Personalized adjuvant chemotherapy for colorectal cancer based on an individual 50% inhibitory area under the concentration curve using collagen gel droplet embedded culture-drug sensitivity test.

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.

Download Full-text

A study for establishment of individualized chemotherapy for colorectal cancer based on the individual 50% inhibitory area under the concentration curve (AUCIR50) using the collagen gel droplet embedded culture-drug sensitivity test (CD- DST)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14553 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14553-14553

Author(s):

T. Ochiai ◽

K. Nishimura ◽

T. Watanabe ◽

M. Kitajima ◽

N. Konishi ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Drug Sensitivity ◽

Collagen Gel ◽

Concentration Curve ◽

Recurrence Rates ◽

Drug Sensitivity Test ◽

The Individual ◽

Individualized Chemotherapy

14553 Background: The drug sensitivity of tumor cells is one of the key issues to explore in individualized 5-fluorouracil (5-FU) based chemotherapy for colorectal cancer patients. We reported that growth inhibition rate (IR) and area under the concentration curve (AUC) approximated to a logarithmic curve using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) in ASCO 2003 (#1283). We also reported that the individual 50% inhibitory area under the concentration curve (AUC IR50) could be obtained using the individual AUC-IR curve in ASCO 2006 (#13560). The aim of this study was to evaluate the achievement of the individual AUCIR50 in 5-FU based adjuvant chemotherapy for the establishment of individualized chemotherapy. Methods: Surgical specimen was obtained from resectable 33 CRC patients without any preoperative chemotherapy during 2001 to 2005. 5-FU based adjuvant chemotherapy was administered in all patients. CD-DST was performed under 6–9 different conditions. The individual AUCIR50 was obtained from the individual AUC-IR curve. The patients were divided into 2 groups, the achieved group and the non-achieved group. In the achieved group, total administered AUC was more than the individual AUCIR50 and in non-achieved group, the total administered AUC was less than the individual AUCIR50. Recurrence rates were evaluated from the 2 groups. Results: In all patients, the recurrence rates were 6.7% (1/15) in the achieved group and 27.8% (5/18) in the non-achieved group. In the colon cancer patients, the recurrence rates were 8.3% (1/12) in the achieved group and 10.0% (1/10) in the non-achieved group. In the rectal cancer patients, the recurrence rates were 0% (0/3) in the achieved group and 50.0% (4/8) in the non-achieved group. Conclusions: The recurrence rate of the achieved group was lower than that of the non-achieved group. Therefore, this study demonstrated that the achievement of the individual AUCIR50 could be a prerequisite of individualized 5-FU based adjuvant chemotherapy. No significant financial relationships to disclose.

Download Full-text