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Titolo:
Schedule specific biochemical modulation of 5-fluorouracil in advanced colorectal cancer: A randomized study
Autore:
Sobrero, A; Zaniboni, A; Frassineti, GL; Aschele, C; Guglielmi, A; Giuliani, R; Ravaioli, A; Lanfranco, C; Caroti, C; Arnoldi, E; Barni, S; Gallo, L; Pessi, MA; Turci, D; Cortesi, E; Grossi, F; Frontini, L; Piazza, E; Bruzzi, P; Labianca, R;
Indirizzi:
Univ Udine, Dept Med Oncol, I-33100 Udine, Italy Univ Udine Udine Italy I-33100 ine, Dept Med Oncol, I-33100 Udine, Italy Casa Cura Poliambulanza, Brescia, Italy Casa Cura Poliambulanza Brescia Italy ura Poliambulanza, Brescia, Italy Osped Morgagni Pierantoni, Forli, Italy Osped Morgagni Pierantoni Forli Italy Morgagni Pierantoni, Forli, Italy Osped Galliera, Genoa, Italy Osped Galliera Genoa ItalyOsped Galliera, Genoa, Italy Univ La Sapienza, Policlin Umberto I, Rome, Italy Univ La Sapienza Rome Italy a Sapienza, Policlin Umberto I, Rome, Italy Osped Infermi, Rimini, Italy Osped Infermi Rimini ItalyOsped Infermi, Rimini, Italy Osped Civile Asti, Asti, Italy Osped Civile Asti Asti ItalyOsped Civile Asti, Asti, Italy Osped Bolognini, Seriate, Italy Osped Bolognini Seriate ItalyOsped Bolognini, Seriate, Italy Osped Treviglio, Treviglio, Italy Osped Treviglio Treviglio ItalyOsped Treviglio, Treviglio, Italy Osped Riuniti Bergamo, I-24100 Bergamo, Italy Osped Riuniti Bergamo Bergamo Italy I-24100 gamo, I-24100 Bergamo, Italy Osped S Maria Croci, Ravenna, Italy Osped S Maria Croci Ravenna ItalyOsped S Maria Croci, Ravenna, Italy Osped San Paolo, Milan, Italy Osped San Paolo Milan ItalyOsped San Paolo, Milan, Italy Osped Sacco, Milan, Italy Osped Sacco Milan ItalyOsped Sacco, Milan, Italy Ist Nazl Ric Canc, I-16132 Genoa, Italy Ist Nazl Ric Canc Genoa Italy I-16132 azl Ric Canc, I-16132 Genoa, Italy
Titolo Testata:
ANNALS OF ONCOLOGY
fascicolo: 11, volume: 11, anno: 2000,
pagine: 1413 - 1420
SICI:
0923-7534(200011)11:11<1413:SSBMO5>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH-DOSE LEUCOVORIN; CONTINUOUS-INFUSION; PHASE-II; FLUOROURACIL FAILURE; MULTICENTER TRIAL; FOLINIC ACID; BOLUS; OXALIPLATIN; CARCINOMA; CHEMOTHERAPY;
Keywords:
advanced colorectal cancer; biochemical modulation; 5-fluorouracil; schedule of administration;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Sobrero, A Univ Udine, Dept Med Oncol, Piazza S Maria 1, I-33100 Udine, Italy Univ Udine Piazza S Maria 1 Udine Italy I-33100 0 Udine, Italy
Citazione:
A. Sobrero et al., "Schedule specific biochemical modulation of 5-fluorouracil in advanced colorectal cancer: A randomized study", ANN ONCOL, 11(11), 2000, pp. 1413-1420

Abstract

Background: We have recently suggested that bolus 5-fluorouracil (5-FU) may work via a RNA directed mechanism while continuous infusion 5-FU may killcells via a thymidylate synthase related pathway. It may thus be possible to selectively modulate each schedule biochemically. We have compared an alternating regimen of bolus and continuous infusion 5-FU, selectively modulated for the schedule of administration, with modulated bolus 5-FU in advanced colorectal cancer patients. Patients and methods: Two hundred fourteen patients from nineteen Italian centers were randomized to the control arm consisting of biweekly cycles ofMTX, 200 mg/m(2) on day 1, followed by bolus 5-FU 600 mg/m(2) on day 2 and6-S-leucovorin rescue, or to the experimental arm consisting of two biweekly cycles of the same regimen as in the control arm alternated to three weeks of continuous infusion 5-FU (200 mg/m(2) day) + weekly bolus 6-S-leucovorin, 20 mg/m(2). Results: Nine CR and twenty-seven PR were obtained on one hundred eleven evaluable patients treated in experimental arm (RR = 32%, 95% confidence interval (95% CI): 24%-42%), while two CR and eleven PR were observed among one hunderd three evaluable patients in control arm (RR = 13%, 95% CI: 7%-21%). WHO grade 3-4 toxicity occurred in 13% of cycles of experimental arm andin 8% of cycles in control arm. The PFS was significantly longer in experimental arm (6.2 vs. 4.3 months, odds ratio 0.66, P = 0.003), while the overall survival was similar in both arms (14.8 months in experimental arm vs. 14.1 months in control arm); quality of life was similar as well. Eighty percent of patients receiving second-line chemotherapy in control arm were treated with continuous infusion 5-FU. Conclusions: Alternating, schedule-specific biochemical modulation of FU is more active than MTX --> 5-FU as first-line treatment of advanced colorectal cancer. However, the overall survival was similar suggesting that alternating bolus and infusional 5-FU upfront may be as effective as giving themin sequence as first- and second-line treatment.

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Documento generato il 06/04/20 alle ore 05:09:37