with colorectal cancer who experienced diarrhea during the course of chemotherapy. The diarrhea was documented in the progress notes and graded according to National Cancer Institute Common Toxicity Criteria. Changes in chemotherapy treatment and resource utilization associated with diarrhea were recorded.
Results. The 100 patients received 673 chemotherapy cycles, of which 45% ± 2% were associated with diarrhea. Approximately 52% of patients experienced diarrhea of grades 3 or 4, and 56 patients underwent 66 modifications in their chemotherapy treatment, such as dose reductions (22), delays in therapy (8), discontinuations of therapy (15), or multiple changes (11). Thirty-seven patients consumed resources beyond oral antidiarrheals to control diarrhea: 14 patients received emergency outpatient treatment, 23 patients were hospitalized, 21 patients received intravenous fluids, and one death due to dehydration was reported.
Discussion and Conclusion. Diarrhea was a significant consequence of colorectal chemotherapy, with the majority of patients experiencing grades 3 or 4 diarrhea and 56% of all patients also modifying their chemotherapy treatment. Even mild diarrhea of grades 1 and 2 was associated with changes in treatment in 11% of patients; thus, diarrhea of all grades should be recognized and treated appropriately to maintain full-dose chemotherapy.
The Role of Behavioral and Psychosocial Science in Reducing Cancer Morbidity and Mortality
Authors: Burish Thomas G. 
Published: August 2004

Abstract
Behavioral and psychosocial science has the potential to contribute much to the overall effort to reduce cancer morbidity and mortality and to improve the quality of life for cancer patients and their families. However, for a variety of reasons, including a lack of sustained funding for research and training and a lack of confidence by some in the potential payoff for investments in the area, this potential has not only not been realized but also not been adequately explored. A special subcommittee of “The March” Research Task Force studied research in this area and issued a report making several recommendations for future funding for psychosocial and behavioral research in cancer. This article reports those recommendations and the reasons the committee supported them.
Highlights in Ovarian Cancer
Authors: Seiden Michael 
Published: August 2004

Abstract
The ovarian cancer presentations at the 2000 ASCO meeting did not yield any major paradigm shifts in the treatment of women with epithelial ovarian cancer. Emphasis at this year's meeting focused on the potential incorporation of drugs such as topotecan, oxaliplatin, doxil, and gemcitabine into the initial treatment strategies of women with advanced ovarian cancer. These studies included the introduction of several active and tolerable regimens that are potentially worthy of direct comparison to the carboplatin and paclitaxel combination. In the woman with recurrent or persistent ovarian cancer there was a greater focus on phase III studies directly comparing various chemotherapy strategies in the treatment of women with recurrent disease. This included the comparisons of single-versus two-drug salvage regimens, alternate salvage schedules, and direct comparison of agents active in taxane- and platinum-resistant disease. Finally, several early studies of novel non-chemotherapeutic strategies were presented.
Hematologic Malignancies: Selected Abstracts and Commentary
Authors: Grossbard Michael L. 
Published: August 2004

Abstract
ASCO 2000 did not offer revolutionary new advances in the treatment of hematologic malignancies. However, reports at the meeting built incrementally on gains established over the past several years. The meeting continued to highlight advances in the targeted therapy of hematologic malignancies. Excitement abounds regarding the clinical development of STI 571, a rationally designed tyrosine kinase inhibitor, for the treatment of chronic myelogenous leukemia. Studies further defined the role monoclonal antibody treatment for non-Hodgkin's lymphoma and more mature data were presented on both unconjugated antibody therapy and radioimmunoconjugates. In disease detection, important data were presented to clarify the role of positron emission tomography scans in the staging and follow-up of lymphoid malignancies. The following review summarizes key abstracts presented at the 2000 ASCO meeting and will elaborate on the implications of these findings for disease management.
Breast Cancer Update
Authors: Kuter Irene 
Published: August 2004

Abstract
The large number of excellent presentations on breast cancer at this year's ASCO meeting reflects the enormous interest in clinical trials of this common disease. In the reports of adjuvant hormonal therapy, the most interesting included Abstract 273 by Boccardo et al., who reported that postmenopausal women with estrogen receptor positive (ER+) cancers who had already completed three years of tamoxifen experienced better overall survival if treated with two years of subsequent aminoglutethimide (a first-generation aromatase inhibitor) rather than another two years of tamoxifen. This whets our appetite for studies currently under way to define the role of third-generation aromatase inhibitors in the adjuvant setting. A report by Fisher from the National Surgical Adjuvant Breast and Bowel Project B-23 study (Abstract 277) provided confirmation of what is rapidly becoming accepted, that the addition of tamoxifen to chemotherapy does not benefit breast cancer patients with negative lymph nodes who have ER– cancers. In premenopausal women, another report of the benefit of hormonal therapy, this time by the French Adjuvant Study Group using complete hormonal blockade with a luteinizing hormone-releasing hormone agonist and tamoxifen (Abstract 279) showed that hormonal therapy can be at least as good as, if not better, than six cycles of 5-fluorouracil 500 mg/m2, epirubicin 50 mg/m2, cyclophosphamide 500 mg/m2 in terms of disease-free survival and overall survival.
Among the papers on adjuvant chemotherapy, a controversial paper from the German Adjuvant Breast Cancer Group reported that three cycles of CMF (a dose-intense regimen with all three drugs being given on days 1 and 8) were as good as six cycles (Abstract 283). Another report, from the International Breast Cancer Study Group, raised the controversial question of whether there really is much added benefit from the addition of chemotherapy to tamoxifen in postmenopausal women with negative lymph nodes if their tumors have ERs (Abstract 281). A second study (the first was the CALGB study reported at ASCO in 1998) showing a benefit to the addition of Taxol to an anthracycline-based adjuvant regimen, was reported from the M.D. Anderson Cancer Center (Abstract 285), giving further impetus to the inclusion of Taxol in standard adjuvant treatment.
Finally, there were a number of interesting presentations on HER-2. Reported here are three of these, all addressing the effect of HER-2 overexpression on the response to hormonal therapy. Taken together, they uphold the emerging concern that women with ER+ cancers may not benefit significantly from endocrine treatment if the tumors also overexpress HER-2. Observations such as these will afford us the ability to predict more accurately which women will benefit from specific treatments.
Prophylactic Cranial Irradiation in Small-Cell Lung Cancer
Authors: Yang Gary Y. , Matthews Richard H. 
Published: August 2004

Abstract
Prophylactic cranial irradiation is now known to improve survival to a significant degree in small-cell lung cancer (SCLC) patients; this is in addition to its established role in preventing the disabling symptoms of brain metastases. New information indicates that it confers a survival benefit for limited or extensive stage SCLC patients gaining a complete response in the chest. A review of causes of cerebral dysfunction as a complication indicates that such problems can be due to suboptimal radiation fractionation, chemotherapy, or an inappropriate combination of prophylactic brain irradiation with chemotherapy. Optimum treatment with prophylactic brain irradiation has been shown not to cause adverse effects with detailed psychometric testing. Several additional sources of information can be drawn together to suggest a dose-response pattern for prophylactic brain irradiation, leading to the recommendation that a dose of 25-36 Gy is optimal, delivered in 2-3 Gy daily fractions after the completion of chest irradiation and chemotherapy. This will be better defined in future clinical trials.