Phase I study of eniluracil, oral 5-fluororacil and gemcitabine in patients with advanced malignancy

• Published in: Investigational new drugs Vol. 20; no. 4; pp. 377 - 382
• Main Authors: MORGAN-MEADOWS, Sherry, THOMAS, James P, ARZOOMANIAN, Rhoda Z, WILDING, George, MULKERIN, Daniel, BERLIN, Jordan D, BAILEY, Howard, BINGER, Kim, VOLKMAN, Jennifer, ALBERTI, Dona, FEIERABEND, Chris, MARROCHA, Rebecca
• Format: Journal Article
• Language: English
• Published: Dordrecht Kluwer 01.11.2002; Springer Nature B.V
• Subjects: Administration, Oral; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bioavailability; Biological and medical sciences; Cancer therapies; Chemotherapy; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Diarrhea; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Humans; Lymphoma; Lymphoma - drug therapy; Male; Medical sciences; Middle Aged; Nausea; Neoplasms - drug therapy; Neutropenia; Patients; Patients - statistics & numerical data; Pharmacology. Drug treatments; Thrombocytopenia; Toxicity; Uracil - administration & dosage; Uracil - adverse effects; Uracil - analogs & derivatives; Vomiting; Antineoplastic agent; Human; Solid tumor; Drug combination; Intravenous administration; Eniluracil; Gemcitabine; Toxicity; Fluoropyrimidine derivatives; Oral administration; Malignant hemopathy; Malignant tumor; Increasing dose; Chemotherapy; Treatment; Lymphoproliferative syndrome; Phase I trial; Malignant lymphoma; Pyrimidine derivatives; Advanced stage; Drug interaction; Fluorine Organic compounds; Pyrimidine nucleoside; Fluorouracil
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1023/A:1020673928704

The objectives of this trial were to assess the maximal tolerated dose and toxicity of the combination of oral eniluracil and 5-fluorouracil and intravenous gemcitabine. Patients with histologically confirmed, incurable malignancy (solid tumor or lymphoma) refractory to standard therapy or for which no standard therapy exists were enrolled. The treatment plan consisted of weekly gemcitabine for three weeks with twice daily dosing of 5-FU and eniluracil for 21 days beginning on day one of gemcitabine. Cycles repeated on an every four week schedule. The initial cohort received gemcitabine 800 mg/m2, oral 5-FU 0.6 mg/m2 and eniluracil 6.0 mg/m2. Twenty-six patients were enrolled. Eight patients received less than 2 cycles of therapy. Hematologic and gastrointestinal toxicity predominated, with 48% of courses resulted in grade one or two neutropenia. Hematologic toxicity was dose limiting. One treatment related death occurred. The combination of eniluracil, 5-fluorouracil and gemcitabine offers an oral alternative for 5-FU administration. The recommended phase II dose is gemcitabine 1000 mg/m2, 5FU 1.2 mg/m2 and eniluracil 12 mg/m2.