J Korean Med Sci.  2010 May;25(5):684-690. 10.3346/jkms.2010.25.5.684.

Individualized Tumor Response Testing for Prediction of Response to Paclitaxel and Cisplatin Chemotherapy in Patients with Advanced Gastric Cancer

Affiliations
  • 1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 2Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
  • 3Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Korea.
  • 4Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul, Korea.
  • 5Department of Internal Medicine, Seoul Paik Hospital, Seoul, Korea.
  • 6Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
  • 7Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. bangyj@snu.ac.kr
  • 8Isu Abxis Co., Ltd, Seoul, Korea.

Abstract

The purpose of our study was to determine the most accurate analytic method to define in vitro chemosensitivity, using clinical response as reference standard in prospective clinical trial, and to assess accuracy of adenosine triphosphate-based chemotherapy response assay (ATP-CRA). Forty-eight patients with chemo-naive, histologically confirmed, locally advanced or metastatic gastric cancer were enrolled for the study and were treated with combination chemotherapy of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 for maximum of six cycles after obtaining specimen for ATP-CRA. We performed the receiver operator characteristic curve analysis using patient responses by WHO criteria and ATP-CRA results to define the method with the highest accuracy. Median progression free survival was 4.2 months (95% confidence interval [CI]: 3.4-5.0) and median overall survival was 11.8 months (95% CI: 9.7-13.8) for all enrolled patients. Chemosensitivity index method yielded highest accuracy of 77.8% by ROC curve analysis, and the specificity, sensitivity, positive and negative predictive values were 95.7%, 46.2%, 85.7%, and 75.9%. In vitro chemosensitive group showed higher response rate (85.7% vs. 24.1%) (P=0.005) compared to chemoresistant group. ATP-CRA could predict clinical response to paclitaxel and cisplatin chemotherapy with high accuracy in advanced gastric cancer patients. Our study supports the use of ATP-CRA in further validation studies.

Keyword

Stomach neoplasms; Antineoplastic Agents; Therapeutic Use; Drug Screening Assays, Antitumor; Paclitaxel; Cisplatin; Sensitivity and Specificity

MeSH Terms

Adenosine Triphosphate/*analysis
Adult
Aged
Antineoplastic Agents, Phytogenic/administration & dosage
Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
Cisplatin/administration & dosage
Drug Screening Assays, Antitumor/*methods
Female
Humans
Korea
Male
Middle Aged
Outcome Assessment (Health Care)/methods
Paclitaxel/administration & dosage
Reproducibility of Results
Sensitivity and Specificity
Stomach Neoplasms/*diagnosis/*drug therapy/metabolism
Treatment Outcome
Antineoplastic Agents, Phytogenic
Cisplatin
Paclitaxel
Adenosine Triphosphate

Figure

  • Fig. 1 Receiver operating characteristic curve of ATP-chemotherapy response assay using ×1 and ×5 times test drug concentrations of paclitaxel and cisplatin.

  • Fig. 2 Progression free and overall survival of in vitro sensitive versus in vitro resistant patients. (A) Progression free survival. (B) Overall survival.


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