Abstract:
:Although originally developed as an antitumor agent in the 1970s, dexrazoxane (DEX) is currently used as a cardioprotective agent in combination with doxorubicin (DOX). Due to concerns about anthracycline-induced cardiotoxicity at higher cumulative doses, many investigators have chosen to administer DOX by prolonged infusion. Therefore, with the ultimate goal of combining infusional DEX and DOX, we performed a phase I study of intravenous DEX alone as a 96-hour infusion. Surprisingly, the maximum tolerated dose of DEX identified in this study was 10- to 15-fold lower than previously determined using different schedules of administration. Results of pharmacokinetic studies in support of the trial have found that steady-state DEX plasma concentrations in the range of 4 to 5 micromol/L can be achieved safely. Because previous experiments have explored the ability of DEX to inhibit the catalytic activity topoisomerase II at low micromolar concentrations and due to a lack of in vitro cytotoxicity data for long-term exposures, we performed further laboratory studies to provide a context for our pharmacokinetic findings. As a result of these correlative studies, we have found that prolonged exposures to DEX are cytotoxic to human leukemic cells at concentrations that are clinically achievable.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Synold TW,Tetef ML,Doroshow JHsubject
Has Abstractpub_date
1998-08-01 00:00:00pages
93-9issue
4 Suppl 10eissn
0093-7754issn
1532-8708journal_volume
25pub_type
临床试验,杂志文章abstract::Activation of mammalian target of rapamycin (mTOR) signaling occurs in a wide variety of human tumors and can lead to increased susceptibility to mTOR inhibitors. Temsirolimus, a novel analog of rapamycin, has shown promising preclinical and early clinical anti-tumor activity in various solid and hematologic tumor typ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2009.10.010
更新日期:2009-12-01 00:00:00
abstract::Improving local tumor control is a goal of modern radiotherapy that will directly impact a majority of cancer patients. Numerous attempts to develop radiosensitizing agents have, however, met with limited clinical success. Recent advances in gene therapeutic approaches have allowed researchers to combine gene therapy ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1997-12-01 00:00:00
abstract::The outcomes in young adults aged 20-39 with sarcoma tend to be inferior compared to those in children and adolescents. There are differences in sarcoma histotype distribution with age, such that pediatric-type tumors predominate in the 20- to 25-year-old group while more adult-type sarcomas occur in those aged 35-39 ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2009.03.006
更新日期:2009-06-01 00:00:00
abstract::Capecitabine is an orally administered fluoropyrimidine carbamate that is preferentially converted to 5-fluorouracil in tumors relative to normal tissue. Three different dosing regimens were investigated in phase I studies: continuous monotherapy, intermittent monotherapy, and intermittent therapy supplemented with le...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1016/s0093-7754(01)90251-9
更新日期:2001-02-01 00:00:00
abstract::Approximately one third of patients diagnosed with early-stage colon cancer will present with lymph node involvement (stage III) and about one quarter with transmural bowel wall invasion but negative lymph nodes (stage II). Adjuvant chemotherapy targets micrometastatic disease to improve disease-free (DFS) and overall...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2011.05.005
更新日期:2011-08-01 00:00:00
abstract::In the United States there are approximately 100,000 women living with metastatic breast cancer. Bone is the most common site of breast cancer metastases and it is estimated that up to 85% of patients dying from this disease have developed osseous involvement. Skeletal metastases are often associated with dangerous an...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2001.25445
更新日期:2001-08-01 00:00:00
abstract::This article reviews the associations of cancer with rheumatic diseases. Recent epidemiologic data linking the autoimmune connective tissue diseases with malignancy will be emphasized. Reports linking the occurrence of malignancy with rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathy...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1997-06-01 00:00:00
abstract::Although chemotherapeutic regimens remain limited in activity against non-small cell lung cancer, some novel cytotoxic agents and radiotherapy techniques, alone or in combination, have shown promising advances. Numerous clinical trials have demonstrated increases in overall response rates, and some agents have shown a...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-04-01 00:00:00
abstract::Blast crisis terminates the life of the majority (approximately 80%) of patients with CML. The time of its onset appears to be a random phenomenon, varying from a probable coincidence occurrence with the onset of CML to more than a decade after onset of the chronic phase. In most patients the diagnosis is obvious as v...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::As a result of the increasing effectiveness of cancer screening and preventive interventions, ethical issues, as well as legal liabilities, are increasingly associated with cancer genetic testing. These issues include the possible "duty to warn" relatives of inherited cancer risk, the appropriateness of testing of chi...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.07.007
更新日期:2007-10-01 00:00:00
abstract::The combination of paclitaxel and carboplatin is now established as the standard first-line chemotherapy regimen for advanced ovarian cancer. Ways in which this standard therapy can be further improved are being investigated, and several approaches have been taken. One approach is to integrate a different cytotoxic ag...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2006.03.015
更新日期:2006-04-01 00:00:00
abstract::The supplanting of radical mastectomy by simple mastectomy and then by lumpectomy plus radiation, the use of adjuvant therapy to alter the natural course of breast and colorectal cancer, the use of tamoxifen for the prevention of breast cancer, and the dramatic improvement in survival demonstrated with the use of the ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2008.07.005
更新日期:2008-10-01 00:00:00
