Pemetrexed Plus Cisplatin ""Makes a Difference"" in Mesothelioma Survival

By Megan Rauscher

NEW YORK Jul 21, 2003 (Reuters Health) - In a large phase III trial of patients with malignant pleural mesothelioma, the combination of pemetrexed plus cisplatin was associated with a statistically significant survival advantage over cisplatin alone, with manageable toxicity.

"For the first time we have a therapy for mesothelioma that makes a difference," Dr. Nicholas J. Vogelzang of the University of Chicago Cancer Research Center said in a university statement. 

In a telephone interview with Reuters Health Sunday he said, "Pemetrexed inhibits three enzymes necessary for DNA synthesis, in contrast to the first and second generation class of this drug which only inhibited one enzyme.  Plus it is retained within the cell for prolonged periods of time."

In the trial, reported in the July 15th Journal of Clinical Oncology, chemotherapy-naïve mesothelioma patients were randomly assigned to cisplatin 75 mg/m² alone (n=222) or with pemetrexed 500 mg/m² (n=226) given intravenously every 21 days.

Patients in the cisplatin/pemetrexed arm survived a median of 12.1 months compared with 9.3 months in the cisplatin-only arm.  The 2.8-month survival benefit represents a relative risk reduction for death of 23%. 

Median time to progression was 5.7 months in the cisplatin/pemetrexed arm versus 3.9 months in the cisplatin-only arm (P=0.001).  Response rates also favored the combination arm over the single-drug arm, 41.3% versus 16.7% (P<0.0001).

Of note, folic acid and vitamin B12 supplementation, instituted after 117 patients had enrolled, resulted in a significant reduction in toxicity in the cisplatin/pemetrexed arm without adversely affecting survival time.  Patients in the cisplatin-only arm also seemed to benefit from vitamin supplementation, but to a lesser degree.

Writing in an editorial, Dr. Valerie Rusch of Memorial Sloan-Kettering Cancer Center in New York says this trial "establishes pemetrexed and cisplatin as a new standard in systemic therapy for mesothelioma." 

"It is now reasonable to state," she continues, "that effective chemotherapy exists for MPM, dispelling the profound sense of nihilism surrounding treatment of this disease."

SOURCE:

• Journal of Clinical Oncology 2003;21:2629-2630,2636-2644.