Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A phase II study of the modulation of 5-fluorouracil and folinic acid withhigh-dose infusional hydroxyurea in metastatic colorectal carcinoma
Autore:
OByrne, KJ; Philip, PA; Propper, DJ; Braybrooke, JP; Saunders, MP; Bates, NP; Taylor, MA; Madigan, D; Ganesan, TS; Talbot, DC; Harris, AL;
Indirizzi:
Churchill Hosp, Imperial Canc Res Fund, Med Oncol Unit, Oxford OX3 7LJ, England Churchill Hosp Oxford England OX3 7LJ ncol Unit, Oxford OX3 7LJ, England Churchill Hosp, Dept Radiol, Oxford OX3 7LJ, England Churchill Hosp Oxford England OX3 7LJ pt Radiol, Oxford OX3 7LJ, England
Titolo Testata:
ANNALS OF ONCOLOGY
fascicolo: 8, volume: 10, anno: 1999,
pagine: 981 - 983
SICI:
0923-7534(199908)10:8<981:APISOT>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
BIOCHEMICAL MODULATION; CANCER; CELLS;
Keywords:
chemotherapy; colorectal cancer; 5-fluorouracil; folinic acid; hydroxyurea; modulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
15
Recensione:
Indirizzi per estratti:
Indirizzo: Harris, AL Churchill Hosp, Imperial Canc Res Fund, Med Oncol Unit, Oxford OX3 7LJ, England Churchill Hosp Oxford England OX3 7LJ Oxford OX3 7LJ, England
Citazione:
K.J. O'Byrne et al., "A phase II study of the modulation of 5-fluorouracil and folinic acid withhigh-dose infusional hydroxyurea in metastatic colorectal carcinoma", ANN ONCOL, 10(8), 1999, pp. 981-983

Abstract

Background: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) byreducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), one of the principal active metabolites of 5-FU, thescheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of 1 mM for six or more hours, significantly enhances the efficacy of 5-FU. Patients and methods: 5-FU/FA was given as follows: days 1 and 2 - FA 250 mg/m(2) (max. 350 mg) over two hours followed by 5-FU 400 mg/m(2) by intravenous bolus (ivb) over 15 minutes and subsequently 5-FU 400 mg/m(2) infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g ivb over 15 minutes followed by 12 g ivi over 12 hours. Results: Thirty patients were entered into the study. Median survival was nine months (range 1-51+ months). There were eight partial responses (28%, 95% CI: 13%-47%). The median duration of response was 6.5 (range 4-9 months). Grade 3-4 toxicities included neutropenia (grade 3 in eight patients andgrade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment wascomplicated by pulmonary embolism in one patient and deep venous thrombosis in another. Conclusion: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 00:20:28