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 lesions, and produce synergistic cell kill. In vitro experiments using clinically achievable doses and schedules of these antimetabolites demonstrated cytotoxic synergy with the three-drug combination, but little or no such synergy with either antimetabolite plus cisplatin. The inclusion of hydroxyurea was necessary to achieve maximum synergy. Increased levels and persistence of cisplatin-induced DNA interstrand cross-links were observed, suggesting repair inhibition may have occurred. The dose of cisplatin required to inhibit colony formation by 90% was reduced approximately one third, even after normalization for the cytotoxic component(s) of hydroxyurea, cytarabine, and hydroxyurea plus cytarabine. Using one of the two optimal in vitro schedules for the three-drug combination, we performed a clinical pilot study in two patient cohorts (with and without prior systemic therapy). Administration of the program was feasible, and resulted in dose-limiting thrombocytopenia only in the cohort with prior chemotherapy. Azotemia was treatment-limiting in responding patients. Responses were observed in patients with a variety of solid tumors, including several patients who had previously failed cisplatin therapy. Modifications of this program are discussed, which have, to date, significantly decreased the toxicity concerns raised by the first trial. Phase II trials are planned in patients with a variety of cisplatin-responsive and nonresponsive neoplasms.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Albain KS,Swinnen LJ,Erickson LC,Stiff PJ,Fisher SG,Fisher RIsubject
Has Abstractpub_date
1992-06-01 00:00:00pages
102-9issue
3 Suppl 9eissn
0093-7754issn
1532-8708journal_volume
19pub_type
杂志文章abstract::Gemcitabine is a novel nucleoside analogue that has demonstrated activity against several solid tumors. A large phase II study has been performed in Europe and Canada with a total enrollment of 161 non-small cell lung cancer patients, 26 of whom were from the Institut Gustave-Roussy. Patient characteristics were the s...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1997-04-01 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin production in pathologic states such as inflammatory processes and cancer. The enzyme is often overexpressed in premalignant lesions and various cancers, including cancer of the lung. Inhibition of this enzyme with selective COX-2 inhibitors was found to ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2003.12.014
更新日期:2004-02-01 00:00:00
abstract::Almost 125 years after the first documented case, pulmonary metastasectomy is still poorly understood. No other organ is subject to the wide histologic variety of metastatic insults, and this fact has complicated a complete exposition of when pulmonary metastasectomy may be beneficial. Many physicians still consider p...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.03.004
更新日期:2007-06-01 00:00:00
abstract::The efficacy and toxicity of combination intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) were evaluated in 70 newly diagnosed patients with advanced-stage epithelial ovarian cancer. Cycles were administered at 4-week intervals for a total of six cycles, and treatment was provided on an outpatient ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1992-02-01 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::Thus far the development of adjuvant therapies in melanoma has suffered greatly from the lack of effective drugs in stage IV melanoma. Chemotherapy, cytokines, vaccines, and combinations of drugs have been used with minimal success. This has led to adjuvant therapies that are not used uniformly or widely because of th...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2010.09.009
更新日期:2010-10-01 00:00:00
abstract::Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecu...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2014.12.004
更新日期:2015-02-01 00:00:00
abstract::Non-Hodgkin's lymphoma (NHL) is not a single disease, but a group of closely related B- and T-cell cancers of the lymphatic system. The incidence of NHL is rising, particularly in the countries of the industrialized world. The increased incidence is poorly understood, but several risk factors have been postulated to b...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2005.01.008
更新日期:2005-02-01 00:00:00
abstract::Alterations in chromatin structure resulting from aberrant DNA methylation and perturbations of the histone code profoundly influence gene expression during pulmonary carcinogenesis. Recent studies indicate that DNA demethylating agents and histone deacetylase (HDAC) inhibitors synergistically induce gene expression a...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.07.007
更新日期:2005-10-01 00:00:00
abstract::Patients with advanced colorectal cancer were randomized to receive either fluorouracil (5-FU) 370 mg/m2 IV days 1 to 5 followed by weekly applications of 5-FU 600 mg/m2 or the same doses of 5-FU preceded by folinic acid 200 mg/m2. Because of toxicity, the weekly 5-FU dose in the combination treatment schedule was red...
