A study for establishment of individualized chemotherapy for colorectal cancer using the area under the concentration curve (AUC) based on the collagen gel droplet embedded culture-drug sensitivity test (CD-DST)

Abstract

13560 Background: The drug sensitivity of tumor cells is one of the key issues to explore for individualized chemotherapy for cancer patients. We 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 duration. We also reported that growth inhibition rate (IR) and area under the concentration curve (AUC) approximated to logarithmic curve in ASCO 2003 (#1283). The aim of this study was to evaluate the individual 50% inhibitory AUC (AUCIR50) and research the usefulness of individual AUCIR50 for establishment of individualized chemotherapy. Methods: Surgical specimen was obtained from resectable 53 CRC patients without any preoperative chemotherapy during 2002 to 2005. CD-DST was performed under nine different conditions: concentration of 5-FU tested: 0.2, 1 and 10μg/ml; duration of exposure: 3, 24 and 120 hours. After converting drug concentration and contact time to AUC and plotting against growth IR, individual correlation between AUC and growth IR was evaluated. The histogram of individual AUCIR50 was also evaluated. Results: The curve between AUC and growth IR approximated to logarithmic curve in all of the patients (R2=0.69–0.96). We could calculate the individual AUCIR50 in all of the patients (AUCIR50= 23.7–98796298.1μg*hr/ml). The histogram of the individual AUCIR50 (AUCIR50<2500μg*hr/ml) indicated CURT(X) pattern (SK=0.0076). Conclusions: We could obtain a position for each patient on the histogram of AUCIR50. We could also indicate the potential for 5-FU sensitivity to each patient. Some patients demonstrating low 5-FU sensitivity could not be recommended for 5-FU based chemotherapy, and non-5-FU chemotherapy should be explored for them. This study demonstrated that the individual AUCIR50 is useful to distinguish the individualized chemotherapy of colorectal cancer patients. Utilization of CD-DST will facilitate establishment of individualized chemotherapy for colorectal cancer. No significant financial relationships to disclose.