Pemetrexed (Alimta) shows single-agent activity in advanced colorectal cancer. In two phase II studies in which patients received pemetrexed at 600 mg/m2 or 500 mg/m2 as first-line treatment for metastatic disease, objective response rates were 15.4% and 17.2%. In a National Surgical Adjuvant Breast and Bowel Project phase II trial in 54 patients with previously untreated advanced colorectal cancer, pemetrexed at 500 mg/m2 plus oxaliplatin (Eloxatin) at 120 mg/m2 every 21 days with folic acid/vitamin B12 supplementation resulted in an objective response of 23%.
It has also been combined with irinotecan and randmozed in first-line against Fofiri but did not do as well. Neither efficacy nor safety improved on the ALIRI arm compared to the FOLFIRI arm. Progression-free survival on FOLFIRI was significantly longer compared to ALIRI.
The issue is 2nd line therapy. As a single agent in second line, a study has been competed and results are awaited: A Trial of ALIMTA (Pemetrexed) Plus Irinotecan in Patients Who Have Been Previously Treated For Metastatic Colorectal Cancer, NCT00034502. This is a non-randomized study in patients who have received prior 5-FU therapy for colorectal cancer. The objective of this trial is to establish a maximum tolerated dose of ALIMTA and irinotecan given in combination as well as to assess the safety and efficacy of this combination for patients with locally advanced or metastatic colorectal cancer. ALIMTA and irinotecan will be given every 21 days.
F. Meriggi, B. Di Biasi, C. Caliolo, A. Zaniboni, The Potential Role of Pemetrexed in Gastrointestinal Cancer, Chemotherapy Vol. 54, No. 1, 2008
CHRISTOPHE LOUVET, Premetrexed in Advanced Colorectal Cancer ONCOLOGY. Vol. 18 No. 13 8
Craig Underhill et al, A Randomized Phase II Trial of Pemetrexed plus Irinotecan (ALIRI) versus Leucovorin-Modulated 5-FU plus Irinotecan (FOLFIRI) in First-Line Treatment of Locally Advanced or Metastatic Colorectal Cancer Oncology Vol. 73, No. 1-2, 2007