Studies with ZD1839 in preclinical models.

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 human tumor xenografts, ZD1839 as single-agent therapy produced growth inhibition in a wide variety of common solid tumor types including lung, prostate, breast, colon, and ovarian cancers. In these models, ZD1839 inhibited growth of tumor xenografts with high, moderate, and low expression of EGFR. The A431 vulvar carcinoma model, which expresses abnormally high levels of EGFR, was particularly sensitive to ZD1839 treatment, leading to tumor regression. When ZD1839 was coadministered with cytotoxic chemotherapy agents or radiotherapy, additive or even synergistic antitumor activity was achieved. The inhibition observed with ZD1839 treatment was not restricted to advanced metastatic tumors, but also extended to early lesions such as breast xenografts of human ductal carcinoma in situ. Inhibition of EGFR-TK has also been shown to delay the onset of tumor development in a transgenic animal model. The diverse and profound antitumor activities attained with ZD1839 treatment in tumor cells and in xenograft tumor models provided the rationale for clinical development of ZD1839. Ongoing preclinical studies continue to support the importance of EGFR-TK activity in the biology of solid tumors.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Sirotnak FM

doi

10.1053/sonc.2003.50028

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

12-20

issue

1 Suppl 1

eissn

0093-7754

issn

1532-8708

pii

S0093-7754(02)00030-1

journal_volume

30

pub_type

杂志文章,评审
  • 3'-deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography for early prediction of response to chemoradiotherapy--a clinical application model of esophageal cancer.

    abstract::Early detection of response to neoadjuvant chemoradiation in esophageal cancer may allow individualization of treatment strategies and avoidance of unnecessary treatment. Although positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) permits detection of changes in tumor proliferation before any chan...

    journal_title:Seminars in oncology

    pub_type: 杂志文章

    doi:10.1053/j.seminoncol.2007.01.002

    authors: Chao KS

    更新日期:2007-04-01 00:00:00

  • Liver transplantation in Langerhans' cell histiocytosis (histiocytosis X).

    abstract::Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious oste...

    journal_title:Seminars in oncology

    pub_type: 杂志文章

    doi:

    authors: Concepcion W,Esquivel CO,Terry A,Nakazato P,Garcia-Kennedy R,Houssin D,Cox KL

    更新日期:1991-02-01 00:00:00

  • Clinicopathologic factors influencing the long-term prognosis following hepatic resection for large hepatocellular carcinoma more than 10 cm in diameter.

    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:

    authors: Noguchi T,Kawarada Y,Kitagawa M,Ito F,Sakurai H,Machishi H,Yamagiwa K,Yokoi H,Mizumoto R

    更新日期:1997-04-01 00:00:00

  • Carcinoembryonic antigen-based vaccines.

    abstract::Carcinoembryonic antigen (CEA) is a glycoprotein that is normally expressed in certain parts of the body and commonly overexpressed in most carcinomas of the colon, rectum, breast, lung, pancreas, and gastrointestinal tract. Increased expression of CEA promotes increased intercellular adhesions, which may lead to meta...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1016/s0093-7754(03)00233-1

    authors: Marshall J

    更新日期:2003-06-01 00:00:00

  • Epidemiology of acute myelogenous leukemia.

    abstract::The epidemiologic literature suggests that environmental exposures, familial susceptibility, and cytogenetic changes affect AML risk in childhood and adulthood. Unfortunately, many studies are limited by inadequate sample sizes, imprecise case definition, or inadequate exposure measurement. Few studies have singled ou...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Sandler DP

    更新日期:1987-12-01 00:00:00

  • Results of a compassionate-use program using intravenous ondansetron to prevent nausea and vomiting in patients receiving emetogenic cancer chemotherapy.

    abstract::This study reports the effectiveness and side effects of intravenous ondansetron as a single-agent antiemetic therapy for patients receiving emetogenic cancer chemotherapy under a compassionate-use program for patients not enrolled in controlled clinical trials. Patients were > or = 7 years old and had uncontrolled na...

