Raltitrexed-based chemotherapy for advanced colorectal cancer

Clin Res Hepatol Gastroenterol. 2014 Apr;38(2):219-25. doi: 10.1016/j.clinre.2013.11.006. Epub 2013 Dec 30.

Abstract

Aims: To evaluate the efficiency and safety profile of raltitrexed-based chemotherapy in the treatment of advanced colorectal cancer.

Methods: An electronic search was undertaken to identify randomized controlled trials comparing raltitrexed-based regimen to 5-fluorouracil-based regimen in patients with advanced colorectal cancer. The outcomes included overall survival, overall response rate and toxicities.

Results: This meta-analysis included 11 studies with 4622 patients. Overall, there were no significant differences between the two regimens in terms of overall survival (HR=1.06, 95% CI: 0.96-1.17, P=0.23) or overall response rate (RR=1.09, 95% CI: 0.86-1.38, P=0.47). In subgroup analysis, patients in raltitrexed/oxaliplatin group had significantly higher partial response (RR=1.53, 95% CI: 1.17-2.00, P=0.002), overall response rate (RR=1.42, 95% CI: 1.10-1.82, P=0.006), disease control rate (RR=1.16, 95% CI: 1.04-1.29, P=0.009) and lower progressive disease (RR=0.61, 95% CI: 0.45-0.84, P=0.002) when compared to 5-fluorouracil/leucovorin/oxaliplatin group. Occurrence of severe anemia (RR=2.23, 95% CI: 1.38-3.59, P=0.0001), asthenia (RR=2.29, 95% CI: 1.36-3.84, P=0.002), hepatic disorders (RR=7.51, 95% CI: 1.30-43.56, P=0.02), and nausea/vomit (RR=1.70, 95% CI: 1.03-2.81, P=0.04) were significantly higher with the raltitrexed arm treatment, while frequencies of grade 3/4 alopecia (RR=0.36, 95% CI: 0.26-0.50, P<0.00001) and stomatitis/mucositis (RR=0.14, 95% CI: 0.07-0.31, P<0.00001) were increased in the 5-fluorouracil group.

Conclusions: Raltitrexed-based chemotherapy regimen leads to an equivalent overall survival and response rates with acceptable toxicities compared to traditional 5-fluorouracil-based regimen in patients with advanced colorectal cancer. Raltitrexed can be a treatment option for these patients when 5-fluorouracil-based regimens are not tolerated or inappropriate.

Keywords: 5-fluorouracil; Advanced colorectal cancer; Chemotherapy; Meta-analysis; Raltitrexed.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Alopecia / chemically induced
  • Anemia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asthenia / chemically induced
  • Chemical and Drug Induced Liver Injury
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Mucositis / chemically induced
  • Nausea / chemically induced
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects*
  • Randomized Controlled Trials as Topic
  • Stomatitis / chemically induced
  • Thiophenes / administration & dosage*
  • Thiophenes / adverse effects*
  • Vomiting / chemically induced

Substances

  • Organoplatinum Compounds
  • Quinazolines
  • Thiophenes
  • Oxaliplatin
  • raltitrexed
  • Leucovorin
  • Fluorouracil