Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test

Ochiai, Takumi; Nishimura, Kazuhiko; Watanabe, Tomoo; Kitajima, Masayuki; Nakatani, Akinori; Inou, Takashi; Washio, Marie; Sakuyama, Naoki; Sato, Tsuyoshi; Kishine, Kenji; Ochi, Takanori; Okubo, Satoshi; Futagawa, Shunji; Mashiko, Satomi; Nagaoka, Isao

doi:10.3892/ol.2012.823

Cited by 8 publications

(8 citation statements)

References 32 publications

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“…Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) uses an image colorimetric method to assess the combination of an anticancer drug and microcollagen gel embedded in a three-dimensional serum-free culture medium (3 to 10x10 3 cells/30 µg/drop) (5,6). It is a susceptibility test that is currently widely applied in various clinical fields, including gastrointestinal cancer (7)(8)(9). However, reports on the use of CD-DST in OSCC were few and none have evaluated multidrug combination chemotherapy or IACRT.…”

Section: Introductionmentioning

confidence: 99%

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

et al. 2017

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Abstract. Using trace three-dimensional culture, the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) can be tested even in cases with a small number of cells, including oral squamous cell carcinoma (OSCC), and evaluation of the antitumor effect with a drug concentration close to the in vivo level is possible. The present report aimed to evaluate the utility of the CD-DST in the assessment of the in vitro efficacy of single-agent and multidrug combination chemotherapy for OSCC in comparison with the clinical response rates and to examine the possible clinical application of CD-DST for such cases. A total of 33 OSCC patients from whom 33 samples were obtained from January 2010 to September 2015 were included. CD-DST was performed, individually and in combination, on the three drugs [i.e., cisplatin (CDDP), 5-fluorouracil (5-FU), and docetaxel (DOC)] and on super selective intra-arterial infusion chemoradiotherapy (IACRT). The overall evaluable rate of the CD-DST in OSCC was 81.8% (27 of 33 cases) and the sensitivity to each anticancer drug was evaluated. The in vitro efficacy rates of IACRT, cisplatin + 5-fluorouracil, and docetaxel + cisplatin + 5-fluorouracil (TPF) confirmed the estimated clinical response rates. In 14 of 33 patients, the results of CD-DST were compared with clinical efficacy, which was judged based on measurable lesions on imaging. For TPF therapy, the sensitivity test of the IACRT had a positive predictive value of 90.9% (10 of 11 cases) and a negative predictive value of 100% (3 of 3 cases); the accuracy of the susceptibility test for the anticancer agents was 92.8% (13 of 14 cases). The CD-DST may be useful in selecting multidrug combination chemotherapy and IACRT for OSCC, however, accumulation of further clinical data is required in the future. IntroductionThe treatment of advanced or unresectable oral squamous cell carcinoma (OSCC) is multidisciplinary and entails the use of both multidrug combination chemotherapy and radiotherapy (1-3). The usefulness of super selective intraarterial infusion chemoradiotherapy (IACRT) to deliver high concentrations of anticancer drugs to tumors has been reported (4). The selection of such anticancer drugs for IACRT had been based on statistical information and clinical reports on a number of cases (1-3); however, the expected therapeutic effects of these anticancer drugs have not been consistent and adverse events were common. Therefore, drug sensitivity testing prior to administration of an anticancer agent is ideal to avoid the serious side effects of less effective anticancer drugs. Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) uses an image colorimetric method to assess the combination of an anticancer drug and microcollagen gel embedded in a three-dimensional serum-free culture medium (3 to 10x10 3 cells/30 µg/drop) (5,6). It is a susceptibility test that is currently widely applied in various clinical fields, including gastrointestinal cancer (7-9). However, reports on the use of CD-DST in OSCC were few a...

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Section: Introductionmentioning

confidence: 99%

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

et al. 2017

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“…HDRA is an anticancer drug sensitivity test using 3D cell culture, but it entails problems such as the requirement for a large number of cells and the influence of contaminating fibroblasts. In contrast, CD-DST is capable of analyzing a small number of cells (1x10 5 ) in 3D cell cultures that create an environment close to that of the body and is unaffected by contaminating fibroblasts, thus achieving high positive and negative predictive values (2,3).…”

Section: Discussionmentioning

confidence: 99%

“…CD-DST has little effect on non-cancerous cells, allowing accurate measurements of cancerous cells only. This method has been primarily used on tumors of the digestive system (4)(5)(6). Compared to such cancers of the primary organs, OSCC and other oral cancers generally have a smaller tumor volume.…”

Section: Introductionmentioning

confidence: 99%

Collagen gel droplet-embedded culture drug sensitivity testing in hard palate cancer-predicted antitumor efficacy of cetuximab: A case report

