Leucovorin + 5-fluorouracil plus dipyridamole in leucovorin + 5-fluorouracil-pretreated patients with advanced colorectal cancer: a pilot study of three different dipyridamole regimens.

摘要: Dipyridamole, an inhibitor of nucleoside transport, increases the activity 5-fluorouracil in a dose-dependent manner. The purpose present study was to determine whether dipyridamole with and leucovorin gave improved therapeutic outcome. Sixty patients entered pilot had previously received (450 mg/m2) (100 mg/m2), every week, relapsed during this treatment, which ended at least 6 weeks prior entry. Dipyridamole administered three different dosing schedules (DS) methods administration groups patients. DS I: dipyridamole, 30 mg/m2 normal saline solution, 90 min iv infusion, followed by leucovorin, 100 push, 5-fluorouracil, 450 60 tablets (75 mg) 12 hrs, continuously time chemotherapy. II: 50 rest same as I. III: without oral (50 manner I II. Treatment continued until tumor progression or unacceptable toxicity. All (n = 60) were assessable for response No complete observed. patient responded, whereas 2 II 3 III partial (P <0.1). Stable disease found 1), 8) 9) <0.01). More progressed 19) than 10) <0.0007). median duration 11 (range, 8-16). Time 17 I, 15 10-19) II, 14 11-21) 0.43). Median survival did not differ significantly between (29 weeks; range, 14-48), II(31.5 17-63) (36 16-58) 0.2). Neutropenia most severe (grade 2, P<0.01) 1, P<0.05) nausea/vomiting 0, P < 0.0005, grade <0.0002, <0.02) 3, P<0.0009). Diarrhea <0.005). Mucositis increased <0.008), anorexia <0.032) fatigue <0.003). other two experienced headache <0.044). According achieved (15% 45% stable disease) toxicity well tolerated mainly (except nausea vomiting <0.009), it can be stated that is appropriate dose simplest schedule (administration therapy only). In conclusion, appears might still have role enhancing clinical drugs involved inhibition thymidylate synthetase biochemical pathway its combination these agents (5-fluorouracil + leucovorin) frontline treatment should therefore explored future phase studies.