Raltitrexed plus oxaliplatin as first-line chemotherapy in metastatic colorectal carcinoma: a multicentric phase II trial

Abstract

For advanced colorectal carcinoma, two new drugs, raltitrexed (TOM) and oxaliplatin (L-OHP), have recently shown interesting results. Preclinical and clinical studies suggest that this combination, because of its favorable toxicity profile, high response rate and convenient schedule of administration, can be administered successfully in this disease. In our phase II study, 37 non pre-treated patients with metastatic colorectal carcinoma were treated with TOM (3 mg/m(2)) and L-OHP (130 mg/m(2)) every 3 weeks. In total, 222 cycles were administered; all patients received at least 2 cycles (median 6, range 2-8). There were two complete and 14 partial responses for an overall response rate of 43% (95% CI 27-69%). The median time to response was 2.5 months (range 2-4) and the median duration was 10.3 months (range 5-18). Twelve of the 23 (52%) patients with symptomatic colorectal cancer were classified as clinical benefit responders for at least 4 weeks during the study period. Treatment was well tolerated, and both acute, essentially hematologic, and cumulative hepatic and neurologic toxicities were manageable and reversible. Response rate and toxic effects observed during this study warrant additional studies comparing this TOM-L-OHP regimen with CPT-11 and/or capacitebine-containing regimens in metastatic colorectal carcinoma.

First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer

“…In contrast with previous favorable reports on the combination of raltitrexed plus oxaliplatin in first-line treatment of advanced CRC [5,6,7,8], the results of the present study with raltitrexed plus CPT-11 show a suboptimal response rate and a limited median overall patient survival that arises the question of its actual efficacy. These figures also compare unfavorably with the more standard combinations of 5-FU plus CPT-11 [1, 22] or 5-FU plus oxaliplatin [2].…”

“…However, raltitrexed combinations have already been explored in this context. In phase II trials, raltitrexed plus oxaliplatin has shown a consistent activity in patients with previously untreated, advanced CRC (43–54% response rate) [5,6,7,8]. Preclinical data suggest a synergistic activity between CPT-11 and raltitrexed and three recent phase I studies have shown that single-agent full doses of both drugs can be safely given thrice-weekly [9,10,11].…”

A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer

“…On the basis of the predefined eligibility criteria, we selected 12 studies [3][4][5][7][8][9][10][11][12][13][14][15] that fulfilled the qualitative and quantitative requirements of the systematic analysis. A total of 735 patients were enrolled across the selected trials (range, 37-94).…”

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

“…Subsequent phase II studies have attempted to define the activity of raltitrexed in combination with other agents in colorectal cancer. One of the most active doublets is an oxaliplatin combination, and in 6 separate studies (Table 14 [219][220][221][222][223][224]), response rates of between 43 and 62% were obtained in a frontline setting. Activity drops to between 16 and 33% in previously treated patients (Table 15 […”