Phase II study of pemetrexed disodium, a multitargeted antifolate, and cisplatin as first-line therapy in patients with advanced nonsmall cell lung carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group.

摘要: BACKGROUND Pemetrexed disodium (Alimta [Eli Lilly and Company, Indianapolis, IN], LY231514, multitargeted antifolate) is a new antifolate agent that inhibits multiple enzymes in the folate pathway. Phase II trials showed single-agent response rates of 16% 23% untreated patients with nonsmall cell lung carcinoma (NSCLC). This study was undertaken to determine pemetrexed given combination cisplatin. METHODS Previously were eligible if they had Stage IIIB or IV NSCLC, performance status 0, 1, 2, adequate hematology biochemistry bidimensionally measurable lesions. Patients brain metastases neuropathy higher than Grade 2 excluded. Pemetrexed 500 mg/m2 over 10 minutes, cisplatin 75 hydration mannitol diuresis administered on Day 1 each 21-day cycle. Dexamethasone 4 mg taken orally once every 12 hours starting 24 before treatment continuing for 6 doses after treatment. Four detailed pharmacokinetic analysis performed. RESULTS Between May 1998 June 1999, 31 treated study. There 20 males 11 females; median age 60 years (range, 35–75 years); there 5 IIIB, 26 IV, 0 2. In 29 evaluable response, 13 partial responses (PRs; overall rate [ORR], 95%; confidence interval [CI]: 26–64%) duration 6.1 months (1.6–7.8 months). Three four achieved PR, responded (ORR, 45.8% IV). Eighteen died. The survival 8.9 1–15+ A total 160 courses delivered (median, both disodium). 3 anemia observed patients, respectively, granulocytopenia 7 respectively. nausea emesis occurred only 3/4 diarrhea motor neuropathy. Nine infections, one case febrile neutropenia. Pharmacokinetic results Cmax, clearance Vss values be similar data from same dose. CONCLUSIONS The active against advanced NSCLC well-tolerated convenient outpatient regimen. It deserves further compare it other standard regimens NSCLC. Cancer 2001;92:595–600. © 2001 American Society.