Impact of primary tumor location as a predictive factor in patients suffering from colorectal cancer treated with cytotoxic anticancer agents based on the collagen gel droplet‑embedded drug sensitivity test

BackgroundPrimary tumor location (PTL) is an important prognostic and predictive factor in the first-line treatment of metastatic colorectal cancer (mCRC). Although regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have been introduced recently, the clinical impact of PTL in these treatments is not well understood.Materials and MethodsWe retrospectively evaluated patients with mCRC who were registered in a multicenter observational study (the REGOTAS study). The main inclusion criteria were Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2, refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, angiogenesis inhibitors, anti-epidermal growth factor receptor therapy (if RAS wild-type), and no prior use of REG and FTD/TPI. The impact of PTL on overall survival (OS) was evaluated using Cox proportional hazard models based on baseline characteristics.ResultsA total of 550 patients (223 patients in the REG group and 327 patients in the FTD/TPI group) were included in this study, with 122 patients with right-sided tumors and 428 patients with left-sided tumors. Although the right-sided patients had significantly shorter OS compared with the left-sided patients by univariate analysis (p = 0.041), a multivariate analysis revealed that PTL was not an independent prognostic factor (hazard ratio, 0.95; p = 0.64). In a subgroup analysis, the OS was comparable between the REG and FTD/TPI groups regardless of PTL (p for interactions = 0.60).ConclusionsIn the present study, PTL is not a prognostic and predictive factor in patients with mCRC under later-line REG or FTD/TPI therapy.

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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)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13560 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13560-13560

Author(s):

T. Ochiai ◽

K. Nishimura ◽

H. Noguchi ◽

M. Kitajima ◽

A. Tsukada ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Drug Sensitivity ◽

Collagen Gel ◽

Sensitivity Test ◽

Concentration Curve ◽

Drug Sensitivity Test ◽

Logarithmic Curve ◽

The Individual ◽

Individualized Chemotherapy

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.

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