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

October 2012 Volume 4 Issue 4

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October 2012 Volume 4 Issue 4

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Article

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

Authors:
- Takumi Ochiai
- Kazuhiko Nishimura
- Tomoo Watanabe
- Masayuki Kitajima
- Akinori Nakatani
- Takashi Inou
- Marie Washio
- Naoki Sakuyama
- Tsuyoshi Sato
- Kenji Kishine
- Takanori Ochi
- Satoshi Okubo
- Shunji Futagawa
- Satomi Mashiko
- Isao Nagaoka
View Affiliations / Copyright

Affiliations: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo, Japan, Department of Pharmacy, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo, Japan, Department of Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo, Japan
Pages: 621-624
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Published online on: July 25, 2012

https://doi.org/10.3892/ol.2012.823
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Abstract

The leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) regimens with or without molecularly‑targeted drugs are widely used as first-line chemotherapy in the treatment of advanced colorectal cancer (CRC). Whether FOLFOX or FOLFIRI is administered first is not significant, however, it is essential that full administration of the targeted dosages of all 3 drugs, 5-FU, l-OHP and SN-38, is achieved. However, this is not always possible and second‑line chemotherapy must be abandoned in certain cases. Where possible, the most effective regimen should be selected as the first line of treatment. The aim of this study was to determine whether first-line chemotherapy may be individualized using the collagen gel droplet-embedded drug sensitivity test (CD-DST). Specimens of primary tumors were obtained from 43 CRC patients who had received no preoperative chemotherapy. Informed consent to measure drug sensitivity was obtained from all patients. The CD-DST allows evaluation of drug sensitivity using isolated, 3-dimensionally cultured tumor cells in a small collagen gel droplet. The CD-DST was performed and the growth inhibition rate (IR) was obtained under incubation conditions (5-FU with l-OHP at 6.0 and 3.0 µg/ml, or 5-FU with SN-38 at 6.0 and 0.2 µg/ml, respectively, for 24 h). The cumulative distributions of the growth IRs under each condition were evaluated based on the evidence that the clinical response rates to FOLFOX and FOLFIRI were almost the same. Individualization of first-line treatment was possible in all patients, with FOLFOX and FOLFIRI showing higher efficacy in 26 and 15 patients, respectively, and equal efficacy in 2 cases. This method has the potential to facilitate the establishment of individualized first-line chemotherapy for CRC and improve the prognosis in such patients.

