Abstract:
BACKGROUND:The US Food and Drug Administration approved pemetrexed in February 2004 for the treatment of malignant pleural mesothelioma (MPM) in combination with cisplatin in patients with unresectable disease or for whom curative surgery is not an option. Pemetrexed is the first agent approved for the treatment of MPM. In August 2004, pemetrexed was approved as a second-line, single-agent treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). OBJECTIVES:The goals of this article were to summarize the pharmacology, pharmacokinetics, efficacy, and safety of pemetrexed, and to review its current and potential roles in therapy for MPM, NSCLC, and other oncologic conditions. METHODS:Relevant English-language literature was identified through searches of PubMed (1966-December 2004), International Pharmaceutical Abstracts, and the Proceedings of the American Society of Clinical Oncology (January 1995-December 2004). Search terms included pemetrexed, Alimta, MTA, multitargeted antifolate, LY231514, mesothelioma, MPM, non-small cell lung cancer, NSCLC, breast cancer, and pancreatic cancer. In addition to published literature, abstracts and posters presented at national and international scientific meetings were reviewed. RESULTS:Myelosuppression was the predominant dose-limiting toxicity of pemetrexed reported in Phase I studies. Identification of the correlation between poor folate status and increased pemetrexed toxicity in a multivariate analysis led to the requirement of folic acid and vitamin B12 supplementation for patients in all pemetrexed studies, with a resulting noted decrease in pemetrexed toxicity. A single, multicenter, randomized Phase III trial compared the efficacy of pemetrexed in combination with cisplatin versus cisplatin alone in the treatment of MPM. Response rates were 41.3% in the pemetrexed/cisplatin combination and 16.7% with single-agent cisplatin (P < 0.001). The median survival time for the pemetrexed/cisplatin combination was significantly longer at 12.1 months versus 9.3 months for cisplatin alone (P = 0.02). One international, multicenter, randomized Phase III trial in patients with NSCLC compared single-agent pemetrexed versus docetaxel in patients previously treated with chemotherapy. Overall response rates (9.1% and 8.8%) and median survival (8.3 months and 7.9 months) did not differ between pemetrexed and docetaxel (P = 0.105 and P = 0.226, respectively). Hematologic adverse effects-grade 3/4 neutropenia (40.2% vs 5.3%; P < 0.001), febrile neutropenia (12.7% vs 1.9%; P < 0.001), and neutropenic infections (3.3% vs 0%; P = 0.004)-were significantly greater in the docetaxel-treated patients than in the pemetrexed-treated patients, as was alopecia (37.7% vs 6.4%; P < 0.001). Results of an international, multicenter Phase III trial of pemetrexed in combination with gemcitabine conducted in patients with pancreatic cancer indicate that the combination is no more efficacious than single-agent gemcitabine. Results in other disease states are still preliminary. CONCLUSIONS:Pemetrexed is a multitargeted antifolate that has demonstrated antitumor activity in various tumor types as a single agent and in combination with other chemotherapeutic agents. Efficacy for the treatment of MPM in combination with cisplatin has been demonstrated, and approval as a second-line agent in NSCLC was based on response rate as a surrogate end point for survival. The addition of folic acid and vitamin B12 supplementation markedly reduced.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Rollins KD,Lindley Cdoi
10.1016/j.clinthera.2005.09.010subject
Has Abstractpub_date
2005-09-01 00:00:00pages
1343-82issue
9eissn
0149-2918issn
1879-114Xpii
S0149-2918(05)00175-Xjournal_volume
27pub_type
杂志文章,评审abstract::The pharmacodynamic parameter that appears to correlate best with a successful therapeutic outcome with beta-lactam antibiotics is the length of time the serum antibiotic concentration remains above the minimum inhibitory concentration (MIC) for the infecting pathogen. By maximizing this parameter, continuous administ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)86736-3
更新日期:1999-11-01 00:00:00
abstract:BACKGROUND:Tapentadol hydrochloride is a centrally acting oral analgesic approved by the US Food and Drug Administration in November 2008 for the treatment of moderate to severe acute pain. It is available as immediate-release 50-, 75-, and 100-mg tablets. OBJECTIVE:The purpose of this article is to review animal stud...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2009.12.003
更新日期:2009-12-01 00:00:00
abstract::Two groups of patients with idiopathic Parkinson's disease underwent quantified electroencephalography (EEGq) using fast Fourier transfer to assess the effects of treatment with citicholine. Evidence of cortical cognitive impairment was seen in one group but not in the other. Certain parameters were established which ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::The Southern California region Kaiser Permanente Medical Care Program, which serves 2.2 million patients, and the University of Southern California School of Pharmacy have designed and implemented a patient consultation study to determine the cost-effectiveness of three different approaches to providing pharmacist con...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/0149-2918(95)80077-8
更新日期:1995-09-01 00:00:00
abstract:BACKGROUND:Technologies in which a remote trigger is used to release drug from an implanted or injected device could enable on-demand release profiles that enhance therapeutic effectiveness or reduce systemic toxicity. A number of new materials have been developed that exhibit sensitivity to light, ultrasound, or elect...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2012.09.012
更新日期:2012-11-01 00:00:00
abstract::A meeting of 14 transplant and pharmacokinetic specialists from Europe and North America was convened in November 2001 to evaluate scientific and clinical data regarding the use of different formulations of cyclosporin A (CsA). The following consensus was achieved. (1) CsA is a critical-dose drug with a narrow therape...
