Prevalence of in vitro chemotherapeutic drug resistance in primary malignant pleural mesothelioma: result in a cohort of 203 resection specimens.
OBJECTIVE
Optimizing the multimodality treatment of malignant pleural mesothelioma depends on many factors including an adequate chemotherapeutic response. Currently, chemotherapy regimens for patients with mesothelioma are empirically selected. In vitro chemotherapy resistance in human mesothelioma has not been reported. Our goal was to determine the prevalence of drug resistance in a large sample of malignant pleural mesothelioma using a commercially available assay.


METHODS
Tumors specimens (n = 203) were cultured for analysis of chemoresistance using the extreme drug resistance assay. Evaluable results were obtained in 168 (168/203 = 83%) specimens. Each specimen was tested with 3 drugs: cisplatin, gemcitabine, and vinorelbine. Drug resistance was characterized as low, intermediate, or extreme. Median age was 64 years (30-85 years). Forty-four (26%) patients received neoadjuvant chemotherapy before sampling and testing. The distribution of histopathologic cell types was epithelial (103; 61%), mixed (57; 34%), and sarcomatoid (8; 5%).


RESULTS
A significant proportion of tumors had extreme/intermediate drug resistance to cisplatin (27%), gemcitabine (31%), or vinorelbine (59%). Nineteen tumors (11%) had extreme/intermediate resistance to all 3 drugs. Resistance (extreme/intermediate) to cisplatin was more prevalent in epithelial tumors than in nonepithelial (33% vs 18%; P = .0394). No significant differences in chemoresistance were found in tumors of patients who had received neoadjuvant chemotherapy compared with those who had not.


CONCLUSIONS
The feasibility of performing off-site in vitro drug resistance assays on resected malignant mesothelioma specimens is reported. A significant proportion of mesothelioma tumors exhibited extreme/intermediate resistance to cisplatin, gemcitabine, or vinorelbine.
Mujoomdar
Aneil A
AA
Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Tilleman
Tamara R
TR
Richards
William G
WG
Bueno
Raphael
R
Sugarbaker
David J
DJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000494:pharmacology*; D015331:Cohort Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005240:Feasibility Studies; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine