Review of a promising new agent—pemetrexed disodium

• Published in: Cancer Vol. 97; no. S8; pp. 2056 - 2063
• Main Authors: Paz‐Ares, Luis, Bezares, Susana, Tabernero, José M., Castellanos, Daniel, Cortes‐Funes, Hernán
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 15-04-2003; Wiley-Liss
• Subjects: Animals; antifolate antimetabolite; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Clinical Trials as Topic; Glutamates - adverse effects; Glutamates - therapeutic use; Guanine - adverse effects; Guanine - analogs & derivatives; Guanine - therapeutic use; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Medical sciences; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - mortality; Pemetrexed; Pharmacology. Drug treatments; purine synthesis; pyrimidine synthesis; Safety; Survival Rate; thymidylate synthase; Thymidylate Synthase - antagonists & inhibitors; Treatment Outcome; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - mortality; Antineoplastic agent; Preclinical trial; Review; Antifolate; Urinary bladder; Phase II trial; Human; Drug combination; Urinary system disease; Enzyme; Transferases; Enzyme inhibitor; antifolate antimetabolite; pyrimidine synthesis; Urinary tract disease; Malignant tumor; purine synthesis; Thymidylate synthase; Pemetrexed; Chemotherapy; Treatment; Methyltransferases; Antimetabolic; Animal; Phase I trial; Bladder disease
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.11279

Pemetrexed disodium (ALIMTa™, [pemetrexed], LY231514; Eli Lilly and Company; Indianapolis, IN), a novel antifolate antimetabolite with multiple enzyme targets involved in both pyrimidine and purine synthesis, has entered clinical trials due to its favorable pleclinical profile. Many studies utilizing the drug, as a single or combination agent, are currently ongoing, including Phase III trials in mesothelioma, nonsmall cell lung carcinoma (NSCLC) and pancreatic cancer. Promising feasibility and activity data have been obtained with pemetrexed in combination with platinum compounds and gemcitabine. The supplementation with daily oral folate could reduce the incidence of hematologic toxicities while preserving the antitumor activity of pemetrexed. Cancer 2003;97(8 Suppl):2056–63. © 2003 American Cancer Society.
DOI 10.1002/cncr.11279
The authors review results from numerous studies with pemetrexed disodium, which is a novel antifolate antimetabolite. Phase I–III trials, combination studies, and studies in patients with bladder cancer are described. Pemetrexed disodium exhibited significant antitumor activity in a wide range of solid tumors, including bladder cancer.