title: High-dose chronomodulated infusion of 5-fluorouracil (5-FU) and folinic acid (FA) (FF5-16) in advanced colorectal cancer patients.
abstract: OBJECTIVE
  The best way to deliver infusional 5-fluorouracil (5-FU) and folinic acid (FA) has yet to be determined. The aim of this prospective phase II trial was to verify the tolerability, activity and efficacy of chronomodulated 5-FU-FA (FF(5-16)) every 3 weeks in 48 untreated patients (group A), and 28 pretreated and four non-measurable, advanced colorectal cancer (ACC) patients (group B).
  
  
  METHODS
  The sinusoidal delivery of both drugs started at 10.00 p.m. and ended at 10.00 a.m., with peak flow at 4.00 a.m. for 5 consecutive days. The initial 5-FU dose was 900 mg/m(2)/day with intra-patient dose increase at 1,000 and 1,100 mg/m(2)/day, at the second and third course, respectively; FA was injected at a fixed dose of 150 mg/m(2)/day (Garufi et al.1997).
  
  
  RESULTS
  Neither death from toxicity nor hematological toxicities were encountered. Maximal toxicity consisted of Grade 3 oral mucositis in 41% of patients, in only 8% of 535 courses. It was possible to achieve objective responses in 31% of untreated patients, with a progression free survival (PFS) of 7 months, median survival of 14 months and a 2-year survival rate of 28%. Similar results for PFS and survival were obtained in pretreated patients as well. Univariate analysis and multivariate analysis showed that response was related to the occurrence of mucositis and diarrhea ( p=0.03 and p=0.0007) and to performance status (PS) ( p=0.01). Quality of life, measured with the EORTC QLQ-C30+3 questionnaire, was unaffected by treatment and was better in patients with good PS and responsiveness.
  
  
  CONCLUSIONS
  In this chronomodulated FF(5-16) phase II study, the probability of obtaining a relevant tumor reduction was significantly correlated with a patient variable such as PS, and toxicity variables such as mucositis and diarrhea. This observation and the validation of predictive factors for QoL deserve further investigation in ACC patients.
authors.affiliation: SC Oncologia Medica C, Istituto Regina Elena, Istituti Fisioterapici Ospitalieri, Via E. Chianesi, 53, 00144 Rome, Italy. garufi@ifo.it
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
authors.forename: Carlo
authors.initials: C
authors.lastname: Garufi
authors.forename: Albina Rita
authors.initials: AR
authors.lastname: Zappalà
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanni
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pugliese
authors.forename: Giancarlo Antonini
authors.initials: GA
authors.lastname: Cappellini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Aschelter
authors.forename: Maria
authors.initials: M
authors.lastname: Perrone
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil