Pemetrexed in pancreatic cancer.
Single-agent gemcitabine (Gemzar) is the standard of chemotherapy for advanced pancreatic cancer, with no phase III trials to date having shown significantly improved survival with gemcitabine-based combinations vs single-agent treatment. The multitargeted antifolate agent pemetrexed (Alimta) shows synergistic effects in vitro in combination with gemcitabine, and activity and good tolerability when used as single-agent treatment in advanced pancreatic cancer. In a phase II trial in patients with advanced pancreatic cancer, the combination of gemcitabine at 1,250 mg/m2 on days 1 and 8 plus pemetrexed at 500 mg/m2 on day 8 after gemcitabine every 21 days resulted in a median survival of 6.5 months and a 1-year survival rate of 29%. Neutropenia was the primary toxicity, with grade 4 toxicity in 51% of patients. The promising results of this trial prompted the initiation of a phase III trial comparing gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 every 28 days vs the 21-day gemcitabine/pemetrexed regimen given with vitamin supplementation in patients with pancreatic cancer. The primary outcome measure was overall survival, with secondary measures including response rate, progression-free survival, and quality of life. While an increase in response and time to progression was reported for the gemcitabine/pemetrexed combination, there were no significant differences in survival between treatment arms.
Seitz
Jean-François
JF
C.H.U. la Timone and Université de la Méditerranée Marseille, France. jseitz@mail.ap-hm.fr
Dahan
Laetitia
L
Ries
Pauline
P
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005493:Folic Acid Antagonists / Q000008:administration & dosage*; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068437:Pemetrexed; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D000093542:Gemcitabine
D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D013940:Thymidylate Synthase; D000093542:Gemcitabine