title: Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer.
abstract: To improve the efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in metastatic esophageal cancer, we designed a new therapeutic schedule, the HLFP regimen. 42 patients with metastatic oesophageal adenocarcinoma (n=10) or squamous cell carcinoma (n=32) were prospectively enrolled in the study. All had bidimensionally measurable disease. The HLFP regimen consisted of twice-monthly oral administration of hydroxyurea 1 g/m(2) on days 0, 1 and 2; a 2-h infusion of leucovorin 200 mg/m(2) and a bolus of 5-FU 400 mg/m(2) followed by a 22-h infusion of 5-FU 600 mg/m(2) on days 1 and 2; and, every two cycles, 80 mg/m(2) cisplatin on day 3. Relief of dysphagia and other symptoms were monitored, together with body weight changes. Major objective responses were observed in 24 patients (57%, 95% Confidence Interval (CI): 42-72%), including four complete responses (10%). The median progression-free survival and overall survival times were 8 and 12.7 months, respectively. Weight gain was observed in 48% of patients, and dysphagia improved in 76%. Grade 3-4 toxicity occurred in 40% of patients, with grade 4 neutropenia in 12% and grade 3 thrombocytopenia, vomiting and diarrhoea in 7-9% of patients. There were no treatment-related deaths. These results suggest that the HLFP regimen is an active and well-tolerated chemotherapy for metastatic oesophageal carcinoma.
authors.affiliation: Médecine Interne-Oncologie, Hôpital St-Antoine, 184 rue du faubourg Saint-Antoine, 75571 Paris cedex 12, France. jtaieb@club-internet.fr
authors.forename: J
authors.initials: J
authors.lastname: Taïeb
authors.forename: P
authors.initials: P
authors.lastname: Artru
authors.forename: B
authors.initials: B
authors.lastname: Baujat
authors.forename: M
authors.initials: M
authors.lastname: Mabro
authors.forename: E
authors.initials: E
authors.lastname: Carola
authors.forename: F
authors.initials: F
authors.lastname: Maindrault
authors.forename: C
authors.initials: C
authors.lastname: Tournigand
authors.forename: M
authors.initials: M
authors.lastname: Krulik
authors.forename: C
authors.initials: C
authors.lastname: Louvet
authors.forename: A
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D003680:Deglutition Disorders / Q000188:drug therapy; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002945:Cisplatin; D005472:Fluorouracil