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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Muneoka
Katsuki
K
Dept. of Surgery, Niitsu Medical Center Hospital, Niigata University Graduate School of Medical and Dental Sciences.
Shirai
Yoshio
Y
Wakai
Toshifumi
T
Yokoyama
Naoyuki
N
Okumura
Shuzo
S
Hatakeyama
Katsuyoshi
K
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000473:pathology*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015918:Infusion Pumps, Implantable; D007261:Infusions, Intra-Arterial; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin; D005472:Fluorouracil