Phase I trial of sequential raltitrexed followed by bolus 5-fluorouracil in patients with advanced colorectal cancer

Gary K. Schwartz, Joseph Bertino, Nancy Kemeny, Leonard Saltz, David K. Kelsen, William Tong, Mary Welch, Sandra Endres, Isaiah Dimery

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Our objective was to determine the maximum tolerated dose (MTD) of sequential raltitrexed (Tomudex) and 5-fluorouracil (5-FU) by bolus administration every 3 weeks in patients with advanced colorectal cancer (aCRC) and appendiceal adenocarcinoma. This phase I dose-escalation study was carried out in three stages: (1) 5-FU fixed at 900 mg/m2, raltitrexed escalated from 0.5 to 3.0 mg/m2, (2) raltitrexed fixed at 3.0 mg/m2, 5-FU escalated from 900 mg/m2 until dose-limiting toxicity (DLT) and (3) 5-FU fixed at the dose level below DLT, raltitrexed escalated from 3.0 mg/m2 until MTD. Seventy-one patients with measurable disease were enrolled. No DLTs were observed during stage 1 of treatment. At a fixed dose of raltitrexed 3.0 mg/m2, DLT developed when 5-FU was increased to 1350 mg/m2 (stage 2). When 5-FU was fixed at 1200 mg/ m2 and raltitrexed was increased to 6.0 mg/m2 (stage 3), DLT was dose limiting. The recommended doses for further study are 5.5 mg/m2 ralitrexed and 1200 mg/m2 5-FU. Of the 69 patients evaluated for efficacy, one had a complete response (8.0 months) and five had partial responses (5.1-11.6 months). Thirty patients had stable disease for 5 or more cycles of therapy (mean time to progression: 3.6 months). Median survival was 11.7 months. We conclude that raltitrexed can be combined with bolus 5-FU, at raltitrexed doses that are higher than the recommended single-agent dose of 3.0 mg/m2, with manageable toxicity. This combination shows encouraging activity, and survival appears promising in the pre-treated aCRC patient population. Further clinical trials are warranted.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalAnti-Cancer Drugs
Issue number3
StatePublished - Mar 2004
Externally publishedYes


  • 5-flurouracil
  • Colorectal cancer
  • Dose escalation
  • Raltitrexed

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research


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