HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study.

AbstractBACKGROUND:
Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed-an antifolate antineoplastic agent-in patients with advanced non-small-cell lung cancer. We assessed pemetrexed as maintenance therapy in patients with this disease.
METHODS:
This randomised double-blind study was undertaken in 83 centres in 20 countries. 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m(2), day 1) plus best supportive care (n=441) or placebo plus best supportive care (n=222) in 21-day cycles until disease progression. Treatment was randomised with the Simon and Pocock minimisation method. Patients and investigators were masked to treatment. All patients received vitamin B(12), folic acid, and dexamethasone. The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00102804.
FINDINGS:
All randomly assigned participants were analysed. Pemetrexed significantly improved progression-free survival (4.3 months [95% CI 4.1-4.7] vs 2.6 months [1.7-2.8]; hazard ratio [HR] 0.50, 95% CI 0.42-0.61, p<0.0001) and overall survival (13.4 months [11.9-15.9] vs 10.6 months [8.7-12.0]; HR 0.79, 0.65-0.95, p=0.012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0.0001), specifically fatigue (22 [5%] vs one [1%], p=0.001) and neutropenia (13 [3%] vs 0, p=0.006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]; p=0.0001).
INTERPRETATION:
Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer.
FUNDING:
Eli Lilly.
AuthorsTudor Ciuleanu, Thomas Brodowicz, Christoph Zielinski, Joo Hang Kim, Maciej Krzakowski, Eckart Laack, Yi-Long Wu, Isabel Bover, Stephen Begbie, Valentina Tzekova, Branka Cucevic, Jose Rodrigues Pereira, Sung Hyun Yang, Jayaprakash Madhavan, Katherine P Sugarman, Patrick Peterson, William J John, Kurt Krejcy, Chandra P Belani
JournalLancet (London, England) (Lancet) Vol. 374 Issue 9699 Pg. 1432-40 (Oct 24 2009) ISSN: 1474-547X [Electronic] England
PMID19767093 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Guanine
Topics
  • Aged
  • Antineoplastic Agents (adverse effects, therapeutic use)
  • Carcinoma, Non-Small-Cell Lung (diagnosis, drug therapy, mortality)
  • Disease-Free Survival
  • Double-Blind Method
  • Fatigue (chemically induced)
  • Female
  • Glutamates (adverse effects, therapeutic use)
  • Guanine (adverse effects, analogs & derivatives, therapeutic use)
  • Humans
  • Lung Neoplasms (diagnosis, drug therapy, mortality)
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neutropenia (chemically induced)
  • Pemetrexed
  • Prognosis
  • Proportional Hazards Models
  • Survival Rate
  • Treatment Outcome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: