30 patients with advanced colorectal cancer will be enrolled to observe the efficacy and safety of raltitrexed combined with apatinib as a third-line treatment.

In this study, we plan to enroll 30 patients with advanced colorectal cancer after failure of second-line standard chemotherapy. The therapeutic regimen is raltitrexed, 3 mg/㎡, ivgtt, d1, apatinib 500 mg, qd,po, d1-21, Every 3 weeks for 1 cycles, the primary end point was PFS, the secondary end point was OS, DCR, ORR etc. Aim to observe the efficacy and safety of raltitrexed combined with apatinib as a third-line treatment of in patients with advanced colorectal cancer.

Inclusion Criteria:

• 1.Male or female, ≥ 18 of age;

• 2.Histological confirmed advanced colorectal adenocarcinoma，and at least one measurable lesion;

• 3.Have failed for ≥ 2 lines of standard chemotherapy(included Fluorouracil, irinotecan and oxaliplatin);

• 4.ECOG performance status 0-2;

• 5.Life expectancy of more than 3 months;

• 6.The main organs function is well, and randomized within 14 days before the relevant inspection indicators to meet the following requirements:

  1. blood routine test Hgb ﹥90g/L, ANC﹥1.5×109/L, Platelets ﹥ 100×109/L,
  2. biochemical tests Serum Total bilirubin ≤ 1.5 X UNL(upper normal limit), ALT or AST ≤ 2 xUNL, and ﹤ 5 x UNL（Hematogenous metastases）, Creatinine clearance rate≥ 60 ml/min(Cockcroft-Gault formula),
  3. Doppler echocardiography assessment：LVEF ≥ 50%;

• 7.No serious heart, lung, liver, kidney dysfunction; no jaundice and gastrointestinal obstruction; no acute infection;

• 8.Signed informed consent;

• 9.Good compliance, and family members agree to receive survival follow-up.

Exclusion Criteria:

• 1.Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);