Abstract:
:Preclinical models in vitro and in vivo have shown that tumor hypoxia alters the malignant cell phenotype, selecting for p53 mutations, stimulating angiogenesis and metastasis, and markedly reducing the efficacy of both radiotherapy and chemotherapy. Similarly, clinical studies measuring pretreatment tumor oxygen status confirm that the presence of hypoxia confers a negative impact on local control, disease-free survival, and overall survival. Despite these data and extensive past research efforts, the promise of developing selective hypoxic-cell sensitizers has been largely unfulfilled. In contrast, tirapazamine is the rationally designed prototype for a new class of therapeutic agents targeting tumor hypoxia: hypoxic cytotoxins. Tirapazamine is bioreductively activated in hypoxic cells and has been shown to potentiate the cytotoxicity of radiation and a number of chemotherapeutic drug classes, in particular platinum compounds and taxanes. This article reviews the preclinical and clinical development of tirapazamine, as well as current trials in non-small cell lung cancer designed to provide proof of principle for this new category of cancer therapeutics.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Gandara DR,Lara PN Jr,Goldberg Z,Le QT,Mack PC,Lau DH,Gumerlock PHdoi
10.1053/sonc.2002.31531subject
Has Abstractpub_date
2002-02-01 00:00:00pages
102-9issue
1 Suppl 4eissn
0093-7754issn
1532-8708pii
S0093-7754(02)50117-2journal_volume
29pub_type
杂志文章,评审abstract::A primary goal of current clinical cancer research is the identification of prognostic tumor subtypes. It is increasingly clear that tumor growth depends on both internal tumor factors, and factors that are external to the tumor, such as microenvironment. We recently showed that parameter values alone are less importa...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2015.05.004
更新日期:2015-08-01 00:00:00
abstract::Gemcitabine is an active agent in non-small cell lung cancer, with single-agent treatment producing response rates of approximately 20% and median survivals of approximately 7 to 9 months. In a pilot trial in advanced non-small cell lung cancer, the gemcitabine/carboplatin combination produced a response rate of 43% a...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1053/sonc.2002.34276
更新日期:2002-06-01 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::Advances in technology have accelerated the translation of genetics and genomics into the arena of cancer prevention. This provides unique opportunities to individualize cancer risk prediction so early intervention can either modify risk or allow for early diagnosis thereby potentially decreasing the morbidity and mor...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2010.05.005
更新日期:2010-08-01 00:00:00
abstract::Cisplatin/etoposide/bleomycin (DEB) was given as an outpatient regimen in a novel weekly schedule to 27 patients with recurrent and/or widely metastatic cancer of the head and neck region. Six of these patients also received mitomycin (DEB/M) when their disease failed to respond after at least three weekly DEB doses. ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1992-04-01 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::Many small cell carcinomas share morphological and physiological characteristics with normal and neoplastic cells of Pearse's APUD series, including pulmonary APUD cells and pulmonary carcinoid tumors. There is very likely more than one type of APUD cell in the lung, and conclusions that small cell carcinomas and carc...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1978-09-01 00:00:00
abstract::In order to correlate changes in morphology to changes in molecular attributes, we constructed a tissue microarray of thin and thick melanomas selected to represent progression from dysplasia to early and advanced melanoma. Hematoxylin and eosin (H&E) staining and immunohistology with antibodies to cyclin D1, p16, Ki6...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.09.014
更新日期:2007-12-01 00:00:00
abstract::It has been a challenge to find effective chemotherapeutic treatments for malignant mesothelioma. Over the last several decades numerous single-drug and combination regimens have been examined, but no standard treatment with chemotherapy alone has emerged. Possible explanations for this lack of success are the heterog...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.30231
更新日期:2002-02-01 00:00:00
abstract::Acute lymphoblastic leukemia (ALL) 5-year survival rates are approaching 90% in children and 50% in adults who are receiving contemporary risk-directed treatment protocols. Current efforts focus not only on further improving cure rate but also on patient quality of life. Hence, all protocols decrease or limit the use ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2009.05.002
更新日期:2009-08-01 00:00:00
abstract::Non-Hodgkin's lymphoma (NHL) is composed of a group of lymphoid malignancies that has been increasing in incidence at an annual rate of 4% to 7% over the last 20 years in both the United States and Europe. The reasons for this rise in incidence in NHL are not yet defined but most likely involve environmental exposures...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/sonc.2002.30152
更新日期:2002-02-01 00:00:00
abstract::The current oncology practice of treating cancer with aggressive doses of radiation and chemotherapy is potentially disastrous, as response and side effects vary depending on several factors including pharmacogenetics. This study is the first to evaluate esophageal cancer treatment with a pharmacogenetic paradigm and ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2005.04.031
