Abstract.We have previously reported the 5-fluorouracil (5-FU) sensitivity of cancer cells from colorectal cancer (CRC) patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Moreover, the area under the concentration curve (AUC) and growth inhibition rate (IR) were combined, resulting in the AUC-IR curve, which was approximated to the logarithmic curve. In the present study, we used the AUC-IR curve to calculate the individualized AUC IR50 , the AUC value that imparts 50% growth inhibition. Individual AUC IR50 was calculated in CRC patients, and its distribution was evaluated. The cumulative distribution of individual AUC IR50 was regressed over two lines (logarithmic scale). Among the 45 resectable CRC patients, those who achieved more than the individual AUC IR50 during post-operative 5-FUbased chemotherapy demonstrated a trend towards better disease-free survival compared to those who did not achieve AUC IR50 . Of the Dukes' D patients (n=10), those who achieved more than twice the individual AUC IR50 during post-operative 5-FU-based chemotherapy demonstrated significantly better survival rates (p=0.05) than those who did not. In this study, the distribution of the individual AUC IR50 suggested that approximately 6% of patients demonstrated very low 5-FU sensitivity. Therefore, the individual AUC IR50 was useful in classifying good, intermediate and poor 5-FU response. Achievement of the individual AUC IR50 may be a prerequisite for individualized 5-FU-based adjuvant chemotherapy. As well, the early achievement of twice the individual AUC IR50 may indicate an improved prognosis in Dukes' D patients. The individual AUC IR50 using CD-DST is useful in determining the individualized chemotherapy of CRC patients, thus CD-DST has the potential to facilitate the establishment of individualized chemotherapy for CRC.
IntroductionIndividualized chemotherapy is a therapeutic strategy based on the features of a respective tumor, and has been proposed to improve patient clinical outcome while maintaining quality of life. In the field of gastrointestinal cancer, 5-fluorouracil (5-FU) is the drug most often used to assess antitumor effect. The drug sensitivity of tumor cells is one of the key factors that must be assessed in individualized chemotherapy for cancer patients. We have reported the 5-FU sensitivity of cancer cells from colorectal cancer (CRC) patients using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) under multiple drug concentrations and contact durations. Moreover, the area under the concentration curve (AUC) and growth inhibition rate (IR) were combined, resulting in the AUC-IR curve, which was approximated to the logarithmic curve (1). We have also reported that the growth inhibition rate, calculated from the AUC-IR curve, and the actual growth inhibition rate, at an AUC of 48 μg x h/ml, are identical. Based on these results, we proposed that the in vitro antitumor effect of 5-FU depends o...