[Pharmacokinetic modulating chemotherapy highly effective for colorectal carcinoma metastases to multiple organs]

Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high serum 5-fluorouracil (5-FU) concentrations through modulation by uracil. The therapeutic efficacy of PMC and the sensitivity of metastatic lesions to 5-FU were evaluated in advanced colorectal cancer patients.

Thirteen patients with colorectal carcinoma metastases to multiple organs were enrolled. PMC was initiated with a combination of 400 mg of uracil-tegafur daily and 24-hour continuous intravenous infusion of 600 mg/m2 of 5-FU once weekly. The 5-FU dose was escalated when the disease progressed. When PR was achieved, serum 5-FU concentrations were monitored in order to evaluate the chemosensitivity of each metastatic lesion to 5-FU.

PR in the target lesion was observed in 7 of 11, 6 of 10, 2 of 2, and 2 of 4 patients with metastatic lesions to the liver, lungs, peritoneum and lymph nodes, respectively. The area under the concentration-time curve (AUC ng x hr/ml) of the 5-FU sufficient to induce PR in pulmonary lesions, 3528 to 9684, was significantly higher than for hepatic lesions, 2413 to 6323 (p = 0.028). The median survival was 13 months.

PMC, having a chronomodulating nature, is highly effective in treating colorectal carcinoma metastases with a superior safety profile. Pulmonary metastases are more resistant to 5-FU than hepatic metastases, as they require a higher 5-FU AUC to respond.