    journal_title:Seminars in oncology

    pub_type: 杂志文章

    doi:

    authors: Berry WR,House KW,Lee JT,Plagge PB,Meshad MW,Grapski R

    更新日期:1992-12-01 00:00:00

  • Aromatase inhibitors and breast cancer.

    abstract::Selective aromatase inhibitors cause regression of breast carcinomas by reducing estrogen production via inhibition of the enzyme aromatase (estrogen synthetase). A higher incidence of hormone-dependent breast cancer occurs in postmenopausal women than in younger women. Thus, total estrogen blockade is more likely to ...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Brodie AM,Njar VC

    更新日期:1996-08-01 00:00:00

  • What is the optimal dose and duration of treatment with etoposide? I. Maximum tolerated duration of daily treatment with 50, 75, and 100 mg of oral etoposide.

    abstract::Because etoposide is a cell-cycle phase-specific drug, its degree of cytotoxicity likely relies on duration of cell exposure to a specific concentration. We investigated the maximum tolerated duration of oral etoposide treatment at doses of 100, 75, and 50 mg/d in previously treated patients with biopsy-proven, advanc...

    journal_title:Seminars in oncology

    pub_type: 杂志文章

    doi:

    authors: Splinter TA,van der Gaast A,Kok TC

    更新日期:1992-12-01 00:00:00

  • Unraveling biologic therapy for Bcl-2-expressing malignancies.

    abstract::Cancer cells that express excessive levels of Bcl-2 pose a major problem in the delivery of curative therapy. Most treatments for such cancer involve chemotherapy to induce the apoptotic process. While these therapies often result in disease control for periods of time, failure to initiate apoptosis as a result of acq...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1053/j.seminoncol.2004.10.014

    authors: Cotter FE

    更新日期:2004-12-01 00:00:00

  • The history of ifosfamide.

    abstract::Ifosfamide was developed by investigators at Asta-Werke in Germany. Its chemical structure differs from that of cyclophosphamide by the transposition of one of the side chain chloroethyl groups to the ring nitrogen. In several preclinical models, ifosfamide had greater activity than cyclophosphamide. It produced less ...

    journal_title:Seminars in oncology

    pub_type: 历史文章,杂志文章

    doi:

    authors: Loehrer PJ Sr

    更新日期:1992-12-01 00:00:00

  • Molecular biology of colorectal cancer: new targets.

    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

    authors: Kitisin K,Mishra L

    更新日期:2006-12-01 00:00:00

  • Intraperitoneal cisplatin chemotherapy in the management of ovarian carcinoma.

    abstract::Phase I trials of the intraperitoneal (IP) administration of cisplatin have demonstrated that the drug can be safely delivered by this route with a major increase in exposure (approximately tenfold to 15-fold) of the cavity to the cytotoxic agent compared with that of the systemic circulation. Phase I trials of IP cis...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Markman M

    更新日期:1989-08-01 00:00:00

  • Pox viral vaccine approaches.

    abstract::Recent advances in understanding tumor-specific immunity have introduced new excitement in the clinical development of vaccines for the treatment of cancer. A better understanding of basic immunologic principles has led to a variety of techniques for enhancing tumor-specific immunity through vaccination. Approaches to...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1053/j.seminoncol.2005.09.006

    authors: Arlen PM,Kaufman HL,DiPaola RS

    更新日期:2005-12-01 00:00:00

  • Overview of studies on endometrial cancer and other types of cancer in humans: perspectives of an epidemiologist.

    abstract::The epidemiologic studies relevant to the hypothesis that exposure to tamoxifen is associated with risk of cancer of the endometrium and perhaps other organs are described, summarized, and evaluated. One large body of data comes from the randomized trials of tamoxifen as a therapeutic agent against established breast ...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: MacMahon B