journal_title:Clinical therapeutics
pub_type: 共识发展会议,杂志文章,评审
doi:10.1016/s0149-2918(03)80161-3
更新日期:2003-06-01 00:00:00
abstract::This prospective, clinical economic study was done to determine the cost impact of oral compared with intravenous (i.v.) ganciclovir for the maintenance treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). Efficacy and safety data were extracted from ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(96)80036-1
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND:In the treatment of chronic obstructive pulmonary disease (COPD), tiotropium bromide has a longer duration of action than ipratropium bromide; however, tiotropium bromide is a more expensive alternative treatment. At issue is whether tiotropium reduces the risk for hospital readmissions for COPD compared wit...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.10.007
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND:In the past decade, health insurers have increased their reliance on cost control policies such as prior authorization and 3-tier formularies. Little is known about how these policies are being applied to psychotropic medications, many of which have low rates of patient adherence. OBJECTIVE:This study repor...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2007.02.011
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:The primary purpose of this article was to consider the candidate disruptors of the development of a healthy microbiome in patients with autism. The reported abnormalities in the microbiome of individuals with autism are discussed. METHODS:This selected review used data from published articles related to the a...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.04.001
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:The incidence of Alzheimer's disease (AD) has been steadily increasing worldwide. AD is a serious disease that has both societal and economic impacts. The greatest risk factor for AD is aging. Thus, because of the rapidly aging population in Japan, the development of new, effective drugs for AD is urgently need...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.02.024
更新日期:2015-08-01 00:00:00
abstract::Detrusor instability, or urinary incontinence, is common in elderly patients, particularly elderly women. The clinical symptoms of overactive, or unstable, urinary bladder include urge urinary incontinence, urgency, and frequency. Mixed urinary incontinence, which comprises urge urinary incontinence and stress inconti...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/S0149-2918(00)88316-2
更新日期:1999-04-01 00:00:00
abstract:PURPOSE:Selection and prompt initiation of the appropriate empiric antimicrobial therapy are critical to decrease morbidity and mortality and shorten the length of hospitalization among patients with hospital-associated intra-abdominal infections (HA-IAIs). Therapeutic choices for the treatment of patients with HA-IAI ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.04.035
更新日期:2016-06-01 00:00:00
abstract::A study was undertaken to determine the usefulness of ubidecarenone in pulmonary rehabilitation in exercise training programs in the management of chronic obstructive pulmonary disease (COPD). The subjects were 20 patients with COPD who had been participating in an exercise training program for at least four weeks. Th...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND:The Intermountain Cystic Fibrosis Pediatric Center utilizes ticarcillin-clavulanate 400 mg/kg/d divided every 6 hours, (maximum 24 g/d). This dosing strategy is higher than the Food and Drug Administration (FDA)-approved package labeling. We evaluated the microbiologic efficacy of this dosing regimen. OBJEC...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.09.010
更新日期:2011-11-01 00:00:00
abstract::Absorption of the antiarrhythmic agent mexiletine from conventional capsules (200 mg) and two sustained-release formulations (360 and 432 mg) was studied in four healthy volunteer subjects, and use of the 360-mg preparation was studied in nine patients who had been using conventional capsules. In the four volunteers, ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract::Nicardipine hydrochloride is the first intravenous dihydropyridine calcium antagonist to become available in the United States. Its chemical structure makes it unique among its drug class and confers clinically useful properties for the treatment of acute cardiovascular conditions, such as ischemia, hypertension, cong...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1988-01-01 00:00:00
