Study to predict optimal duration of chemotherapy with fluoropyrimidine by multi-point collagen gel droplet embedded drug sensitivity test.

BACKGROUND/AIMS: In colorectal cancer (CRC), 5-fluorouracil (5-FU) has been a basic chemotherapeutic agent. Antitumor effects of 5-FU and its derivatives are likely due to inter-individual difference in the drug sensitivity.

METHODOLOGY

We evaluated the 5-FU sensitivity of cancer cells from CRC patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentration and contact durations. The area under the concentration curve (AUC) and growth inhibition curve (IR) were combined in the AUC-IR curve. Using the AUC-IR curve, the individual AUC(IR50) was calculated. Furthermore, using the AUC values of 5-FU during 24 hours with chemotherapy with UFT and S-1, the durations to achieve the AUC(IR50) were calculated in chemotherapy with UFT or S-1 for individual patient.

RESULTS

The value of individual AUC(IR50) ranged widely from less than 100 microg hr/ml to more than 1000 microg hr/ml. Approximately 13% of patients demonstrated a relatively low 5-FU sensitivity. Durations of chemotherapy to achieve the AUC(IR50) differed widely depending on the AUC(IR50) of individual patient. Relapse free survival was significantly better in the patients who have achieved individual AUC(IR50) than those who have not achieved the AUC(IR50).

CONCLUSIONS

The present results suggest that the antitumor effects of 5-FU and its derivatives differ widely depending on inter-individual difference of sensitivity, and that individual AUC(IR50) may be useful to predict the optimal duration of chemotherapy.