Prediction of chemotherapeutic effect on postoperative recurrence by in vitro anticancer drug sensitivity testing in non-small cell lung cancer patients.
OBJECTIVE
The collagen gel droplet embedded culture drug test (CD-DST), is an in vitro anticancer drug sensitivity test. The test has been used with various types of malignant tumors, but the significance of clinical application remains unknown. The aim of the present study is to evaluate the ability of this test to predict the response to chemotherapy in non-small cell lung cancer (NSCLC) patients.


METHODS
From January 2000 through March 2007, CD-DST data using the primary tumor specimens to anticancer drugs such as cisplatin (CDDP), carboplatin (CBDCA), paclitaxel (PAC), docetaxel (TXT), gemcitabine (GEM), and vinorelbine (VNR), was successfully obtained from 382 patients that underwent a radical resection for NSCLC. Eighty-one of those patients received 1st line chemotherapy using a "new generation" of anticancer drugs for postoperative recurrence. The chemotherapy regimen consisted of a CDDP (or CBDCA)-based combination (N=41), non-CDDP-based combination (N=1) and single agent (N=39). The predictability of the chemotherapeutic effect by the CD-DST data was analyzed retrospectively.


RESULTS
Partial response (PR) was obtained in 24 patients (response rate=30%), stable disease (SD) in 33 (41%) and progressive disease (PD) in 24 (30%). Forty-two patients underwent chemotherapy with one or more CD-DST-sensitive drugs, 21 of whom showed PR (RR=50%), whereas only 3 (8%) patients showed PR with chemotherapy with regimen including no CD-DST-sensitive drugs. Good predictability was obtained, with a 50% positive predictive value (PPV) for PR and a 92% negative predictive value (NPV) by CD-DST. The predictive accuracy for the response based on the CD-DST data was 70%. Interestingly, a subset analysis according to recurrence site showed that the predictive accuracy was highest (86%) for CD-DST-based chemotherapy for recurrence in the lymph nodes.


CONCLUSIONS
The application of the CD-DST for "new generation" anticancer drugs using surgically resected specimens of primary lesion in NSCLC patients may be clinically useful in the prediction of the response to chemotherapy for postoperative recurrence. CD-DST-oriented chemotherapy for postoperative recurrence especially in the lymph nodes may therefore be promising for the improvement of the treatment outcome.
Higashiyama
Masahiko
M
Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan. higasiyama-ma@mc.pref.osaka.jp
Oda
Kazuyuki
K
Okami
Jiro
J
Maeda
Jun
J
Kodama
Ken
K
Imamura
Fumio
F
Minamikawa
Kazuhiko
K
Takano
Toshikazu
T
Kobayashi
Hisayuki
H
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin