Multicenter non-randomized phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients

Background: This multicenter, phase II, open-label study evaluated the antitumor efficacy and safety of oxaliplatin and raltitrexed (Tomudex) in non-pretreated advanced colorectal cancer patients. Patients and methods: Seventy-one patients received oxaliplatin 130 mg/m(2) and raltitrexed 3 mg/m(2) intravenously on an outpatient basis every 3 weeks. All patients had histologically proven metastatic colorectal adenocarcinoma, performance status less than or equal to2 and good baseline organ function. Most (56%) had only one disease site. All patients were assessed for safety, and 66 of 69 eligible patients were assessed for response. Results: A total of 404 cycles were administered, with a median of six cycles per patient (range 1-12 cycles). Relative dose intensities were 0.98 and 0.98 for oxaliplatin and raltitrexed, respectively. The most common grade 3-4 toxicities (National Cancer Institute Common Toxicity Criteria) among treated patients were as follows: neutropenia (21 patients, 30%), asthenia (eight, 11%), diarrhea ( 12, 17%), liver function test abnormalities (24, 34%), nausea (nine, 13%) and vomiting (nine, 13%). Two treatment-related deaths occurred (hematotoxicity in one patient and gastrointestinal toxicity in the other) and two further deaths were possibly related to treatment (hepatic dysfunction in one patient and neuropathy in the other). Thirty-seven objective responses (one complete) were obtained [objective response rate 54%; 95% confidence interval (CI) 42% to 65%] in eligible patients. The median response duration was 8.5 months (95% CI 6.7-12.2 months), while median progression-free and overall survival among eligible patients were 6.2 (95% Cl 5.1-6.9 months) and 14.6 months (95% Cl 11.0-18.9 months), respectively. Conclusions: The present study confirms the feasibility of the raltitrexed plus oxaliplatin combination and its activity in non-pretreated advanced colorectal cancer patients.