Treatment Of Advanced Gastric Cancer With The Regimen Of Continuous Venous Infusion Of 5-Fluorouracil And Low-dose Cisplatin

Objective: Gastric cancer is a fatal disease with a poor patient prognosis and is the second leading cause of cancer death worldwide. Surgical resection is one of the primary treatments. Adjuvant chemotherapy in Western population showed the efficacy with remained questions of its application to D2 resection group. Gastric cancer is diagnosed at late stages in most countries, most patients with gastric cancer present with metastasis or advanced disease at the time of diagnosis. Almost 60-80% gastric cancer patients lost the operation opportunity to cure the disease. Chemotherapy is the primary treatment. Chemotherapy could improve quality of life and prolong the survival of patients with advanced gastric cancer .A standard chemotherapy regiment for advanced gastric cancer has not yet been established, although there are numerous chemotherapy regimen available. Presently, only a few anticancer drugs have been approves for use. Clinical investigation of new drugs such as Paclitaxel, docetaxel ,CPT-11, S-1 and capecitabine have been presented or currently ongoing. The availability of new anti-cancer drugs in advanced gastric cancer has started to change the standard of care. Previous reports have indicated that biweekly Oxaliplatin combined with 5-flurouracil(5-FU) and leucovorin(CF) is very effective and less toxic effects, especially suitable for advanced colorectal, and now it has been use to treat advanced gastric cancer. Combination chemotherapy of continuous venous infusion of 5-FU and low-dose cisplatin(DDP) has been approved for use against advanced gastric cancer and was well tolerated for the treatment of advanced gastric cancer. The aim of this study was to assess the recent efficacy and tolerability of two drug combinations of continuous venous infusion of 5-FU and low-dose DDP(FP)and Oxaliplatin in combination with CF, 5-FU(FOLFOX4)in advanced gastric cancer. Methods: The eligibility criteria were as follows: advanced gastric cancer .with stage IV(T₄ N3, M₁) disease ,with histological confirmation of adenocarcinoma or adenosquamous carcinoma et al, at least one measurable lesion, a Karnofsky performance status of 60 to 100%,a patients age of 23 to 74 years, median age 51 years, males were 38 and female were 28 ,adequate organ functions, no chemotherapy in recent one month, a life expectancy of more than three months. From March 2002 to March 2005, 66 patients with advanced gastric cancer were enrolled for study, in a randomized manner, 66 patients with advanced gastric cancer were divided into two groups, details history of two group including age, sex, histology TNM staging and other investigational records were documented and analyzed: FP group treated with 5-FU 300 mg/m²/d continuous infusion for 24 hours and DDP 1-hour drip with 4 mg/m²/d on day 1-5 every week , which were used for 3 weeks, the treatment schedule was recycled every 42 days. FOLFOX4 group were given intravenously oxaliplatin(L-OHP)3-hour drip with 85 mg/m² on day 1 , CF 2-hour drip simulateneously with 200 mg/m² on day 1, then 5-FU 400 mg/m² , in bolus, 600 mg/m² continuous infusion for 22 hours, CF and . 5-FU were repeated on day 2. the treatment schedule was recycled every 14 days. An extramural review board assessed the tumor responses by applying the World Health Organization. Toxicity was graded according to the World Health Organization common toxicity criteria standard. Results: There were 2 patients not eligible for study and 31 patients of FP group might be evaluated for clinical response, .complete response was observed in 1 patient(3.22%),partial response was observed in 10 patient(32.26%),no change was observed in 7 patient(22.58%),progressive disease was observed in 13 patient(41.94%).The total response rate in FP group was 35.48%. The median time to disease progression was 3.2 months,There were 2 patients not eligible for study and 30 patients of FOLFOX4 group might be evaluated for clinical response .complete response was observed in 1 patient(3.33%), partial response was observed in 11 patient(36.67%),no change was observed in 10 patient(33.33%), progressive disease was observed in 8 patient(26.67%).The total response rate in FOLFOX4 group was 40.00%. The median time to disease progression was 6.8 months,The major gradeIII/IV toxicities in FP group were vomiting(16.12%), diarrhea (9.67%), the incidenceds of other grade III/IV toxicities were less than 5%. The major grade III/IV toxicities in FOLFOX4 group were leukonic(33.33%), vomiting(16.12%), numbness(16.12%), anemia( 13.33%), the incidenceds of other grade III/IV toxicities were less than 5%. Conclusion: FP regimen and FOLFOX4 regimen have similar recent effect and were both well tolerated for the treatment of advanced gastric cancer.