Identification of the optimal cetuximab concentration that is effective against oral squamous cell carcinoma in collagen gel droplet embedded culture drug sensitivity testing

Abstract

Anticancer drug sensitivity testing using the collagen gel droplet embedded culture drug sensitivity test (CD-DST) on oral squamous cell carcinoma (OSCC) samples beginning from 2010 has been conducted. The present study investigated the effect of adding cetuximab (Erbitux ® ), a molecularly targeted drug, on anticancer drug activity against clinical OSCC specimens. A total of 25 specimens were obtained from 25 patients with OSCC between October 2013 and December 2017. The present study conducted anticancer drug sensitivity testing for cisplatin (CDDP), 5-fluorouracil (5-FU), cetuximab, three-drug combination, single agent and multi drug combinations, and cetuximab addition to the aforementioned regimens using CD-DST. In addition, the optimum concentration of each drug was evaluated. The overall evaluation success rate of the CD-DST method for OSCC specimens was 84.0% (21 of 25 cases); sensitivity to anticancer drugs and cetuximab could be evaluated. The in vitro efficacy rate of a cetuximab single agent and CDDP + 5-FU (PF) at a cut-off value of 50% was similar to the known clinical response rate. However, at a cut-off value of 50%, the in vitro efficacy of PF + cetuximab was calculated to be 40%, which was higher than the clinical response rate. The CD-DST method could be used to evaluate cetuximab, a molecularly targeted drug. Furthermore, its additive effect on conventional chemotherapy could be evaluated.The CD-DST method is suitable for evaluating and selecting chemotherapy regimens, including molecularly targeted drugs. Future studies are required to generate and evaluate relevant clinical data. Identification of the optimal cetuximab concentration that is effective against oral squamous cell carcinoma in collagen gel droplet embedded culture drug sensitivity testingAbbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CG, collagen gel-coated; EGFR, epidermal growth factor receptor; OSCC, oral squamous cell carcinoma; SCCHN, squamous cell carcinoma of the head and neck Key words: anticancer drug sensitivity test, oral squamous cell carcinoma, collagen gel droplet embedded culture drug sensitivity test, cetuximab, anticancer drugs

Optimal Contact Concentration of Paclitaxel in the Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test for Human Oral Squamous Cell Carcinoma and Evaluation of Combination with Cetuximab

“…Similarly, as previously reported, sensitivity tests using cisplatin, fluorouracil, or docetaxel for OSCC showed a success rate of 81.8% in primary cultures, with a clinical predictive value of 92.8% [14]. In addition, anticancer drug susceptibility tests, including those of cetuximab-associated samples from patients with OSCC, were performed with success rates of 83.3% for primary tumors, 100% for metastatic lymph nodes, and 84.0% overall [15]. Therefore, the CD-DST can be used to determine the susceptibility of OSCC to various types of anticancer drugs combined with cMab.…”

“…Ryuki et al [21] reported that the results of contact with cisplatin and fluorouracil with additional cMab were consistent between the CD-DST and nude mice method using a clinically equivalent dose that reproduced human serum concentration [21]. Furthermore, Sakuma et al [15] reported that clinical efficacy can be predicted using clinical specimens obtained from biopsy. Therefore, the CD-DST can be used to evaluate the contact of PTX alone and in combination with cMab, which is useful for predicting clinical antitumor effects.…”

“…The collagen gel droplet-embedded culture drug sensitivity test (CD-DST), which was developed by Kobayashi et al [11], is an anticancer drug sensitivity test that combines three-dimensional (3D) microcarrier cell culture with serum-free medium and image-based colorimetric analysis [11]. This method has demonstrated high success rates for a wide range of diseases, including OSCC, by overcoming many the limitations of conven-tional chemosensitivity tests [12][13][14][15]. Because CD-DST uses a micro-3D culture, it can be used to evaluate OSCC and other cancers that have low tumor volume.…”

Establishment and Characterization of the Human Tongue Squamous Cell Carcinoma Cell Line NOKT-1

“…This method has advantages in that it allows testing using smaller quantities of cells compared with conventional assays. Furthermore, it eliminates the effects of fibroblasts that can adulterate samples at the time of harvesting and allows the evaluation of physiological drug concentrations [13][14][15][16] . In addition, the CD-DST method can be evaluated by combining multiple anticancer agents.…”

“…Similarly, as previously reported, sensitivity tests using cisplatin, fluorouracil, or docetaxel at OSCC showed a success rate of 81.8% in primary culture 15) . In addition, we conducted anticancer drug susceptibility tests, including those for cetuximab, using OSCC samples with success rates of 83.3% for primary tumors, 100% for metastatic lymph nodes, and 84.0% overall 16) .…”