The articles in this supplement to ONCOLOGY, "Clinical Update on
Pemetrexed," are presented by leading international clinical and
preclinical investigators in the arenas of thoracic, gastrointestinal, breast, and
gynecologic cancers. They cover a wide range of topics that focus on the promising
agent pemetrexed (Alimta).
Pemetrexed is a novel folate antimetabolite that inhibits thymidylate synthase,
dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase, all of
which are involved in pyrimidine and purine synthesis, resulting in impeded synthesis
of the nucleotide precursors of DNA and RNA. This agent has demonstrated activity in
clinical trials in a variety of tumor types, such as those presented herein.
In February 2004, the US Food and Drug Administration (FDA) approved
pemetrexed-in combination with cisplatin, a commonly used chemotherapy agent-
for use in the treatment of malignant pleural mesothelioma, a devastating cancer often
associated with asbestos exposure. In July 2004, The Oncologic Drugs Advisory
Committee (ODAC) of the FDA positively endorsed pemetrexed for accelerated
approval as monotherapy in the second-line treatment of non-small-cell lung cancer.
The topics in this volume include the biochemical pharmacology of pemetrexed,
preclinical/phase I studies, and phase II and III studies in thoracic (non-
small-cell lung cancer and mesothelioma), gastrointestinal (pancreas, bladder,
colorectal, and gastric), breast, and gynecologic cancers. Moreover, data from
current and future pharmacogenomics and translational research with pemetrexed
and gemcitabine (Gemzar) are presented. In addition to presenting current trial data
in this volume, the authors present information on clinical trends and the design of
future trials focusing on pemetrexed, either as a single agent or in combination.
Finally, an additional goal was to produce enduring material for investigators
to aid them in current and future study. Therefore, the material contained in this
volume is intended to be a thorough, objective, balanced presentation of clinical and
preclinical research with pemetrexed in multiple tumor types. I hope that you, the
reader, find the data and information to be stimulating, timely, and useful in patient
management and/or the design of clinical trials.