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Research on Malignant Mesothelioma on Upswing

Research on Malignant Mesothelioma on Upswing

NEW YORK—"In 2002 there is a lot of activity in mesothelioma
research," Nicholas J. Vogelzang, director, University of Chicago Cancer
Research Center, said at a media briefing on malignant mesothelioma, sponsored
by the American College of Preventive Medicine. "This was an orphan
disease for many years." Roman Perez-Soler, MD, of Albert Einstein College
of Medicine, added: "We’re moving from empiricism to rational
therapies."

Said Dr. Vogelzang: "Many people did not believe that chemotherapy
worked," Today, he said, new active drugs are having modest but real
effects. 

The only potential cure remains extrapleural pneumonectomy. With this
operation, which removes the lung, diaphragm, and pericardial sac, 5-year
survival is about 15%, Dr. Perez-Soler said. Without it, no one survives, Dr.
Vogelzang said. Most cases are advanced at diagnosis, he added, and not
surgically treatable. "Radiation therapy can be used," he said,
"but rarely eliminates the cancer. It can prevent the cancer from
spreading outside the chest wall, and this is primarily what it’s used
for."

Given the site of malignant mesothelioma in the pleura and visceral walls,
one rational approach would be intra-cavity drug administration, Dr. Perez-Soler
said. Several agents, including L-NDDP (a liposomal formulation of a cisplatin analog), developed in his
laboratory, have been tried this way with good results. Most patients, however,
he said, "are not eligible for this because when they present, the tumor
is too thick, and the penetration of the drug from inside the cavity into the
wall is suboptimal." The same is true for photodynamic therapy.

The most promising systemic chemotherapeutics, Dr. Perez-Soler said, are the
antifolates, anthracyclines, and platinums. In trials of antifolates such as
methotrexate, he noted, 18% of patients had significant tumor reductions. Dr.
Perez-Soler called Eli Lilly’s investigational agent pemetrexed "a
better methotrexate" because it targets three key enzymes in the cancer
pathway rather than two.

Responses to the anthracycline doxorubicin averaged 12% and to cisplatin
(Platinol), 13%. Taxanes and camptothecins have not proven effective, Dr.
Perez-Soler said. With cisplatin-based combinations, the response rate is about
20%. An Australian trial of cisplatin-gemcitabine (Gemzar) using different
criteria than in US studies recorded a 47% positive response rate, he noted,
and a median survival of 9.5 months.

Dr. Vogelzang and his colleagues have defined six categories of the disease
based on patient characteristics. In the group with the poorest prognosis,
median survival is 1.4 months; in the group with the best prognosis, it is 13.9
months.

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