Abstract:
:Thirty patients with cisplatin-refractory germ cell tumor were treated with high-dose carboplatin, etoposide, and cyclophosphamide and autologous bone marrow transplantation. The total dose of carboplatin was 1500 mg/m2, etoposide 1200 mg/m2, and cyclophosphamide was increased by increments from 60 to 150 mg/kg. Twenty-five cycles of treatment, given to 17 patients, did not include granulocyte-colony stimulating factor (G-CSF). Nineteen cycles of high-dose chemotherapy, given to 13 patients at the 2 highest dose levels of cyclophosphamide, included G-CSF. The dose of cyclophosphamide was escalated to 150 mg/kg/cycle without prohibitive toxicity. The use of G-CSF resulted in a shorter duration of neutropenia (P = 0.07); the median number of days until the recovery of an absolute granulocyte count > 0.5 was 25 without G-CSF and 14 with G-CSF. The most frequent nonhematological toxicity was hepatic, and there were 2 (7%) treatment-related deaths. Thirteen (43%) patients achieved a complete response, and 8 are alive and free of disease (27%); 7 are in continuous complete response (23%), and 1 after resection of a solitary site of disease following a relapse after high-dose chemotherapy. Five patients had pharmacology studies performed to determine the area under the curve (AUC) of free and total platinum, carboplatin, etoposide, cyclophosphamide, and phosphoramide mustard. There was a decrease in the AUC of cyclophosphamide and an increase in the AUC of phosphoramide mustard, the "active" metabolite, with successive days of treatment. The interpatient variability of the AUC of cyclophosphamide/phosphoramide mustard that was demonstrated was most likely a result of each individual's metabolic capacity. The measured AUC of carboplatin and/or free platinum closely approximated the predicted AUC of carboplatin calculated by renal function in 3 of the 5 patients. In summary, cyclophosphamide administered at a dose of 50 mg/kg x 3 days was achieved with acceptable toxicity, and no further dose escalation is planned. High-dose carboplatin, etoposide, and cyclophosphamide achieved a 23% continuous complete response proportion (27% alive, free of disease) when used as third-line therapy in germ cell tumor patients refractory to cisplatin + ifosfamide-based chemotherapy. Ongoing studies are addressing the role of high-dose carboplatin-containing chemotherapy in previously untreated patients with poor prognostic features or as a part of first-line salvage.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Motzer RJ,Gulati SC,Tong WP,Menendez-Botet C,Lyn P,Mazumdar M,Vlamis V,Lin S,Bosl GJsubject
Has Abstractpub_date
1993-08-15 00:00:00pages
3730-5issue
16eissn
0008-5472issn
1538-7445journal_volume
53pub_type
临床试验,杂志文章相关文献
CANCER RESEARCH文献大全abstract::The macrophage content of spontaneous metastases has been quantified morphometrically for a panel of rodent tumors at different stages of metastatic tumor growth. Using a histochemical technique to selectively stain macrophages, we have evaluated the relative content of macrophages in spontaneous pulmonary metastases ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::Sporadic prostate carcinoma is the most common male cancer in the Western world, yet many of the major genetic events involved in the progression of this often fatal cancer remain to be elucidated. Numerous cytogenetic and allelotype studies have reported frequent loss of heterozygosity on chromosomal arm 10q in spora...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-11-15 00:00:00
abstract::Short-term exposure to diethyl ether strongly inhibits the metabolism of N-nitrosodimethylamine (NDMA). Twenty-six 6-week-old male Fischer 344 rats were exposed to ether vapor until their righting reflex was lost (approximately 2 min). The animals were removed from the ether and NDMA was immediately administered by i....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::Ataxia telangiectasia (AT) is an autosomal recessive disorder in which increased level of chromosome breakage and specific sensitivity to radiation and carcinogens have been reported. The effect of the radiomimetic drug bleomycin on chromosome breakage has been tested in skin fibroblasts of three patients with AT, two...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::We are in an era where the potential exists for deriving comprehensive profiles of DNA alterations characterizing each form of human cancer. Such profiles would provide invaluable insight into mechanisms underlying the evolution of each tumor type and will provide molecular markers, which could radically improve cance...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-04-15 00:00:00
abstract::Chicken chondrocytes isolated from 11-day-old chicken vertebrate cartilage were transformed by Rous sarcoma virus ts LA24 of the Prague strain as well as by the wild-type Prague strain of Rous sarcoma virus. The morphology of chondrocytes transformed by Rous sarcoma virus ts LA 24 was dependent on the temperature, and...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::Analysis of muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat by measurement of N-[methyl-3H]scopolamine binding has revealed a single homogenous population of muscarinic receptors in the tumor. The plasmalemma density (approximately 25 receptors/micron 2 of cell membrane surface) and dissociation...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::The immune system is a robust and often untapped accomplice of many standard cancer therapies. A majority of tumors exist in a state of immune tolerance where the patient's immune system has become insensitive to the cancer cells. Because of its lymphodepleting effects, chemotherapy has the potential to break this tol...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-3712
更新日期:2019-10-15 00:00:00
abstract::Androgen receptors (ARs) belong to the family of hormone receptors that are ligand-dependent transcription factors. Endocrine therapy provides effective treatment for prostate cancer until mutations arise that alter the ligand responsiveness of AR. In this study, structural models were developed for the functional dom...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::Preclinical and clinical development of agents that inhibit cell-cycle progression have brought an understanding of the feasibility of targeting various cell-cycle regulators in patients with cancer. Small molecule inhibitors targeting key proteins that participate in cell-cycle progression including the cyclin-depend...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-17-2782
更新日期:2018-01-15 00:00:00
abstract::ErbB2 and ErbB3, two members of the ErbB family, form a high-affinity heregulin coreceptor that elicits potent mitogenic and transforming signals, and clinical studies indicate that these receptors play an important role in tumor incidence and progression. To determine whether N-glycosylation is involved in the functi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3023