    更新日期:1997-02-01 00:00:00

  • Should radiotherapy be standard therapy for brain tumors in the elderly? Cons.

    abstract::Elderly patients with malignant gliomas present unique treatment challenges. Data are limited on the efficacy of various treatment modalities for high-grade gliomas in the elderly patient population, particularly for patients over 70 years of age, and the most appropriate treatment strategies remain a matter of debate...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1053/j.seminoncol.2003.11.027

    authors: Chinot OL

    更新日期:2003-12-01 00:00:00

  • Antifolates in clinical development.

    abstract::Many novel antifolate compounds with unique pharmacologic properties are currently in clinical development. These newer antifolates differ from methotrexate, the most widely used and studied drug in this class, in terms of their lipid solubility and cellular transport affinity, their level of polyglutamation, and thei...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Takimoto CH

    更新日期:1997-10-01 00:00:00

  • High-dose ifosfamide in the treatment of advanced soft tissue sarcomas.

    abstract::Ifosfamide, an oxazaphosphorine analogue, is now commonly used in first-line anthracycline-containing regimens for advanced soft tissue sarcomas, based on its demonstrated single-agent activity in previously treated patients. At the Institut Gustave-Roussy, we performed a phase II study of high-dose ifosfamide without...

    journal_title:Seminars in oncology

    pub_type: 临床试验,杂志文章

    doi:

    authors: Tursz T

    更新日期:1996-06-01 00:00:00

  • Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer: a phase I trial.

    abstract::Recently, a randomized study conducted by the Gynecologic Oncology Group (GOG 111) demonstrated that, given by a 24-hour infusion, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is superior to combination cisplatin/cyclophosphamide in previously untreated patients with...

    journal_title:Seminars in oncology

    pub_type: 临床试验,杂志文章

    doi:

    authors: Meerpohl HG,du Bois A,Luck HJ,Kühnle H,Möbus V,Kreienberg R,Bauknecht T,Köchli O,Bochtler H,Diergarten K

    更新日期:1997-02-01 00:00:00

  • Phase I dose-escalation trial of paclitaxel and ifosfamide in patients with advanced non-small cell lung cancer.

    abstract::This phase I dose-escalation study was undertaken to determine the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide that could be administered without growth factors to previously untreated patients with non-small cell lung cancer. Forty patients with advanced n...

    journal_title:Seminars in oncology

    pub_type: 临床试验,杂志文章

    doi:

    authors: Shepherd FA,Latreille J,Paul K,Eisenhauer E

    更新日期:1996-12-01 00:00:00

  • Whole cell vaccines--past progress and future strategies.

    abstract::Cancer vaccines have shown success in curing tumors in preclinical models. Accumulating evidence also supports their ability to induce immune responses in patients. In many cases, these responses correlate with improved clinical outcomes. However, cancer vaccines have not yet demonstrated their true potential in clini...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1053/j.seminoncol.2012.02.007

    authors: Keenan BP,Jaffee EM

    更新日期:2012-06-01 00:00:00

  • Secondary chemoprevention of upper aerodigestive tract tumors.

    abstract::Patients with successfully treated upper aerodigestive tract (UADT) tumors commonly develop second primary tumors (SPTs). These tumors occur more often than chance would predict, arise in both the upper or lower aerodigestive tracts, are frequently preceded by leukoplakia, and are a major cause of treatment-related fa...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1016/s0093-7754(01)90048-x

    authors: Anderson WF,Hawk E,Berg CD

    更新日期:2001-02-01 00:00:00

  • The potential role of amifostine in conjunction with cisplatin in the treatment of locally advanced carcinoma of the cervix.

    abstract::The treatment of locally advanced carcinoma of the cervix with radiation therapy as a single modality is inadequate, specifically for stage III and IVA disease. While chemotherapy as single-modality therapy is ineffective in advanced cervical cancer, there is some evidence of efficacy when used in combination with rad...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Wadler S,Goldberg G,Fields A,Anderson P,Beitler JJ,Sood B,Haynes H,Runowicz C

