title: Phase I study of high dose 5-fluorouracil and high dose Leucovorin with low dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies.
abstract: Twenty-eight patients with refractory advanced malignancies were treated with a 24 hr infusion of 5-fluorouracil (5-FU), Leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable for the assessment of toxicity and anti-tumor activity. PALA was administered as intravenous bolus over 15 min at a fixed dose, 250 mg/m2 24 hr before the start of 5-FU and LV infusions. 5-FU was initially administered at 750 mg/m2 and was incrementally increased to 2600 mg/m2. LV was administered in a fixed dose of 500 mg/m2 concurrently with 5-FU over a 24-hr period. The course was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among dose-limiting toxic effects. Other toxicities observed were hand-foot syndrome, hair loss of scalp/eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. Maximum tolerated dose (MTD) of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated at 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose de-escalation, a majority of whom contained 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients had been previously treated. Eight patients achieved a partial response, all of whom were previously treated, except three patients. A complete response was observed in a patient with pancreatic carcinoma, previously untreated. Overall response rate for the patients who were treated at the 5-FU dose of 2100 mg/m2 or 2600 mg/m2 is 9 of 18 patients (50%).
authors.affiliation: Department of Oncology, University of Miami School of Medicine, Jackson Memorial Hospital, FL.
authors.forename: B
authors.initials: B
authors.lastname: Ardalan
authors.forename: K
authors.initials: K
authors.lastname: Stridhar
authors.forename: R
authors.initials: R
authors.lastname: Reddy
authors.forename: P
authors.initials: P
authors.lastname: Benedetto
authors.forename: S
authors.initials: S
authors.lastname: Richman
authors.forename: S
authors.initials: S
authors.lastname: Waldman
authors.forename: L
authors.initials: L
authors.lastname: Morrell
authors.forename: L
authors.initials: L
authors.lastname: Feun
authors.forename: N
authors.initials: N
authors.lastname: Savaraj
authors.forename: A
authors.initials: A
authors.lastname: Livingstone
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001224:Aspartic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D002955:Leucovorin; D005472:Fluorouracil