ASCO: Study Confirms Pemetrexed-Platinum Activity in Malignant Mesothelioma

June 6, 2007

CHICAGO -- Confirming results of earlier studies, pemetrexed combined with either cisplatin or carboplatin demonstrated activity in previously untreated malignant pleural mesothelioma, said researchers here.

CHICAGO, June 6 -- Confirming results of earlier studies, pemetrexed combined with either cisplatin or carboplatin demonstrated activity in previously untreated malignant pleural mesothelioma, said researchers here.

Treatment with a pemetrexed-cisplatin doublet led to an overall response rate of 26.3% in 745 mesothelioma patients, and the combination of pemetrexed and carboplatin was associated with an overall response rate of 21.6%, found Armando Santoro, M.D., of the Instituto Clinico Humanitas in Milan, Italy, and colleagues.

One-year survival was 63 to 64% with both regimens, Dr. Santoro reported at the American Society of Clinical Oncology meeting.

The median time to progression was about seven months with both regimens, he said. None of the differences was statistically significant.

Somewhat surprisingly, said Dr. Santoro, the carboplatin doublet caused more toxicity, but he feels that pemetrexed-carboplatin remains a better option for elderly patients and others with increased susceptibility to chemotherapy's toxicity.

The researchers findings came from an analysis of outcome data on 1,704 chemotherapy-nave malignant pleural mesothelioma patients, including 1,497 patients with response data. They were among more than 3,000 mesothelioma patients worldwide who received pemetrexed alone or in combination with a platinum agent under the pemetrexed expanded access program, said Dr. Santoro.

All the patients had unresectable disease. They received pemetrexed at a dose of 500 mg/m2 by 10-minute intravenous infusion, followed by cisplatin 75 mg/m2 or carboplatin AUC 5. The chemotherapy regimen was repeated ever 21 days. Patients treated with pemetrexed-cisplatin received a median of five cycles of therapy, compared with six cycles for the pemetrexed-carboplatin regimen.

The cisplatin regimen resulted in 15 complete responses (2%) and 181 partial responses (24.3%) among 745 patients. Among 752 patients who received carboplatin, seven (0.9%) had complete responses and 156 (20.7%) had partial responses, leading to an overall response rate of 21.6%.

Stable disease was observed in 51.4% of cisplatin-treated patients and 54.1% of patients treated with carboplatin. The disease control rate (CR + PR + SD) was 77.7% with cisplatin and 75.8% with carboplatin.

Grade 3-4 hematologic toxicity was greater with the pemetrexed-carboplatin doublet, including:

  • Neutropenia, 36.1% versus 23.9%
  • Leukopenia, 21% versus 13.1%
  • Anemia, 14.3% versus 7.2%
  • Thrombocytopenia, 14.3% versus 5%

"The important point of this study is the two combinations demonstrated similar activity," said Dr. Santoro. "That means physicians can choose the regimen they consider most appropriate for an individual patient with malignant pleural mesothelioma without sacrificing efficacy."