    更新日期:1996-08-01 00:00:00

  • Lymphoma and myeloma in older patients.

    abstract::Lymphoma and myeloma represent an increasingly important cause of morbidity and mortality in the older patient group. Studies to date, while limited, suggest that there may be differences in the underlying biology of the tumor cell of some lymphoid malignancies in younger versus older patients. Significant new data wi...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1053/j.seminoncol.2003.12.030

    authors: Westin EH,Longo DL

    更新日期:2004-04-01 00:00:00

  • Adjuvant and neoadjuvant therapy for early stage non-small cell lung cancer.

    abstract::Lung cancer is the number one cause of cancer-related death in both men and women in the United States. Non-small cell lung cancer accounts for approximately 85% of these cases. Despite complete resection, long-term survival for patients with operable disease remains poor. Studies exploring postoperative chemotherapy ...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1016/s0093-7754(01)90056-9

    authors: Pisters KM

    更新日期:2001-08-01 00:00:00

  • Third-line salvage chemotherapy in Hodgkin's disease.

    abstract::CEP (CCNU, etoposide, and prednimustine) was tested as third-line chemotherapy in 40 patients resistant to both MOPP and ABVD. The observed response rate (complete remission, 35%, and partial remission, 25%) is encouraging. Treatment was generally well tolerated and all acute side effects were reversible. ...

    journal_title:Seminars in oncology

    pub_type: 杂志文章

    doi:

    authors: Bonadonna G,Viviani S,Valagussa P,Bonfante V,Santoro A

    更新日期:1985-03-01 00:00:00

  • Treatment of colon cancer based on biochemical modulation of fluoropyrimidines by hydroxyurea.

    abstract::Preclinical studies have indicated that hydroxyurea leads to enhancement of 5-fluorouracil (5-FU) activity when given after 5-FU. This is presumably due to hydroxyurea's actions resulting in maintaining low levels of deoxyuridine monophosphate pools. The combination of hydroxyurea and 5-FU has been tested in several i...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Muggia FM,Moran RG

    更新日期:1992-06-01 00:00:00

  • Familial cancer and cancer families.

    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:

    authors: Anderson DE

    更新日期:1978-03-01 00:00:00

  • Efficacy of endoscopic variceal ligation for bleeding esophageal varices in patients with tumor thrombus of the portal vein trunk (Vp3) associated with hepatocellular carcinoma.

    abstract::We studied the efficacy of endoscopic variceal ligation (EVL) in 16 patients with tumor thrombus of the portal vein trunk (Vp3) associated with hepatocellular carcinoma. The average (+/-SD) number of O rings used was 9.0 +/- 5.0 for the esophageal varices (n = 7) and 16.4 +/- 4.5 for the esophagogastric varices (n = 9...

    journal_title:Seminars in oncology

    pub_type: 杂志文章

    doi:

    authors: Kokubu S,Matsumoto Y,Murakami M,Shibata H,Saigenji K

    更新日期:1997-04-01 00:00:00

  • Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma.

    abstract::Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) is a genetically engineered monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human, immunoglobulin GI kappa anti-CD20 antibody mediates complement-dependent cell lysis and antibody-depend...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:

    authors: Grillo-López AJ,White CA,Varns C,Shen D,Wei A,McClure A,Dallaire BK

    更新日期:1999-10-01 00:00:00

  • Adjuvant therapy for gastric cancer.

    abstract::The curative management of gastric adenocarcinoma depends on complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are 70% to 80%. There is continued debate over whether more extensive lymph node dissection (D2) impro...

    journal_title:Seminars in oncology

    pub_type: 杂志文章,评审

    doi:10.1016/s0093-7754(03)00298-7

    authors: Macdonald JS

    更新日期:2003-08-01 00:00:00