abstract::Cytarabine and hydroxyurea in combination are known to inhibit the DNA excision repair system. Given this system is responsible for repair of cisplatin-DNA adducts, we hypothesized that combining cytarabine, hydroxyurea, and cisplatin in an appropriate schedule might inhibit adduct repair, increase the number of DNA l...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::Cisplatin is recognized as an active chemotherapeutic agent in a broad variety of human tumors. The severe emetic effects of cisplatin, however, result in both acute and delayed emesis syndromes causing considerable morbidity. Over the last decade, the standard of therapy for control of cisplatin-induced emesis has be...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1991-02-01 00:00:00
abstract::The ability to predict the biological behavior of breast tumors can allow selection of the optimum treatment and follow-up strategies. Conventionally, tumor size, lymph node metastases, and histopathologic features have been used to determine the risk of systemic relapse. The discovery of a number of specific genetic ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-08-01 00:00:00
abstract::This phase I study was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with standard doses of cisplatin and etoposide for patients with untreated, extensive-stage small cell lung cancer. Secondary objectives were to determine the toxicities, response ...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::Inflammatory breast cancer (IBC) is an extremely aggressive disease that progresses rapidly and carries a very grim prognosis. It is characterized by erythema, rapid enlargement of the breast, skin ridging, and a characteristic peau d'orange appearance of the skin secondary to dermal lymphatic tumor involvement. Altho...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.11.010
更新日期:2008-02-01 00:00:00
abstract::Colorectal cancer is an ideal model in which to study malignant progression from the molecular-genetic perspective because different stages of the same malignancy coexist within each patient. Approximately 75% of colorectal cancer cases are sporadic and the remaining are familial disease, yet genetic mutations that ha...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2006.10.003
更新日期:2006-12-01 00:00:00
abstract::The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7-week total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with standard curative radiotherapy (RT) for pre...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC) (11% complete response [CR], 59% CR plus partial response [PR]). Combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease (LD), with 52% CRs. The ...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1992-02-01 00:00:00
abstract::In vitro data suggest a synergistic antiproliferative effect of different cytokines. In four clinical studies chronic myelogenous leukemia (CML) patients were treated with interferon (IFN)-alpha alone or IFN-alpha combined with either low-dose IFN-gamma or tumor necrosis factor (TNF)-alpha. The best response was achie...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1992-04-01 00:00:00
abstract::Monoclonal antibodies (mAbs) and their directly derived cell-based application known as chimeric antigen receptors (CARs) ensue from the need to develop novel therapeutic strategies that retain high anti-tumor activity, but carry reduced toxicity compared to conventional chemo- and radiotherapies. In this concise revi...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2014.08.005
更新日期:2014-10-01 00:00:00
abstract::Navelbine (NVB) or 5' nor-anhydro-vinblastine was shown to present a broader antitumor activity and to induce fewer side effects than vinblastine (VBL) or vincristine (VCR). The possible mechanisms of these differences were analyzed with in vitro methods. At substoichiometric concentrations, the three drugs inhibit mi...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Recent insights into cell-mediated immunotherapy have led to a wave of new trials involving immunotherapy for prostate cancer. Vaccines have evolved from nonspecific immune stimulants like Bacillus Calmette-Guerin (BCG) to much more specific and potent strategies. Techniques currently being investigated include passiv...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-04-01 00:00:00
abstract::The human tumor cloning system is an in vitro assay that has been used to predict response of patients' tumors to conventional antineoplastic agents as well as to biologic agents. In addition, the assay has been used to screen for antitumor activity of newly discovered cytotoxics and biologics. The purpose of the pres...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Over the past three decades conceptual approaches to breast cancer have led to improvements in locoregional therapy and early diagnosis. Systematic screening programs with mammography reduce disease-specific mortality by 25% to 30%, while many patients with early breast cancer receive optimal breast-conserving treatme...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-08-01 00:00:00
abstract::Lung cancer represents the leading cause of cancer mortality worldwide. Its incidence has declined in men but is increasing in women, assuring that this largely preventable disease will continue to affect millions. In small cell lung cancer, the advent of chemotherapy in the 1970s and continued refinements in the 1980...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1997-08-01 00:00:00
abstract::The mainstay of screening for breast cancer is the mammogram. There are several randomized control trials that demonstrate a significant decrease in breast cancer mortality when compared to women without screening mammography included in their care. Digital mammography has improved detection in the dense breast. With ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2010.11.004
更新日期:2011-02-01 00:00:00
abstract::Preclinical studies with zoledronic acid (Zometa; Novartis Pharmaceuticals Corp, East Hanover, NJ) have shown its potential in malignant bone disease. Clinical studies in the treatment of hypercalcemia of malignancy have been completed, as have phase I and II trials in patients with cancer and pre-existing bone metast...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验,评审
doi:10.1016/s0093-7754(01)90260-x
更新日期:2001-04-01 00:00:00
abstract::Recent changes to the staging of melanoma, coupled with advances in surgical and medical treatment, have resulted in new methods for diagnostic evaluation and reporting of melanocytic lesions by pathologists. This review provides an update on recent changes in evaluation and reporting of primary melanoma, evaluation o...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2012.01.005
更新日期:2012-04-01 00:00:00