PURPOSE: 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.
PURPOSE: 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: C H Köhne; P Schöffski; H Wilke; C Käufer; R Andreesen; U Ohl; U Klaasen; M Westerhausen; W Hiddemann; G Schott; A Harstick; J Bade; A Horster; U Schubert; H Hecker; B Dörken; H J Schmoll Journal: J Clin Oncol Date: 1998-02 Impact factor: 44.544
Authors: S Giacchetti; B Perpoint; R Zidani; N Le Bail; R Faggiuolo; C Focan; P Chollet; J F Llory; Y Letourneau; B Coudert; F Bertheaut-Cvitkovic; D Larregain-Fournier; A Le Rol; S Walter; R Adam; J L Misset; F Lévi Journal: J Clin Oncol Date: 2000-01 Impact factor: 44.544
Authors: C H Köhne; D Cunningham; F Di Costanzo; B Glimelius; G Blijham; E Aranda; W Scheithauer; P Rougier; M Palmer; J Wils; B Baron; F Pignatti; P Schöffski; S Micheel; H Hecker Journal: Ann Oncol Date: 2002-02 Impact factor: 32.976
Authors: A de Gramont; J F Bosset; C Milan; P Rougier; O Bouché; P L Etienne; F Morvan; C Louvet; T Guillot; E François; L Bedenne Journal: J Clin Oncol Date: 1997-02 Impact factor: 44.544
Authors: P Piedbois; P Rougier; M Buyse; J Pignon; L Ryan; R Hansen; B Zee; B Weinerman; J Pater; C Leichman; J Macdonald; J Benedetti; J Lokich; J Fryer; G Brufman; R Isacson; A Laplanche; E Levy Journal: J Clin Oncol Date: 1998-01 Impact factor: 44.544
Authors: T S Maughan; R D James; D J Kerr; J A Ledermann; C McArdle; M T Seymour; D Cohen; P Hopwood; C Johnston; R J Stephens Journal: Lancet Date: 2002-05-04 Impact factor: 79.321
Authors: H Curé; V Chevalier; A Adenis; N Tubiana-Mathieu; G Niezgodzki; F Kwiatkowski; D Pezet; B Perpoint; B Coudert; C Focan; F Lévi; J Chipponi; P Chollet Journal: J Clin Oncol Date: 2002-03-01 Impact factor: 44.544
Authors: P Rougier; E Van Cutsem; E Bajetta; N Niederle; K Possinger; R Labianca; M Navarro; R Morant; H Bleiberg; J Wils; L Awad; P Herait; C Jacques Journal: Lancet Date: 1998-10-31 Impact factor: 79.321