Abstract:
PURPOSE:Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabine in patients with advanced esophagogastric cancer (AEGC). METHODS:Patients with AEGC were randomized to gemcitabine 1250 mg/m2 (i.v. days 1, 8) and cisplatin 80 mg/m2 (i.v. day 1) q 3 weeks with or without folic acid (450 µg/day p.o.) and vitamin B12 (1000 µg i.m. q 9 weeks). The primary endpoint was response rate (RR). Secondary endpoints included overall survival (OS), time to progression (TTP), toxicity, and exploratory biomarker analyses. Cisplatin sensitivity and intracellular platinum levels were determined in adenocarcinoma cell lines cultured under high and low folate conditions in vitro. RESULTS:Adenocarcinoma cells cultured in medium with high folate levels were more sensitive to cisplatin and this was associated with increased intracellular platinum levels. In the randomized phase 2 clinical trial, which ran from October 2004 to September 2013, treatment was initiated in 78 of 82 randomized pts, 39 in each study arm. The RR was similar; 42.1% for supplemented patients vs. 32.4% for unsupplemented patients; p = 0.4. Median OS and TTP were 10.0 and 5.9 months for supplemented vs. 7.7 and 5.4 months for unsupplemented patients (OS, p = 0.9; TTP, p = 0.9). Plasma homocysteine was lower in the supplemented group [n = 20, 6.9 ± 1.6 (mean ± standard error of mean, SEM) µM; vs. 12.5 ± 4.0 µM; p < 0.001]. There was no significant difference in the Cmax of gemcitabine and cisplatin in the two treatment groups. CONCLUSION:Folic acid and vitamin B12 supplementation do not improve the RR, PFS, or OS of cisplatin and gemcitabine in patients with AEGC.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
van Zweeden AA,van Groeningen CJ,Honeywell RJ,Giovannetti E,Ruijter R,Smorenburg CH,Giaccone G,Verheul HMW,Peters GJ,van der Vliet HJdoi
10.1007/s00280-018-3588-6subject
Has Abstractpub_date
2018-07-01 00:00:00pages
39-48issue
1eissn
0344-5704issn
1432-0843pii
10.1007/s00280-018-3588-6journal_volume
82pub_type
杂志文章,随机对照试验abstract::A simple fluorescent microscopic method demonstrated that adriamycin was distributed in two cellular compartments of living rat colon cancer cells. Adriamycin accumulated slowly in cytoplasmic granules, probably lysosomes, where it persisted long after the drug was removed from the medium. On the other hand, adriamyci...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00401439
更新日期:1984-01-01 00:00:00
abstract::We have studied the effects of the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-platin) on three human ovarian carcinoma cell lines - one sensitive to the drug (CH1), one with acquired resistance (CH1cisR) and one with intrinsic resistance (SKOV-3). Previous work has shown that the 50% inhibitory concen...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050413
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:There is considerable current interest in the use of thalidomide as a single agent or in combination with drugs such as cyclophosphamide in the treatment of multiple myeloma and other cancers. Our previous work has shown that thalidomide potentiates the antitumour activity of both cyclophosphamide and 5,6-dimet...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0753-2
更新日期:2004-05-01 00:00:00
abstract::The toxicity of single doses of the anthracycline epirubicin was compared in the rat after either the intravenous (i.v.; 2-6 mg/kg) or intraperitoneal (i.p.; 4-8 mg/kg) administration of the drug. These doses produced comparable acute toxicity that was characterised by a dose-dependent, transient reduction in body wei...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257620
更新日期:1989-01-01 00:00:00
abstract::The development of nitrosoureas has switched from more lipophilic derivatives to congeners with higher water-solubility, since this property was presumably associated with a decrease in myelosuppression. We have compared the therapeutic efficacy of clinically well-known lipophilic nitrosoureas BCNU, CCNU, and MeCCNU w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254194
更新日期:1983-01-01 00:00:00
abstract:PURPOSE:Some clinical studies on etoposide (Eto) have shown marked schedule dependency of the effect (starting at about 1 mg/l) and toxicity (over about 10 mg/l) whereas other studies have not confirmed these results. What are the conclusions we can draw from these inconsistent results when developing new low-dose (LD)...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-001-0418-y
更新日期:2002-04-01 00:00:00
abstract::AspCNU and SarCNU are two amino acid amide congeners (L-asparaginamide and sarcosinamide congeners) of chloroethylnitrosoureas. The in vitro myelotoxicity of these agents compared with BCNU at 1-8 micrograms/ml was determined in bone marrow cells from normal volunteers in the CFU-C assay. AspCNU and SarCNU were signif...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434356
