title: A phase I, II 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-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.
authors.affiliation: University of Miami Sylvester Comprehensive Cancer Center, Florida.
authors.forename: B
authors.initials: B
authors.lastname: Ardalan
authors.forename: K S
authors.initials: KS
authors.lastname: Sridhar
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: M
authors.initials: M
authors.lastname: Fodor
authors.forename: A
authors.initials: A
authors.lastname: Livingstone
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D001943:Breast Neoplasms / Q000188:drug therapy; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D002955:Leucovorin; D005472:Fluorouracil