Raltitrexed - Oxaliplatin Combination Active In Malignant Mesothelioma

Combination of Raltitrexed and Oxaliplatin Is an Active Regimen in Malignant Mesothelioma: Results of a Phase II Study.

Journal of Clinical Oncology (JCO)

01/21/2003

By Elda Hauschildt

The combination of raltitrexed and oxaliplatin is an active regimen with an acceptable tolerability profile for outpatients with malignant mesothelioma.

Investigators from the department of medicine, Institute Gustave Roussy in Villejuif, France, say that haematological toxicity was mild and there was no alopecia among patients. Most common adverse events were asthenia, nausea/vomiting and paraesthesia. There were no treatment-related deaths.

Participants had diffuse malignant pleural mesothelioma. Fifteen pre-treated and 55 chemotherapy-naïve patients (median age 60 years) were enrolled in this open-label phase II study. Patients received raltitrexed at 3 milligrams/m(2), followed by oxaliplatin at 130 mg/m(2) every three weeks.

Overall, 14 patients (20%) demonstrated a partial response and 32 patients (46%) had stable disease. As well, 24 patients (34%) had a poor prognosis. Symptomatic response rates included: 36% for shortness of breath, 30% for pain, 23% for activity, 21% for appetite and 20% for asthenia.

The investigators say the median time to disease progression was 18 weeks.

Median survival was 31 weeks from the start of treatment and 49 weeks from mesothelioma diagnosis in chemotherapy-naive patients. In pre-treated patients, median survival was 44 weeks from treatment initiation and 226 weeks from diagnosis of mesothelioma.

One-year survival was 26% overall, 22% in chemotherapy-naïve patients and 40% in pre-treated patients.

Journal of Clinical Oncology, 2003; 21: 349-354

J Clin Oncol 2003 Jan 15;21(2):349-54

Purpose: The aim of this open-label phase II study was to evaluate the activity of raltitrexed (Tomudex; AstraZeneca, Cergy, France) and oxaliplatin combination therapy in patients with diffuse malignant pleural mesothelioma. Patients and Methods: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60 years; World Health Organization performance status of </= 2) were enrolled. Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m(2) followed by oxaliplatin 130 mg/m(2) every 3 weeks. Results: Twenty-four patients (34%) were classified as having a poor prognosis. In the overall study population, 14 patients (20%) had a partial response, and 32 patients (46%) had stable disease. The symptomatic response rates were as follows: shortness of breath, 36%; pain, 30%; activity, 23%; appetite, 21%; and asthenia, 20%. Median time to disease progression was 18 weeks (95% confidence interval [CI], 13 to 22 weeks). In chemotherapy-naive patients, median survival was 31 weeks (95% CI, 23 to 40 weeks) from the start of treatment and 49 weeks (95% CI, 40 to 52 weeks) from diagnosis of mesothelioma. In pretreated patients, median survival was 44 weeks (95% CI, 24 to 40 weeks) from the start of treatment and 226 weeks (95% CI, 63 to 292 weeks) from the diagnosis of mesothelioma. Overall 1-year survival was 26% (95% CI, 15.5% to 36.4%), survival was 22% (95% CI, 10.9% to 33.2%) in chemotherapy-naive patients and 40% (95% CI, 15.2% to 64.8%) in pretreated patients. Hematologic toxicity was mild, and there was no alopecia. The most common adverse events were asthenia, nausea/vomiting, and paraesthesia, and no treatment-related deaths were reported. Conclusion: The raltitrexed and oxaliplatin combination is an active outpatient regimen in malignant mesothelioma and has an acceptable tolerability profile.

PMID: 12525529 [PubMed - in process]

** POSTED JANUARY 23, 2003 **