Failure of orally administered dipyridamole to enhance the antineoplastic activity of fluorouracil in combination with leucovorin in patients with advanced colorectal cancer: A prospective randomized trial

C. H. Kohne, W. Hiddemann, J. Schuller, J. Weiss, H. P. Lohrmann, U. Schmitz- Hubner, H. Bodenstein, C. Schober, H. Wilke, J. Grem, H. J. Schmoll

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Purpose: A randomized trial was performed to investigate the ability of the nucleoside transport inhibitor dipyridamole (DP) to enhance the antitumor activity of fluorouracil (5-FU)/leucovorin (folinic acid [FA]). Patients and Methods: One hundred eighty-one untreated patients with advanced colorectal cancer were randomized to receive 5-FU 600 mg/m2 plus FA 300 mg/m2 on days 2 to 4 with or without DP 75 mg orally three times daily on days 1 to 5. Cycles were repeated every 3 weeks. Only patients with documented tumor progression before therapy were eligible. 5-FU pharmacokinetics using high- performance liquid chromatography (HPLC) were assessed in 11 nonrandomized patients receiving paired cycles with or without DP. Results: One hundred seventy-four patients were assessable for toxicity and response. There was no significant difference in toxicity, except DP-related headache in 24% of patients. An objective response rate of 15% (one complete response [CR] and 13 partial responses [PRs]) for 5-FU/FA and 13% (two CRs and nine PRs) for 5- FU/FA/DP was observed. The dose-intensity of 5-FU delivered was significantly higher (1.09- to 1.16-fold) for the DP-containing arm. Pharmacokinetic parameters of 5-FU did not differ significantly, except for a prolonged half- life (t( 1/2 )) induced by DP. The median time to progression (P = .8) and the median survival time (11.6 months for 5-FU/FA v 9.3 months for 5-FU/FA/DP; P = .14, log-rank test) were not different between treatment arms. Conclusion: Orally administered DP did not improve the antineoplastic activity of 5- FU/FA in patients with advanced colorectal cancer when used at this dose and schedule. The observed increase in 5-FU dose-intensity for FU/FA/DP was not clinically relevant.

Original languageEnglish (US)
Pages (from-to)1201-1208
Number of pages8
JournalJournal of Clinical Oncology
Volume13
Issue number5
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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