Online citations, reference lists, and bibliographies.
← Back to Search

FDA Drug Approval Summaries: Pemetrexed (Alimta).

M. Hazarika, R. M. White, J. Johnson, R. Pazdur
Published 2004 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.
This paper references
10.1016/0360-3016(91)90054-8
Deterioration in lung function following hemithorax irradiation for pleural mesothelioma.
P. Maasilta (1991)
10.1378/CHEST.108.4.1122
A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group.
V. Rusch (1995)
10.1056/NEJM198206173062403
The pathogenesis of asbestos-associated diseases.
J. Craighead (1982)
10.1097/00000658-199609000-00005
Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients.
D. Sugarbaker (1996)
10.1200/JCO.1999.17.1.25
Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study.
M. Byrne (1999)
10.1016/S0959-8049(00)00072-1
A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma.
P. Rougier (2000)
LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes.
C. Shih (1997)
10.1200/JCO.1993.11.8.1559
Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B.
A. Chahinian (1993)
10.1016/S0022-5223(98)70274-0
Preoperative tumor volume is associated with outcome in malignant pleural mesothelioma.
H. Pass (1998)
10.1016/S0169-5002(00)00166-5
Gemcitabine for malignant mesothelioma: A phase II trial by the Cancer and Leukemia Group B.
H. Kindler (2001)
Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy.
C. Niyikiza (2002)
10.1002/(SICI)1097-4652(199908)180:2<167::AID-JCP4>3.0.CO;2-Q
New molecular and epidemiological issues in mesothelioma: Role of SV40
M. Carbone (1999)
10.1093/OXFORDJOURNALS.ANNONC.A058846
Weekly high-dose cisplatin in malignant pleural mesothelioma.
A. Planting (1994)
10.1200/JCO.2003.11.136
Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
N. Vogelzang (2003)
10.1043/0003-9985(1999)123<0039:PFTEOS>2.0.CO;2
Protocol for the examination of specimens from patients with malignant pleural mesothelioma: a basis for checklists. Cancer Committee, College of American Pathologists.
G. Nash (1999)
10.1016/S0022-5223(96)70342-2
The importance of surgical staging in the treatment of malignant pleural mesothelioma.
V. Rusch (1996)
10.1038/bjc.1992.200
High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study.
O. Solheim (1992)



This paper is referenced by
10.1371/journal.pone.0186137
Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models
M. Alfaleh (2017)
10.1097/JTO.0b013e31817c73ec
Single-Agent Pemetrexed for Chemonaïve and Pretreated Patients with Malignant Pleural Mesothelioma: Results of an International Expanded Access Program
Paul Taylor (2008)
10.1038/s41397-018-0047-z
Genetic markers in methotrexate treatments
Andrea Giletti (2018)
10.1007/S11912-005-0048-3
New therapeutic options for mesothelioma
Ranjit K. Goudar (2005)
10.1002/jso.24960
Comparison of open and closed abdomen techniques for the delivery of intraperitoneal pemetrexed using a murine model
D. Badrudin (2018)
Malignant Pleural Mesothelioma and the Role of Non – Operative Therapies Kelvin
C. Ng (2018)
10.3892/ol.2018.7890
Antitumor activity of kinetochore-associated protein 2 siRNA against lung cancer patient-derived tumor xenografts.
Yukimasa Makita (2018)
10.1016/J.LUNGCAN.2006.06.017
Promoter methylation of RASSF1A, RARbeta and DAPK predict poor prognosis of patients with malignant mesothelioma.
J. Fischer (2006)
10.3816/CLC.2010.n.005
Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study.
N. Katirtzoglou (2010)
10.3109/9781841848679.006
First-line therapy of advanced non-small cell lung cancer not harboring an activating EGFR mutation
Cesare Gridelli (2012)
10.1016/j.ijbiomac.2017.05.015
Lipid drug conjugate nanoparticle as a potential nanocarrier for the oral delivery of pemetrexed diacid: Formulation design, characterization, ex vivo, and in vivo assessment.
Kriti Soni (2017)
Contribution of activin signals to progression of malignant pleural mesothelioma and evaluation of therapeutic implications
J. Münzker (2011)
Pyrrolo[2,3-d]pyrimidine Classical Antifolates for Targeted Cancer Chemotherapy- Applications of Bioisosteric and Regioisomeric Substitutions for Improved Tumor-Selectivity and Potency
M. Ravindra (2018)
10.1016/j.drup.2012.07.002
Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance.
Nitzan Gonen (2012)
10.1016/J.CLINTHERA.2005.09.010
Pemetrexed: a multitargeted antifolate.
K. D. Rollins (2005)
10.1016/J.BLRE.2006.05.001
Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment.
L. Solomon (2007)
10.1097/JTO.0b013e31817c73d6
Pemetrexed Plus Cisplatin or Pemetrexed Plus Carboplatin for Chemonaïve Patients with Malignant Pleural Mesothelioma: Results of the International Expanded Access Program
A. Santoro (2008)
10.4155/TDE.12.42
Distribution of effervescent inhalable nanoparticles after pulmonary delivery: an in vivo study.
M. AlHallak (2012)
10.2217/LMT.14.16
Pemetrexed in non-small-cell lung cancer
M. Dediu (2014)
10.1021/acsnano.6b07196
One-Component Supramolecular Filament Hydrogels as Theranostic Label-Free Magnetic Resonance Imaging Agents.
Lye Lin Lock (2017)
10.1021/jm401328u
Discovery of 5-substituted pyrrolo[2,3-d]pyrimidine antifolates as dual-acting inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis: implications of inhibiting 5-aminoimidazole-4-carbo
Shermaine Mitchell-Ryan (2013)
10.3892/OL.2012.773
Preclinical rationale for synergistic interaction of pemetrexed and cytotoxic nucleoside analogues.
T. Oguri (2012)
10.2147/PGPM.S3977
Tailoring treatment of nonsmall cell lung cancer by tissue type: role of pemetrexed
S. Powell (2009)
Identification of novel therapeutics for the treatment of MMR deficient tumours using high-throughput screens.
Delphine. Guillotin (2015)
Pemetrexed, A Modulator of AMP-activated Kinase Signaling and an Inhibitor of Wild type and Mutant p53
Stuti Agarwal (2015)
10.1592/phco.26.5.641
Pemetrexed, a Novel Antifolate Therapeutic Alternative for Cancer Chemotherapy
Leticia R. Villela (2006)
10.2174/1567201817666200210120231
Development of pemetrexed diacid-loaded Gelatin-Cloisite 30B (MMT) nanocomposite for improved oral efficacy against cancer: Characterization, In-vitro and Ex-vivo Assessment.
Kriti Soni (2020)
10.1038/nrclinonc.2014.51
Standing the test of time: targeting thymidylate biosynthesis in cancer therapy
P. Wilson (2014)
10.1385/MO:23:3:419
Pemetrexed-induced acute renal failure, nephrogenic diabetes insipidus, and renal tubular acidosis in a patient with non-small cell lung cancer
Vidya Vootukuru (2006)
10.1016/J.ANNDER.2013.01.406
Œedèmes inflammatoires et myosite
Hugo Cazenave (2013)
10.1186/s13256-017-1436-7
Unusually prolonged pemetrexed cytotoxicity in a patient with a lung adenocarcinoma: a case report
L. Sakhri (2017)
10.2147/CMAR.S150975
Efficacy and safety of pemetrexed and nedaplatin followed by pemetrexed maintenance therapy in advanced lung adenocarcinoma
Z. Lin (2017)
See more
Semantic Scholar Logo Some data provided by SemanticScholar