Combination of raltitrexed and oxaliplatin is an active regimen in malignant mesothelioma: results of a phase II study.

Abstract

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. PATIENT AND METHODSs: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60 years; World Health Organization performance status of < or = 2) were enrolled. Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m2 followed by oxaliplatin 130 mg/m2 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.

• Authors: K Fizazi, H Doubre, T Le Chevalier, A Riviere, J Viala, C Daniel, L Robert, P Barthélemy, A Fandi, P Ruffié
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 21 Issue 2 Pg. 349-54 (Jan 15 2003) ISSN: 0732-183X [Print] United States
• PMID: 12525529 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Organoplatinum Compounds
• Quinazolines
• Thiophenes
• Oxaliplatin
• raltitrexed

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Disease Progression
• Dose-Response Relationship, Drug
• Female
• Gastrointestinal Diseases (chemically induced)
• Hematologic Diseases (chemically induced)
• Humans
• Male
• Mesothelioma (drug therapy, pathology)
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Peritoneal Neoplasms (drug therapy, pathology)
• Pleural Neoplasms (drug therapy, pathology)
• Prognosis
• Quinazolines (administration & dosage)
• Survival Rate
• Thiophenes (administration & dosage)
• Treatment Outcome