COX-2 Inhibitor May Boost Cancer Treatment
July 17, 2003, Acurian

Source: New York Weill Cornell Medical Center


For the first time it has been shown that a COX-2 inhibitor may
boost the effectiveness of chemotherapy in the treatment of cancer,
according to a study by physician-scientists at New York Weill
Cornell Medical Center. The new study, which looks at Non-Small Cell
Lung Cancer (NSCLC), represents the latest of numerous Weill Cornell
research findings suggesting the benefits of COX-2 inhibitors for
treatments of cancer and pre-cancerous conditions of the lung, colon,
breast, esophagus, mouth, and bladder. NSCLC is the most aggressive
type of lung cancer and the leading cause of cancer death in the U.S.

The new study, published in the current issue of the Journal of
Clinical Oncology, finds that patients with NSCLC treated with
celecoxib, a COX-2 inhibitor, administered in conjunction with
paclitaxel and carboplatin, two common chemotherapeutic agents,
results in lower levels of intratumoral prostaglandin E2 (PGE2), a
molecule associated with tumor growth, when compared to treatment
with chemotherapy alone. Additionally, the treatment is shown to be
feasible and safe.

"This study shows that celecoxib, by decreasing COX-2-derived PGE2,
may be useful when given in combination with chemotherapy," said Dr.
Nasser Altorki, the study's principal investigator, Professor of
Cardiothoracic Surgery at Weill Cornell Medical College, and Director
of the Division of Thoracic Surgery at New York Weill Cornell Medical
Center. "Remarkably, for patients taking celecoxib, the amount of
PGE2 present in the tumor was equivalent to amounts in a non-
cancerous lung."

During the Phase II trial, 29 patients with stages IB to IIIA NSCLC
were treated with two preoperative cycles of paclitaxel and
carboplatin, along with daily doses of 800 mg of celecoxib, followed
by surgical resection of the tumor. Levels of PGE2 in the primary
tumors and adjacent normal lung tissue were compared with 13 control
patients, who received paclitaxel and carboplatin without celecoxib.
Overall clinical response rate was 65 percent.

An upcoming multicenter Phase II trial led by Dr. Altorki will
examine changes in tumor size and survival rates for NSCLC patients
treated with chemotherapy alone vs. chemotherapy plus a COX-2
inhibitor (celecoxib).

Cyclooxygenase-2 (COX-2) is an enzyme that catalyzes the synthesis of
prostaglandins (PGs). Increased levels of COX-2 and PGs have been
observed in a variety of malignancies including NSCLC. PGE2, a
downstream product of COX-2, can promote tumor growth by stimulating
angiogenesis and invasiveness, as well as inhibiting apoptosis (cell
death) and immune surveillance. Additionally, higher-than-normal
quantities of COX-2 may unfavorably alter the response of malignant
cells to cytotoxic therapy. Similarly, paclitaxel treatment induces
high quantities of COX-2.

The study was supported by a grant from Pharmacia Oncology and
Pfizer. Preliminary results were first presented at the annual
meeting of the American Society of Clinical Oncology in April 2002.

The study is co-authored by Dr. Andrew Dannenberg, Co-Director of
NewYork-Presbyterian Hospital's Cancer Prevention Program and the
Henry R. Erle-Roberts Family Professor of Medicine at Weill Cornell
Medical College. Contributing authors from NewYork Weill Cornell
Medical Center include Dr. David Yankelevitz, Dr. Kotha Subbaramaiah,
Dr. Jeffrey Port, Dr. Roger Keresztes, Dr. Robert Korst, Dr. Douglas
Flieder, Dr. Daniel Libby, Dr. Mark Pasmantier, and Cathy Ferrara,
R.N.

New York Weill Cornell's COX-2 Anti-Cancer Research

For the last decade, NewYork Weill Cornell's Dr. Andrew Dannenberg
has led research on the use of COX-2 inhibitors for a range of cancer
and pre-cancerous conditions. Ongoing research is evaluating the
potential utility of selective COX-2 inhibitors in conditions
including:


Pre-cancerous adenomatous polyps of the colon
Basal cell (skin) carcinomas in patients with the nevoid basal cell
carcinoma syndrome
Barrett's esophagus, a pre-cancerous condition of the esophagus
Non-small-cell lung cancer
Oral pre-malignant lesions, white and red patches in the oral cavity
that are commonly caused by tobacco and alcohol use
Cancer of the bladder
Other investigations are studying how dietary constituents that
inhibit COX-2 -- such as resveratrol (found in red wine and the skin
of red grapes), and omega-3 fatty acids (found in fish like salmon) --
can prevent cancer.

Celecoxib and COX-2

Studies have shown that levels of COX-2 are markedly elevated in many
different types of cancer versus adjacent normal tissue. Celecoxib,
an anti-inflammatory drug commonly used to treat arthritis, has been
shown to inhibit COX-2, and in turn, reduce the formation, growth and
metastasis of several types of experimental cancers. Celecoxib also
has been shown to suppress angiogenesis, the process by which tumors
create new blood vessels needed to obtain nutrients for their growth
and spread.

Additionally, because standard cancer therapies like chemotherapy and
radiation induce COX-2, selective COX-2 inhibitors such as Celecoxib
may prove useful as a supplemental, or adjuvant, therapy. In 1999,
the drug was approved by the FDA for use to reduce the number of
polyps in familial adenomatous polyposis (FAP), a rare and
devastating genetic condition that results in colorectal cancer.


Copyright © 2003 Acurian Inc. All Rights Reserved.

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