更新日期:2005-12-01 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::Two phase II trials of mitoxantrone in refractory malignant lymphoma have been conducted. In the first of these, mitoxantrone (5 mg/m2) was given weekly for 6 weeks, and in the second, 14 mg/m2 was administered every 3 weeks. The first trial was conducted by the Southeastern Cancer Study Group (SECSG), and the second ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::For four decades, 5-fluorouracil was the only option available for patients with metastatic colorectal cancer. It provided a response rate of 15% to 20%, with a median survival of approximately 1 year. In the past 5 years, remarkable progress has been made in colorectal cancer research with the approval of irinotecan ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.04.022
更新日期:2005-12-01 00:00:00
abstract::One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activates multiple signaling cascades that promote carcinogenesis and immune evasion. Therefore, these molecules have been extensively targeted in cancer immunotherapy. Beyond EGFR signaling cascade inhibition, some of these agen...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2018.04.008
更新日期:2018-01-01 00:00:00
abstract::The human gammaherpesvirus family includes Epstein-Barr virus (EBV) and human herpesvirus (HHV)-8, also known as Kaposi sarcoma-associated herpesvirus (KSHV). In human immunodeficiency virus (HIV)-infected patients, both EBV and KSHV have been implicated in the development of a wide range of tumors. KSHV-associated di...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2014.12.026
更新日期:2015-04-01 00:00:00
abstract::It is a truism that a better understanding of the biology of breast cancer should lead to improvements in diagnosis and therapy. Despite this, our significantly improved grasp of breast cancer biology has had little direct therapeutic impact to date. The technologies used to treat breast cancer (surgery, radiation the...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-02-01 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::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::Hypercalcemia of malignancy (HCM) is a potentially life-threatening complication of cancer resulting from increased bone resorption by osteoclasts. Clinical management of HCM primarily consists of intravenous rehydration therapy combined with pharmaceutical agents that decrease osteoclast activity. Several generations...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.37417
更新日期:2002-12-01 00:00:00
abstract::Transitional cell carcinoma of the urothelium is a highly chemosensitive tumor. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. As shown in a recent phase III trial, the new gold standard should be considered gemcitabine/cisplatin, although toxici...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2001.22537
更新日期:2001-06-01 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::To evaluate the activity of thalidomide in Waldenstrom's macroglobulinemia (WM), 20 patients were treated on a dose schedule that escalated from 200 mg/d to 600 mg/d. On an intention-to-treat basis, five (25%) patients achieved a partial response, which was noted within 3 months of treatment. Adverse effects were comm...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2003.50079
更新日期:2003-04-01 00:00:00
abstract::Cyclooxygenase (COX) enzyme-dependent arachidonic acid metabolites occupy key positions in important physiologic processes such as immunity, reproduction, and vascular integrity. Large retrospective and prospective population-based studies have shown that the use of both nonselective, nonsteroidal anti-inflammatory dr...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(03)00120-9
更新日期:2003-06-01 00:00:00
abstract::The outcome of chemotherapy for patients with stage IV melanoma is unsatisfactory, since durable responses are rarely achieved. More experimental treatments, such as vaccine approaches, antibody treatments, and gene therapy are being developed and are of high scientific interest; however, their efficacy in advanced me...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.35240
更新日期:2002-10-01 00:00:00
abstract::Platelet-derived microparticles (PMPs) represent the most abundant microparticle (MP) subtype. Their presence reflects platelet activity, physiopathology, and the thrombotic state of cancer patients. The quantity and composition of PMPs strictly depends on the way MPs were generated. Because platelets play a key role ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2014.04.010
更新日期:2014-06-01 00:00:00
abstract::The use of adjuvant radiation therapy and chemotherapy diminishes the likelihood of local-regional and distant recurrences and appears to prolong survival in patients who have undergone a complete surgical resection of a Dukes-Kirklin stage B2 or C rectal cancer. Patients with this malignant condition rarely develop p...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::Diffuse large B-cell lymphoma (DLCL) is the most frequently diagnosed subtype of non-Hodgkin's lymphoma (NHL), and more than 50% of cases present in patients over 60 years of age. Although cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) is currently regarded as the gold standard treatment for DLCL, less tha...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.32749
更新日期:2002-04-01 00:00:00
abstract::Present status of gastric cancer surgery in Japan and several new procedures are reviewed in this article. Japanese treatment results of this disease were significantly better than Western results even when stages were adjusted. Generally speaking, Japanese surgical procedures are more aggressive and meticulous compar...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-06-01 00:00:00