更新日期:1985-01-01 00:00:00
abstract::GR63178A is the second pentacyclic pyrroloquinone to enter clinical trials as an anticancer drug. We developed a reversed-phase, gradient-elution high-performance liquid chromatography (HPLC) method along with a Bond Elut C2 mini-column sample-preparation technique for the analysis of GR63178A, its 9-hydroxy-metabolit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00684952
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Docetaxel, capecitabine, and cisplatin are effective chemotherapeutic agents for breast cancer with significant synergistic cytotoxicity demonstrated by in vitro studies. The purpose of this study was to assess the efficacy of a combination of docetaxel, capecitabine, and cisplatin (TXP) in patients diagnosed w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-010-1401-2
更新日期:2011-06-01 00:00:00
abstract::Intravenous (i.v.) administration of sodium thiosulfate reduces the toxicity of cis-diamminedichloroplatinum (II) (CDDP). This effect, which allows the use of increased CDDP doses, has been exploited clinically in the intraperitoneal (i.p.) treatment of intraabdominal tumors. Recently, attempts have been made to treat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257358
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:This study evaluated mechanistic differences of pralatrexate, methotrexate, and pemetrexed. METHODS:Inhibition of dihydrofolate reductase (DHFR) was quantified using recombinant human DHFR. Cellular uptake and folylpolyglutamate synthetase (FPGS) activity were determined using radiolabeled pralatrexate, methot...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0954-4
更新日期:2009-10-01 00:00:00
abstract::In recent years significant progress in the understanding of the immune biology of melanoma has evolved from the identification of melanoma antigens (MAs) recognized by T cells. MAs consist of intracellular proteins that are expressed on the surface of cancer cells in association with human leukocyte antigen (HLA) cla...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/pl00014052
更新日期:2000-01-01 00:00:00
abstract::Prostaglandins (PGs) have been shown to inhibit tumour metastases in experimental animal systems. Nafazatrom is a pyrazolinone derivative that increases endogenous prostacyclin (PGI2) and has experimental anti-cancer activity. In the present study, nafazatrom was given to 47 women with advanced breast cancer; objectiv...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00685120
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Doxorubicin-based chemotherapy is limited by the development of dose-dependent left ventricular dysfunction and congestive heart failure caused by reactive oxygen species (ROS). Uncoupling proteins (UCP) can inhibit mitochondrial ROS production as well as decrease myocyte damage from exogenous ROS. Prior studie...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1441-7
更新日期:2011-06-01 00:00:00
abstract::In a phase II study we evaluated the effect and toxicity of a new alkylating agent, PTT-119, in 26 patients with non-Hodgkin's lymphomas (NHL) resistant to or relapsed after other chemotherapy. PTT was scheduled by escalating the dose from 2.0 to 3.3 mg/kg every 3 weeks. Among 21 evaluable patients with NHL, 12 (57%) ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00273532
更新日期:1989-01-01 00:00:00
abstract::We previously reported (UroOncology 1:165, 2001) cross-resistance and collateral-sensitivity to 2-chlorodeoxyadenosine (CldAdo) and fludarabine (FaraA), respectively, in a human renal cell carcinoma selected for resistance to 2'-deoxytubercidin (Caki-dTub). Insofar that these drugs generally demonstrate cross resistan...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0351-1
更新日期:2007-04-01 00:00:00
abstract:PURPOSE:We designed a phase I/II trial of intraperitoneal (IP) docetaxel plus S-1 to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate its efficacy and safety in gastric cancer patients with peritoneal carcinomatosis (PC). METHODS:Patients with PC confirmed by laparoscopy or laparoto...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2122-0
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1447-1
更新日期:2010-11-01 00:00:00
abstract:PURPOSE:Although irinotecan monotherapy is often used in third-line treatment after the failure of taxanes in Japanese clinical practice, its survival benefit is still unclear. The aim of this study is to investigate the efficacy and safety of irinotecan monotherapy as third-line treatment. METHODS:Clinical data from ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3138-z
