A Phase I Trial of HDFL48 in Recurrent or Metastatic Colorectal Cancers

Colorectal cancer is one of the major in Taiwan.It caused 3128 deaths in 1999, and represented the No.3 cancer killer in both male and female population of Taiwan.

Recently, evidence has accumulated that weekly, 24-hour infusion of high-dose 5-FU may improve the response rate and survival time compared with 5-FU bolus regiment. In a randomized multicenter trial of metastatic colorectal cancer, Kohne et al reported an overall response rate of 44%and a median survival time of 16 months using a weekly-times-six schedule of infusional 5-FU (2600mg/m2 24-hours infusion). In another randomized study for advanced colorectal cancer, de Gramont et al reported a significantly better outcome in patients treated by a similar schedule which combined "bolus plus infusional" 5-FU compared to "bolus" 5-FU. These results suggest that 24-or 48-hour infusion of high-dose 5-FU is more effective than the conventional bolus schedules.

Inclusion criteria

• Pathologically confirmed recurrent or metastatic colorectal adenocarcinoma
• Patients are indicated for 5-FU (1st-line after recurrence/metastasis), OR have failed 5-FU ,treatment with other schedules
• At least one bi-dimensionally measurable lesion(s)
• Previous C/T, R/T >= 4 weeks
• KPS > 50%
• Age >= 18 years
• Fasting TG > 70 mg/dL (within 7 days)
• WBC >= 3,000/uL or ANC >= 1,500/uL
• Plt >= 75,000/uL
• Cre<= 1.5 mg/dL
• Proteinuria < 1+
• Normal T-bil
• AST/ ALT <= 3.5-fold of ULN

Exclusion criteria

• Concomitant anticancer therapy or radiotherapy
• CNS metastasis
• Pregnant women
• Patients who have second malignancy
• Symptomatic heart disease (significant arrhythmia, CHF or MI within 3 months of entry)
• Active infection exists
• Extensive liver disease or liver cirrhosis
• Patients who refuse Port-A catheter implantation