Adenosine triphosphate‐based chemotherapy response assay (ATP‐CRA)‐guided platinum‐based 2‐drug chemotherapy for unresectable nonsmall‐cell lung cancer

Abstract

BACKGROUND.The study investigated correlations between adenosine triphosphate / chemotherapy response assay (ATP‐CRA) and clinical outcomes after ATP‐CRA‐guided platinum‐based chemotherapy for unresectable nonsmall‐cell lung cancer (NSCLC).METHODS.The authors performed an in vitro chemosensitivity test, ATP‐CRA, to evaluate the chemosensitivities of anticancer drugs such as cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine for chemonaive, unresectable NSCLC. The cell death rate was determined by measuring the intracellular ATP levels of drug‐exposed cells compared with untreated controls. A sensitive drug was defined as a drug producing 30% or more reduction in ATP compared with untreated controls. Assay‐guided platinum‐based 2‐drug chemotherapy was given to patients with pathologically confirmed NSCLC.RESULTS.Thirty‐four patients were enrolled. Thirty tumor specimens were obtained by bronchoscopic biopsies and 4 obtained surgically. The median age was 61 years and 27 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. The response rate was 43.8%. At a median follow‐up period of 16.9 months, the median progression‐free and overall survivals were 3.6 and 11.2 months, respectively. Patients were dichotomized into the platinum‐sensitive (S; 20 patients) and resistant (R; 14 patients) groups. The positive/negative predictive values were 61.1% and 78.6% with a predictive accuracy of 68.8%. Although without significant differences in pretreatment parameters, the S‐group showed better clinical response (P = .036), longer progression‐free survival (P = .060), and longer overall survival (P = .025).CONCLUSIONS.Despite using bronchoscopic biopsied specimens, ATP‐CRA and clinical outcomes correlated well after assay‐guided platinum‐based 2‐drug chemotherapy for unresectable NSCLC. There was a favorable response and survival in the platinum‐sensitive vs resistant groups. Cancer 2007. © 2007 American Cancer Society.

ATP assay-guided chemosensitivity testing for gemcitabine with biopsy specimens obtained from unresectable pancreatic cancer using endoscopic ultrasonography-guided fine-needle aspiration

“…However, as new agents and chemotherapy regimens are accepted for various kinds of cancers in clinical situations, new sensitivity criteria should be defined. With regard to gemcitabine, 16.9 lg/ml gemcitabine concentration and greater than 30% inhibition (inhibition rate = 100 -T/C ratio; in other words, T/C ratio less than 70%) was reported as the sensitivity criterion for advanced non-small cell lung cancer [7]. In this study, gemcitabine concentration was 20 lg/ml, according to the peak plasma concentration of gemcitabine [19], but similar Fig.…”

“…If the T/C ratio is low, we expect good therapeutic efficacy. The usefulness of chemosensitivity testing has been reported for various cancers, for example those of the gastrointestinal tract, lung, ovary, and breast, and malignant melanoma [5][6][7][8][9][10]. For gastric cancer, especially, the reported sensitivity, specificity, and accuracy of chemosensitivity testing are, respectively, 82.7, 70.7, and 73.6% [11].…”

Purinergic Signaling in the Airways

“…ATP-based chemotherapy response assay has been used to guide the outcome of platinum-based drug chemotherapy for nonresectable non-small-cell lung cancer (Moon et al, 2007(Moon et al, , 2009. It has been suggested that tumor-infiltrating immune cells can benefit the tumor by producing factors that promote angiogenesis and suppress immunity; adenosine levels are high in tumors.…”

ATP-Based Chemotherapy Response Assay in Patients with Unresectable Gastric Cancer

“…ATP-based ITRT determines the degree of cell inhibition by comparing the ATP remaining in the test compared to the control wells to predict the response to each chemotherapeutic agent. Recently, an ATP-based chemotherapy response assay (ATP-CRA), a modified form of the ATP-based ITRT, has been proven to be useful in lung and breast cancer [2,3] . Since results can be obtained from a small amount of tissue in a short period of time, the ATP-CRA enables to accelerate treatment initiation to meet clinical requirements.…”