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:Polyamines are absolutely essential for maintaining tumor cell proliferation. PG-11047, a polyamine analogue, is a nonfunctional competitor of the natural polyamine spermine that has demonstrated anticancer activity in cells and animal models of multiple cancer types. Preclinical investigations into the effects...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04201-1
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVES:To investigate the effects and potential mechanisms of gambogic acid (GA), a naturally occurring anticancer agent, on the expression and regulation of telomerase in human gastric carcinoma cells. METHODS:GA-induced inhibition of cell proliferation was evaluated by the commonly employed MTT assay on two huma...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0177-2
更新日期:2006-10-01 00:00:00
abstract::The technique of alkaline elution was employed to study the interactions of methylene dimethane sulphonate (MDMS) and formaldehyde (HCHO) with DNA from Yoshida lymphosarcoma cells treated with these agents. MDMS and HCHO produced a proteinase sensitive filter retention which indicated the presence of DNA-protein cross...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00296247
更新日期:1987-01-01 00:00:00
abstract::The interactions of cisplatin, 5-fluorouracil, doxorubicin, mitomycin, carmustine (BCNU), cyclophosphamide, methotrexate and thio-TEPA were assessed at three neurotransmitter receptor binding sites. Each drug was inactive at concentrations as high as 10(-4) M in displacing the specific binding of 3H-spiperone to dopam...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254564
更新日期:1987-01-01 00:00:00
abstract::The chemotherapeutic effects of all-trans-retinoic acid (atRA) are mediated by the retinoic acid receptor beta (RARbeta), but RARbeta expression is reduced in a number of head and neck carcinoma (HNSCC) cells which causes resistance to RA treatment in half the patients with HNSCC. The possible mechanism for the reduce...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0970-3
更新日期:2005-11-01 00:00:00
abstract:PURPOSE:SU5416 is a novel small organic molecule that non-competitively inhibits the phosphorylation of the VEGF tyrosine kinase receptor, Flk-1. This phase IB study was performed to determine the safety, pharmacokinetics, and preliminary efficacy of the combination of SU5416 and paclitaxel in recurrent or metastatic c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-004-0871-5
更新日期:2005-03-01 00:00:00
abstract::6-[Bis-(2-chloroethyl)-amino]-6-deoxy-D-glucose (C-6) is a new glucose-containing nitrogen mustard that has significant activity for murine P388 leukemia with relative sparing of bone marrow in mice. The in vitro myelotoxicity of C-6 compared with that of melphalan, a clinically active, myelosuppressive nitrogen musta...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00256165
更新日期:1986-01-01 00:00:00
abstract::The oral bioavailability of methotrexate is variable and may be dose-dependent. The absorption of 'interval' oral methotrexate, which is given between cycles of chemotherapy, is unknown. The bioavailability of oral methotrexate has been studied in eight patients, acting as their own controls, to assess the effect of s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257121
更新日期:1984-01-01 00:00:00
abstract::Nine children with poor-prognosis malignancies--seven with advanced neuroblastoma and two with metastatic Ewing's sarcoma--were given high doses of melphalan (HDM), 150 mg/m2 (3 patients) and 180 mg/m2 (6 patients), as a 'late intensification' agent combined with noncryopreserved autologous bone marrow transplants. Me...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00263898
更新日期:1985-01-01 00:00:00
abstract::RS-1541, an acyl-derivative of rhizoxin (Fig. 1), is a potent antitumor compound. This agent showed cytotoxicity in vitro on some cultured human tumor cells, although it was less potent than rhizoxin. Rhizoxin exhibited antitumor effects by inhibiting the polymerization of tubulin, whereas RS-1541 did not inhibit tubu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689446
更新日期:1995-01-01 00:00:00
abstract::The pharmacokinetics of flavone acetic acid (FAA) after a dose of 4.8 mg/m2 given i.v. over 1 h was investigated in 13 patients with different solid tumors. The mean volume of distribution and clearance were 52 +/- 4 l/m2 and 2.6 +/- 0.2 l/h x m2, respectively. A tumor or metastasis biopsy was obtained from six patien...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02940298
更新日期:1990-01-01 00:00:00