Clinical Observation Of Raltitrexed-based Versus FOLFIRI In The Second-line Treatment Of Advanced Colorectal Cancer

Objective To evaluate the efficacy and safety of raltitrexed combined oxaliplatin or Irinotecan versus FOLFIRI in the second-line treatment of advanced colorectal cancer.Material and Methods The target opulation were patients with advanced colorectal cancer who progressed after first-line chemotherapy of FOLFOX4 or FOLFOX6. The patients are divided into three group:Group A: Treatment consisted of Irinotecan 180 mg/m2 as a90-minute intravenous infusion followed 2 hours later by raltitrexed 3 mg/m2 as a15-minute intravenous infusion on Day 1, repeated every 3 weeks until further disease progression, unacceptable toxicity or the decision of the patient. Group B:Treatment consisted of raltitrexed 3 mg/m2 as a 15-minute intravenous infusion followed 45 minutes later by oxaliplatin 130 mg/m2 as a 2h intravenous infusion on Day 1, repeated every 3 weeks until further disease progression, unacceptable toxicityor the decision of the patient. Control group: Treatment consisted of5-fluorouracil(5-FU) 400mg/m2 as a 2h intravenous infusion on Day 1 and2400mg/m2 as a 46 h intravenous infusion followed by Irinotecan 150 mg/m2 as a90-minute intravenous infusion and Leucovorin Calcium 200 mg/m2 as a 2h intravenous infusion on Day 1, repeated every 2 weeks until further disease progression, unacceptable toxicity or the decision of the patient. The patients in group A and group B were planned to receive at least 6 cycles of chemotherapy. And the patients in control group were planned to receive at least 12 cycles of chemotherapy. They were assessed on the basis of WHO evaluation standard of objective therapeutic effect for solid tumor after 45 days.Results94 patients were all assessable to observe the efficacy and safety. In the group A,no case was CR. 4 case were PR, response rate was 18.2%. 6 case were SD, response rate was 27.2%. 12 case were PD, response rate was 54.6%. Median time to progression(TTP) were 6.2 months. Median overall survival(OS) was 14.6 months.In the group B, no case was CR. 5 case were PR, response rate was 20.0%. 11 case were SD, response rate was 44.0%. 9 case were PD, response rate was 36.0%.Median time to progression(TTP) were 6.6 months. Median overall survival was14.8 months. In the control group, no case was CR. 6 case were PR, response rate was 12.7%. 11 case were SD, response rate was 23.4%. 30 case were PD, response rate was 63.8%. Median time to progression(TTP) were 3.8 months. Median overall survival was 9.9 months. The response rate(RR) of the three group were:18.2%、20.0%、RR 12.7%(Group A and group B are higher than control group P=0.690).The disease control rate(DCR) of the three group were:45.4%、64.0%、36.2%(Group A and group B are higher than control group P=0.078). Toxicity of the three group were leukopenia(59.0%、60.0%、72.3%)、vomiting(45.4%、40.0%、55.3%)、diarrhea(36.4% 、 8.0% 、 44.7%) 、 thrombocytopenia(18.2% 、 8.0% 、 38.3%) 、mucositis(4.5%、12%、31.9%)、peripheral neurotoxici(0、52.0%、27.7%)、liver injury(22.7%、28.0%、19.1%)、hypodynamia(86.4%、68.0%、89.3%). Most of thetoxicity were grade I-II, the rate of grade III-IV toxicity waslow.Conclusions Raltitrexed combined irinotican or oxaliplatin is effective for second-line treatment of advanced colorectal cancer. They have lower toxicity compared with FOLFIRI regimen. So raltitrexed-based chemotherapy can be used as safe and effective second-line treatment for patients who used FOLFOX4 or FOLFOX6 as first-line therapy resulted in treatment failure.