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1.	A de GramontA FigerM SeymourLeucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancerJ Clin Oncol18293829472000
2.	RM GoldbergDJ SargentRF MortonA randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancerJ Clin Oncol222330200410.1200/JCO.2004.09.046
3.	ML RothenbergAM OzaRH BigelowSuperiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trialJ Clin Oncol2120592069200310.1200/JCO.2003.11.126
4.	JY DouillardD CunninghamAD RothIrinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomized trialLancet35510411047200010.1016/S0140-6736(00)02034-1
5.	C TournigandT AndréE AchilleFOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR studyJ Clin Oncol22229237200410.1200/JCO.2004.05.11314657227
6.	HS HochsterLL HartRK RamanathanSafety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE StudyJ Clin Oncol2135233529200810.1200/JCO.2007.15.413818640933
7.	LB SaltzS ClarkeE Díaz-RubioBevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III studyJ Clin Oncol2620132019200810.1200/JCO.2007.14.993018421054
8.	BJ GiantonioPJ CatalanoNJ MeropolBevacizumab in combination with oxaliplatin, fluorouracil and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the eastern cooperative oncology group study E3200J Clin Oncol2515391544200710.1200/JCO.2006.09.6305
9.	C BokemeyerI BondarenkoA MakhsonFluorouracil, leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancerJ Clin Oncol27663671200910.1200/JCO.2008.20.839719114683
10.	TS MaughanR AdamsCG SmithIdentification of potentially responsive subsets when cetuximab is added to oxaliplatin-fluoropyrimidine chemotherapy (CT) in first-line advanced colorectal cancer (aCRC)J Clin Oncol28Suppl 5abs. 35022010
11.	CS FuchsJ MarshallE MitchellRandomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C StudyJ Clin Oncol2547794786200710.1200/JCO.2007.11.3357
12.	E Van CutsemCH KöhneE HitreCetuximab and chemotherapy as initial treatment for metastatic colorectal cancerN Eng J Med36014081417200919339720
13.	A GrotheyD SargentRM GoldbergSurvival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan and oxaliplatin in the course of treatmentJ Clin Oncol2212091214200410.1200/JCO.2004.11.03715051767
14.	A GrotheyD SargentOverall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan and oxaliplatin regardless of whether doublet or single-agent therapy is used first lineJ Clin Oncol2394419442200510.1200/JCO.2005.04.4792
15.	T OchiaiK NishimuraT WatanabeLeucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan as individualized first-line therapy based on a drug sensitivity testExp Ther Med1325329201010.3892/etm_0000005022993545
16.	H KobayashiK TanisakaO DoiAn in vitro chemosensitivity test for solid tumors using collagen gel droplet embedded culturesInt J Oncol11449455199721528231
17.	H KobayashiM HigashiyamaK MinamigawaExamination of in vitro chemosensitivity test using collagen droplet culture method with colorimetric endpoint quantificationJpn J Cancer Res92203210200110.1111/j.1349-7006.2001.tb01083.x11223550
18.	E Van CutsemCH KöhneI LángCetuximab plus irinotecan, fluorouracil and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation statusJ Clin Oncol2920112019201121502544
19.	C BokemeyerI BondarenkoJT HartmannEfficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS studyAnn Oncol2215351546201110.1093/annonc/mdq63221228335
20.	JY DouillardS SienaJ CassidyRandomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME studyJ Clin Oncol2846974705201010.1200/JCO.2009.27.4860
21.	M KoopmanS VenderboschH van TinterenPredictive and prognostic markers for the outcome of chemotherapy in advanced colorectal cancer, a retrospective analysis of the phase III randomized CAIRO studyEur J Cancer4519992006200910.1016/j.ejca.2009.04.01719457654
22.	M KoopmanS VenderboschID NagtegaalJH van KriekenCJ PuntA review on the use of molecular markers of cytotoxic therapy for colorectal cancer, what have we learned?Eur J Cancer4519351949200910.1016/j.ejca.2009.04.02319473832
23.	T OchiaiK NishimuraH NoguchiPrognostic impact of orotate phosphoribosyl transferase among 5-fluorouracil metabolic enzymes in resectable colorectal cancers treated by oral 5-fluorouracil-based adjuvant chemotherapyInt J Cancer11830843088200610.1002/ijc.21779
24.	T OchiaiK NishimuraT WatanabeEvaluation of the individual 50% inhibitory area under the concentration curve of 5-fluorouracil based on the collagen gel droplet embedded culture drug sensitivity test in colorectal cancerMol Med Rep24054092009
25.	T OchiaiK NishimuraT WatanabePersonalized adjuvant chemotherapy for colorectal cancer (CRC) based on an individual 50% inhibitory area under the concentration curve (AUC) using collagen gel droplet embedded culture-drug sensitivity test (CD-DST)J Clin Oncol28Suppl 15abs. 35822010
26.	MS BraunSD RichmanP QuirkePredictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trialJ Clin Oncol2626902698200810.1200/JCO.2007.15.558018509181
27.	H MinamiK SaiM SaekiIrinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A16 and 28Pharmacogenet Genomics17497504200717558305
28.	Y AndoH SakaM AndoPolymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysisCancer Res6069216926200011156391
29.	K SaiJ SawadaH MinamiIrinotecan pharmacogenetics in Japanese cancer patients: roles of UGT1A1 6 and 28Yakugaku Zasshi1285755842008(In Japanese)
30.	MT SeymourFluorouracil, oxaliplatin and CPT-11 (irinotecan), use and sequencing (MRC FOCUS): a 2135-patient randomized trial in advanced colorectal cancer (ACRC)J Clin Oncol23Suppl 16abs. 35182005
31.	CH KöhneE Van CutsemJ WilsPhase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European organization for research and treatment of cancer gastrointestinal group study 40986J Clin Oncol23485648652005

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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