KOHNE, CH and HIDDEMANN, W and SCHULLER, J and WEISS, J and LOHRMANN, HP and SCHMITZHUBNER, U and BODENSTEIN, H and SCHOBER, C and WILKE, H and GREM, J and SCHMOLL, HJ (1995) 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. JOURNAL OF CLINICAL ONCOLOGY, 13 (5). pp. 1201-1208. ISSN 0732-183X, 1527-7755
Full text not available from this repository.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/m(2) plus FA 300 mg/m(2) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHASE-I TRIAL; FOLINIC ACID; BIOCHEMICAL MODULATION; CONTINUOUS INFUSION; CYTO-TOXICITY; 5-FLUOROURACIL; CARCINOMA; CELLS; AUGMENTATION; CHEMOTHERAPY; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/52562 |
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