Malignant pleural mesothelioma is an aggressive cancer of the lining of the lung. The disease occurs typically 20 to 40 years after exposure to asbestos. Each year, there are approximately 2,500 new cases in the United States and 5,000 new cases in the European Union. Experts expect incidence of this disease to increase over the next 2 decades.

Mesothelioma survival is short, and the disease causes severe chest pain, chronic shortness of breath, and sense of hopelessness. There is no effective or approved chemotherapy for mesothelioma. Pemetrexed (Alimta) has emerged as a potentially effective drug in Phase I clinical trials.

This novel antifolate drug exhibited a 14% response rate as a single agent in this disease. Subsequently, investigators conducted a phase III trial of pemetrexed (500 mg/m²) and cisplatin (75 mg/m²) versus cisplatin alone.

The primary endpoint of the phase III trial was survival. Secondary endpoints included response rate, quality of life and lung function. 452 patients were enrolled, of which 448 had eligibility for the final analysis.

In this ASCO presentation, Dr. Vogelzang reported a 25% increase in survival with pemetrexed and cisplatin. (P = 0.02). Patients on the combination had a survival of approximately one year, versus nine months for the cisplatin arm.

This is the first time investigators have ever documented an improvement in mesothelioma survival.

The tumor response rate was 41% for pemetrexed-cisplatin treatment versus 17% for cisplatin. Median time to disease progression was 5.7 months versus 3.9 months in the cisplatin arm.

Another important factor was symptom improvement. Two independent measures of lung function showed improvement. For example, vital capacity gradually improved on the experimental treatment, while it declined on the comparison arm. Pain on a symptom scale for lung cancer improved greatly with pemetrexed therapy, and worsened on cisplatin alone.

During the trial, investigators noted a high rate of toxicity in the pemetrexed-cisplatin arm. This was linked to elevated homocysteine. Subsequently enrolled patients received folic acid and vitamin B₁₂ in addition to the experimental treatment. For patients who received this simple vitamin supplementation regimen, toxicity and drug-related death rate decreased and were virtually identical in both treatment arms.

(abstract #5)