ISSN:
1437-7780
Keywords:
Key words Gastric cancer
;
Low-dose FP
;
Pharmacokinetics
;
Apoptosis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract To analyze the clinical efficacy of a protracted infusion of low-dose 5-fluorouracil (5-FU) and cisplatin (CDDP), a phase II study was performed in 36 patients with advanced gastric cancer. The treatment schedule of the low-dose administration of 5-FU and CDDP (FP) was a continuous infusion of 5-FU (250 mg/m2) for 28 consecu-tive days and a drip infusion of CDDP (3.5 mg/m2) for 5 consecutive days, followed by a 2-day interval each week in one cycle. The overall response rate was 47.2%. Of importance, the improvement in quality of life assessed by performance status (PS) and oral intake was 13.9% and 33.3%, respectively. The toxicity in low-dose FP treatment was less than grade 2, including gastrointestinal toxicities and bone marrow suppression, and this was tolerable during the treatment. The median survival time (MST) and 1-year survival rate were 8 months and 36.2%, respectively. In a pharmacokinetic analysis following the protracted infusion of low-dose FP, the plasma concentrations of 5-FU and CDDP were increased to about 120–130 ng/ml and 0.3–0.5 μg/ml on day 21 after the treatment, respectively. The plasma concentrations of 5-FU and CDDP were not significantly different between responders and non-responders. The tumor response to low-dose FP treatment was associated with the induction of apoptotic cell death and with the overexpression of apoptosis-related genes, such as Bax and Bcl-Xs, in cancer cells. These results indicate that the protracted infusion of low-dose FP could be a useful regimen for patients with advanced gastric cancer, in terms of the high response rate and low toxi-city, possibly leading to the prolongation of survival and improvement in the quality of life.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s101560070007
Permalink