Sakuma

Tamura

Noda

et al. 2017

Molecular and Clinical Oncology

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Abstract.In vitro anticancer drug sensitivity assessments have been performed for various types of cancer, and an association with clinical response has been observed. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is an in vitro anticancer drug sensitivity test that has recently reported to be useful in oral squamous cell carcinoma (OSCC). CD-DST allows for the analysis of a smaller number of cells compared with other anticancer drug sensitivity tests. The present study reported a successful analysis of anticancer drug sensitivity using CD-DST on cervical lymph node tissue dissected following neoadjuvant chemotherapy from a 55-year-old man with advanced hard palate cancer. Tumor resection and bilateral neck dissection were performed following neoadjuvant chemotherapy (docetaxel + cisplatin + 5-fluorouracil; TPF) for hard palate cancer T2N2cM0. Local recurrence and cervical multiple skin metastasis occurred ~8 months after surgery, and the patient received six doses of cetuximab (C-mab) + cisplatin + 5-fluorouracil (C-mab + PF) administration, which is a type of molecular-targeted therapy. Following the use of the CD-DST method, the clinical response was noted as stable disease following execution of TPF and partial response following execution of C-mab + PF. In addition, low sensitivity by TPF and high sensitivity by C-mab + PF were reported. The CD-DST method reflected the clinical response for the patient, and the results of the current study indicate that CD-DST is a useful tool for selecting chemotherapeutic drugs for patients with OSCC. IntroductionThe recent introduction of the anticancer drug cetuximab [an epidermal growth factor receptor (EGFr) inhibitor: C-mab] as a molecular-targeted therapy for treating head and neck cancers has expanded the scope of anticancer drugs for treating these cancers. However, no biomarkers are currently available that can predict C-mab efficacy against oral squamous cell carcinoma (OSCC); therefore, it is typically administered irrespective of patient sensitivity (1). Hence, we investigated C-mab use with the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). Kobayashi et al (2,3) developed CD-DST which combines the collagen gel droplet culture method, a simple method of three-dimensional (3D) culture that allows a very small number of clinical samples to be tested with a serum-free medium step and quantitative evaluation by image analysis. CD-DST has little effect on non-cancerous cells, allowing accurate measurements of cancerous cells only. This method has been primarily used on tumors of the digestive system (4-6). Compared to such cancers of the primary organs, OSCC and other oral cancers generally have a smaller tumor volume. CD-DST is, therefore, likely to be a suitable method for testing the sensitivity of anticancer drugs on OSCC. However, there is little application of the CD-DST method to OSCC, with no evaluation of molecularly targeted drugs. In the present study, the CD-DST method was performed using a patient biops...

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“…In the past 20 years, an in vitro chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), has been developed on the basis of examinations of various types of malignant tumor at our ( 16 , 17 ) and other ( 18 – 20 ) institutions. Our group has subjected surgically resected samples to this test in order to aid the selection of effective chemotherapy regimens for patients with NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients with p-stage IIIA non-small cell lung cancer that underwent complete resection

Akazawa

Higashiyama

Nishino

et al. 2017

Molecular and Clinical Oncology

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The impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients undergoing complete resection for locally advanced non-small cell lung cancer (NSCLC) has yet to be elucidated. In the present study, the utility of adjuvant chemotherapy based on the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in patients with p (pathology)-stage IIIA NSCLC was retrospectively analyzed. A series of 39 patients that had received platinum-based adjuvant chemotherapy following complete resection between 2007 and 2012 were enrolled. Their surgical specimens were subjected to the CD-DST. The patients were subsequently classified into two groups on the basis of in vitro anti-cancer drug sensitivity data obtained using the CD-DST: The sensitive group (25 patients) were treated with regimens including one or two of the anti-cancer drug(s) that were indicated to be effective by the CD-DST, whereas the non-sensitive group (14 patients) were treated with chemotherapy regimens that did not include any CD-DST-selected anti-cancer drugs. There were no significant differences in the background characteristics of the two groups [including in respect of the pathological TN (tumor-lymph node) stage, tumor histology, epidermal growth factor receptor mutation status, the frequency of each chemotherapy regimen, and the number of administered cycles]. The 5-year disease-free survival (DFS) rate of the sensitive group was 32.3%, whereas that of the non-sensitive group was 14.3% (P=0.037). In contrast, no difference in overall survival (OS) was observed (P=0.76). Multivariate analysis revealed that adjuvant chemotherapy based on the CD-DST had a significant favorable effect on the DFS (P=0.01). Therefore, the present study has demonstrated that CD-DST data obtained from surgical specimens aid the selection of effective platinum-based adjuvant chemotherapy regimens for patients undergoing complete resection for p-stage IIIA NSCLC. The use of CD-DST-guided platinum-based regimens may have a beneficial impact on the DFS of such patients.

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Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test

Cited by 8 publications

References 32 publications

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

Clinical study on collagen gel droplet-embedded culture drug sensitivity test for multidrug combination chemotherapy and super selective intra-arterial infusion chemoradiotherapy in oral squamous cell carcinoma

Collagen gel droplet-embedded culture drug sensitivity testing in hard palate cancer-predicted antitumor efficacy of cetuximab: A case report

Impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients with p-stage IIIA non-small cell lung cancer that underwent complete resection

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