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::From this brief review is should be evident that the hereditary varieties of common cancers are characterized by a high degree of genetic heterogeneity. The specific types of hereditary cancers can be identified by focusing on the histologic types and sites of involvement, not only of the primary neoplasm, but also of...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1978-03-01 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::Quality of life (QOL) is an important consideration in the treatment of patients with advanced lung cancer because treatment is largely palliative. Moreover, QOL predicts survival in non-small cell lung cancer, and there is increasing acceptance by clinicians and regulatory authorities of symptoms and QOL as primary o...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.10.004
更新日期:2004-12-01 00:00:00
abstract::First-line therapy for men with metastatic or recurrent prostate cancer following definitive local therapy is medical or surgical castration. Though effective initially in most patients, the majority of tumors develop castration resistance, necessitating the addition of further therapy. The historic treatment paradigm...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2013.04.015
更新日期:2013-06-01 00:00:00
abstract::Adrenocortical cancer (ACC) is a rare, challenging disease with a broad range of clinical presentations. Often presenting in an advanced stage with a large, locally invasive primary tumor or with Cushing's syndrome, it requires a multidisciplinary approach to treatment. We discuss controversies in the evaluation and m...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2010.10.011
更新日期:2010-12-01 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::ZD1839 (Iressa; AstraZeneca Pharmaceuticals LP, Wilmington, DE) is an orally active, selective inhibitor of epidermal growth factor receptor-tyrosine kinase (EGFR-TK) that blocks signaling pathways responsible for driving proliferation, invasion, and survival of cancer cells. In preclinical studies of cell lines and h...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2003.50028
更新日期:2003-02-01 00:00:00
abstract::Bendamustine has clinical potential in the treatment of low-grade non-Hodgkin's lymphoma (NHL). As a single agent, bendamustine has been used in two studies in patients with relapsed or refractory low-grade NHL. When bendamustine 120 mg/m(2) was given on days 1 and 2, the overall response rate was 73% with complete re...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.34877
更新日期:2002-08-01 00:00:00
abstract::A major consequence of administering increasingly aggressive therapies (chemotherapy with or without radiation therapy) in the treatment of non-small cell lung cancer is the adverse effects on the bone marrow that may lead to neutropenia, thrombocytopenia, and/or anemia. Myelosuppression or bone marrow toxicity may al...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.03.014
更新日期:2005-04-01 00:00:00
abstract::The purpose of this study was to evaluate the combination of gemcitabine, paclitaxel, and carboplatin in patients with advanced non-small cell lung cancer. Previously untreated patients with stage IIIB or IV non-small cell lung cancer were enrolled into this trial. Sixty-nine patients from the phase II portion and eig...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2000-02-01 00:00:00
abstract::Treatment of hormone-refractory prostate cancer (HRPC) historically has shown limited efficacy. However, taxane-based chemotherapy regimens recently have demonstrated more promising results. Several groups have reported significant efficacy and minimal toxicity in patients with hormone-refractory disease receiving est...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::At Indiana University, we began clinical trials with ifosfamide in 1981. Although our initial efforts were in a variety of tumor types, including pancreatic cancer, we have most recently focused our attention on two tumors that have historically exhibited a higher degree of chemosensitivity--testicular cancer and smal...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1992-02-01 00:00:00
abstract::Lung cancer is the leading cause of cancer death in the United States. Despite evidence of molecular abnormalities in biological specimens, progress in this disease is hampered by the lack of diagnostic markers useful for clinical practice. The majority of patients with lung cancer are still diagnosed at an advanced s...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.02.009
更新日期:2005-06-01 00:00:00
abstract::Many patients with Hodgkin's and non-Hodgkin's lymphoma (NHL) can be cured today with combination chemotherapy and/or radiotherapy. However, for patients with suboptimal responses to initial therapy or for patients with refractory or relapsed disease, salvage therapy alone is usually inadequate to achieve long-term su...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1998-08-01 00:00:00
abstract::Non-platinum combination regimens have been developed for advanced non--small cell lung cancer using the novel and active agents docetaxel, gemcitabine, vinorelbine, and irinotecan. The aim of these combinations is to equal or exceed the survival benefits achieved with cisplatin doublets while minimizing toxicity. Of ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:2001-06-01 00:00:00
abstract::The options available to patients with advanced non-small cell lung cancer (NSCLC) resistant or refractory to first-line chemotherapy are very limited. The older-generation drugs (etoposide, vindesine, epirubicin, and cisplatin) that are active against previously untreated NSCLC do not achieve a response rate greater ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1998-06-01 00:00:00
abstract::We resected 158 cases of hepatocellular carcinoma (HCC), including 20 (12.6%) cases of large HCC. These 20 cases were divided into group 1 (curative resection, n = 9) and group 2 (noncurative resection, n = 11). The clinicopathologic features and long-term survival of the cases were evaluated. In groups 1 and 2, porta...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::Successful allogeneic hematopoietic stem cell transplantation (HSCT) and solid organ transplantation require development of a degree of immune tolerance against allogeneic antigens. T lymphocytes play a critical role in allograft rejection, graft failure, and graft-versus-host disease (GVHD). T-cell tolerance occurs b...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2012.10.001
更新日期:2012-12-01 00:00:00
abstract::Locoregionally advanced unresectable non-small cell lung cancer is defined by bulky primary site disease and/or regionally advanced lymphadenopathy involving the contralateral mediastinum and/or supraclavicular lymph nodes. These tumors are not amenable to curative-intent surgical resection but can be approached with ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-10-01 00:00:00
abstract::In this feasibility study, a 3-hour infusion of 225 mg/m2 paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was combined with carboplatin dosed to an area under the concentration-time curve of 6 to treat patients with stage T2N0, T1-2N1, or T3N0-1 (excluding superior sulcus tumors) non-small cell lung ca...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00