更新日期:2007-03-01 00:00:00
abstract::A monoblastic cell line U-937 (clone 4), was induced to differentiate along the monocytoid lineage by 12-O-tetradecanoylphorbol-13-acetate (TPA), retinoic acid (RA), and vitamin D3 (VD3). By immunochemical and morphological criteria the cells were found to differentiate into macrophage-like cells in the presence of al...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract::Recently, we have shown that the p53 tumor suppressor gene product can inhibit expression of the bcl-2 gene. In this report, we explored the molecular basis for p53-mediated down-regulation of bcl-2 gene expression using a cotransfection approach involving p53 expression plasmids and chloramphenicol acetyltransferase ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-06-15 00:00:00
abstract::Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-1617
更新日期:2016-02-15 00:00:00
abstract::The transcription factor activating transcription factor 2 (ATF2) has been shown to be associated with melanocytic oncogenesis and melanoma tumor proliferation in preclinical models. The clinical significance of ATF2 expression is unknown. To determine the prognostic value of ATF2 in melanoma, we evaluated the pattern...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract::Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy. The mechanisms of this intrinsic resistance are unknown. This study was designed to investigate the role of DNA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::K-ras gene mutations have been reported as early events in colorectal tumorigenesis, but their role in tumor initiation and development is still unclear. To analyze and compare K-ras mutational patterns between colorectal tissues at different stages of tumor progression in individual patients, 65 colorectal tissue sam...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-06-15 00:00:00
abstract::Data are presented in support of the hypothesis that malignant tumors, containing abnormally permeable, degenerating cells, can be selectively detected using monoclonal antibodies to intracellular antigens. Biodistribution, imaging, and autoradiographic studies were performed in nude mice transplanted with four differ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-10-15 00:00:00
abstract::Mutagenesis of protooncogenes has been postulated to contribute to the initiation and progression of human cancer. Activating mutations in the H-ras gene are predominantly single-base substitutions and are most frequently identified at codons 12, 13, and 61. We have analyzed the effects of DNA sequence context at spec...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-15 00:00:00
abstract::The effect of dietary intake of different levels of Menhaden fish oil on azoxymethane-induced carcinogenesis was examined in male F344 rats fed the semipurified diets. Starting at 5 weeks of age, groups of animals were fed the 5% corn oil (low corn oil) diet. At 7 weeks of age, all animals except the vehicle-treated c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::Curcumin, a plant polyphenol, is a widely studied chemopreventive agent with demonstrated antitumor activities in preclinical studies and low toxicity profiles in multiple clinical trials against human malignancies. We previously showed that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3025
更新日期:2010-03-01 00:00:00
abstract::Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignan...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6682
更新日期:2008-08-15 00:00:00
abstract::In this study, we show that rodent albumin is expressed by and cell surface localized on at least some murine tumor cells. We have been able to purify this tumor-expressed albumin from in vivo grown tumor masses. The tumor-expressed albumin, unlike normal serum albumin purified from blood, is capable of inhibiting T-c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1871
更新日期:2004-11-01 00:00:00
abstract::Quantitative optical cytochemistry permits the determination of many different parameters in whole cells or parts of cells. Total amounts of DNA, RNA, and protein and/or the amounts of these substances in nucleus or nucleolus are examples. Techniques in this field have contributed considerably to the development of ou...
journal_title:Cancer research
pub_type: 历史文章,杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::Cyclin D1/cyclin-dependent kinase 2 (Cdk2) complexes are present at high frequency in human breast cancer cell lines, but the significance of this observation is unknown. This report shows that expression of a cyclin D1-Cdk2 fusion protein under the control of the mouse mammary tumor virus (MMTV) promoter results in m...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3815
更新日期:2007-04-01 00:00:00
abstract::We showed that the PEA3 transcriptional factor interacted with LKB1, a serine/threonine kinase, which is somatically mutated in lung cancer. This interaction occurred through the ETS domain of PEA3 and the kinase domain of LKB1. Mutation of LKB1 in lung cancer cells stabilized PEA3. Reintroduction of wild-type (WT) LK...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2902
更新日期:2006-08-15 00:00:00
abstract::Hexose uptake during the progression of neoplasia in rat tracheal epithelial cells was studied by measuring the uptake of 2-deoxy[3H]glucose (2-dGlc) in nontumorigenic (C-18) and tumorigenic (T-8, 1000-WT) rat tracheal epithelial cell lines with varying degrees of cell association as well as in: normal primary cell cu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::Inhibition of angiogenesis has emerged as a key focus for the treatment of cancer, necessitating a better understanding of the downstream molecular targets of angiogenesis inhibitors. Endostatin, thrombospondin-1, fumagillin, and its synthetic derivative, TNP-470, are potent inhibitors of endothelial cell proliferatio...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like APOBEC3A and APOBEC3B have emerged as key mutation drivers in cancer. Here, we show that APOBEC3A and APOBEC3B activities impose a unique type of replication stress by inducing abasic sites at replication forks. In contrast to cells under other types ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-3389
更新日期:2017-09-01 00:00:00
abstract::17beta-Hydroxysteroid dehydrogenase type 12 (17beta-HSD12) has been shown to be involved in elongation of very long chain fatty acid (VLCFA) as well as in biosynthesis of estradiol (E2). 17beta-HSD12 expression was also reported in breast carcinomas but its functions have remained unknown. In this study, we examined t...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0821
更新日期:2009-02-15 00:00:00