abstract::Etodolac, aspirin, and placebo were evaluated for efficacy and safety in 18 patients with adult-onset, active rheumatoid arthritis. This was a 12-week, double-blind, parallel-group study divided into drug titration and maintenance periods and preceded by a washout period of up to two weeks. The mean daily maintenance ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:Patients newly diagnosed with type 2 diabetes mellitus generally initiate therapy with either metformin [Met] or a sulfonylurea [SU] drug, followed by the addition of a second agent (Met, an SU drug, or a thiazolidinedione [TZD] drug) if the diabetes is not well controlled. If necessary, the usual third line...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.10.018
更新日期:2011-12-01 00:00:00
abstract:PURPOSE:New therapies, including daratumumab plus lenalidomide plus dexamethasone (DRd) and daratumumab plus bortezomib plus dexamethasone (DVd), have recently been approved in the United States for patients with multiple myeloma (MM) who have received at least 1 prior line of therapy. However, few treatments have been...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2018.01.014
更新日期:2018-03-01 00:00:00
abstract:PURPOSE:The benefits and disadvantages of cervical extraction during hysterectomy are unclear in the literature. We intended to compare total (TH) with subtotal or supracervical (SH) hysterectomy regarding intraoperative and postoperative outcomes (quality of life, sexual function, pain and cyclical bleeding). METHODS...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2019.02.006
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Postoperative nausea and vomiting (PONV) are distressing and frequent adverse effects (AEs) in women undergoing laparoscopic gynecologic surgery. Midazolam has been reported to be effective for preventing PONV in adults undergoing middle ear surgery and children undergoing strabismus surgery or tonsillectomy...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验,收录出版
doi:10.1016/j.clinthera.2010.08.005
更新日期:2010-08-01 00:00:00
abstract::The effects of treatment with epalrestat, an aldose reductase inhibitor, on peripheral neuropathy were studied in 45 patients with non-insulin-dependent diabetes mellitus (NIDDM). Epalrestat 150 mg three times daily was given for 24 weeks. Subjective symptoms, such as spontaneous pain in the lower extremities and numb...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/0149-2918(95)80111-1
更新日期:1995-05-01 00:00:00
abstract::In a double-blind study, 59 patients with chronic erosive gastritis received 50 mg of pirenzepine twice daily and 55 patients received 400 mg of cimetidine twice daily for six weeks. In both groups, days of pain, of heartburn, and of nausea per week were significantly reduced during treatment (P less than 0.01). After...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1989-11-01 00:00:00
abstract::Moxifloxacin (BAY 12-8039) is an investigational 8-methoxy-fluoroquinolone with broad-spectrum gram-positive and gram-negative activity. To determine the absolute bioavailability of moxifloxacin, this open-label, randomized, crossover study compared the pharmacokinetic characteristics of a single 100-mg dose administe...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S0149-2918(00)88306-X
更新日期:1999-03-01 00:00:00
abstract::Fourteen patients with serious infections caused by Staphylococcus aureus and other gram-positive bacteria were prospectively treated with chromatographically purified vancomycin in an open-label, nonrandomized study, between December 1986 and June 1987. Five patients were excluded from the evaluation of efficacy. Amo...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND:Amlodipine is a third-generation dihydropyridine calcium antagonist for the treatment of angina and hypertension. The relative bioavailability of a newly developed dispersible tablet as compared with an established branded formulation has not been reported in a Chinese population. OBJECTIVE:The aim of this ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2009.04.013
更新日期:2009-04-01 00:00:00
abstract::Since the introduction of angiotensin converting enzyme (ACE) inhibitors into clinical use, much information has been accumulated in animal models and man regarding their effects on renal function in different disease states. Enalapril, the first nonsulfhydryl ACE inhibitor approved for general use in the United State...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1989-09-01 00:00:00
abstract::Hemodynamic and electrophysiologic effects of procainamide, the pharmacokinetic properties of conventional and sustained-release forms of the drug, guidelines for its administration and dosage, and contraindications for and adverse effects of its use are outlined. A review of clinical studies of procainamide therapy c...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
abstract::The added hypotensive effect of bevantolol, a new cardioselective beta-blocker, was studied in 244 patients with mild to moderate essential hypertension following prior treatment with hydrochlorothiazide or placebo. After four weeks of monotherapy with 50 mg/day or 100 mg/day of hydrochlorothiazide or placebo, the mea...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1985-01-01 00:00:00