title: In vitro-chemosensitivity test using the collagen gel droplet embedded culture drug test (CD-DST) for malignant pleural mesothelioma: possibility of clinical application.
abstract: OBJECTIVE
  An in vitro-chemosensitivity test using the collagen gel droplet embedded culture drug test (CD-DST), established by Kobayashi et al. (Jpn J Cancer Res 2001; 92: 203-10), has been widely used on various tumors. This study retrospectively evaluated its possibility of clinical application to patients with malignant pleural mesothelioma (MPM).
  
  
  METHODS
  CD-DST using 26 fresh specimens obtained by biopsy or surgery on MPM patients investigated in vitro responses to cisplatin (CDDP), carboplatin (CBDCA), doxorubicin (ADR), etoposide (VP-16), 5-fluoruracil (5-FU), gemcitabine (GEM), vinorelbine (VNR), irinotecan (SN-38), and docetaxel (TXT). Correlations between CD-DST data and clinical effects were then assessed for some MPM patients undergoing chemotherapy.
  
  
  RESULTS
  The rate of in vitro sensitivity to each chemoagent (N=tested number) was 35% for CDDP (N=23), 14% for CBDCA (N=21), 7% for ADR (N=15), 15% for VP-16 (N=13), 0% for 5-FU (N=15), 45% for GEM (N=11), 25% for VNR (N=8), 40% for SN-38 (N=5), and 44% for TXT (N=9). No difference was observed between CD-DST data of each chemoagent and histological type. Of these MPM patients, 14 clinical effects on 13 patients who underwent chemotherapy for primary or recurrent disease were reviewed in comparison with CD-DST data of each chemoagent. Among 10 chemotherapies including in vitro-sensitive chemoagents, 3 led to partial response (PR), and 7 resulted in four stable diseases (SDs) and 3 to progressive diseases (PDs). In contrast, among 4 chemotherapies using in vitro-resistant chemoagents, SD and PD were observed in 1 and 3, respectively. In regard to the clinical response rate, CD-DST sensitivity, specificity, and accuracy in the 14 examined chemotherapies were respectively 100%, 36%, and 50%, and in regard to the disease control rate, they were 88%, 60%, and 71%. CD-DST data for the chemoagents were to a limited extent significantly correlated with the disease control status of chemotherapy (p=0.052).
  
  
  CONCLUSIONS
  Although the number of tested MPM specimens was small, CD-DST data obtained by biopsy or surgical-fresh specimens of MPM marginally correlated to the disease control effect of chemotherapy for this disease. Therefore CD-DST may possibly be applied to selecting the chemotherapy regimen for MPM. To determine the possibility of a clinical application of this test to MPM, a prospective clinical study of a greater number of patients will be necessary.
authors.affiliation: Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Higashiyama
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Oda
authors.forename: Jiro
authors.initials: J
authors.lastname: Okami
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Ken
authors.initials: K
authors.lastname: Kodama
authors.forename: Koji
authors.initials: K
authors.lastname: Takami
authors.forename: Kenji
authors.initials: K
authors.lastname: Morinaga
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Takano
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D018579:Patient Selection; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005782:Gels; D003094:Collagen