Prevalence of in vitro extreme chemotherapy resistance in resected nonsmall-cell lung cancer.
BACKGROUND
Recent clinical trials suggest that adjuvant chemotherapy provides a survival advantage for patients with completely resected nonsmall-cell lung cancer (NSCLC) yet many patients receive chemotherapy without benefit. Tumor in vitro resistance to antineoplastic agents is highly predictive of clinical unresponsiveness to chemotherapy for some cancers; however, little is known of the prevalence of extreme chemotherapy drug resistance for human NSCLC tumors. Chemoresistance testing may be a way to predict treatment failure, choose alternative agents, and to avoid unnecessary chemotherapy toxicity. This study describes the prevalence of in vitro chemotherapy resistance in NSCLC patient tumor cultures.


METHODS
A total of 3,042 NSCLC specimens were cultured in a proliferation assay and tested for resistance to carboplatin, cisplatin, doxorubicin, etoposide, gemcitabine, navelbine, paclitaxel, taxotere, or topotecan. The percentage of cell-growth inhibition measured by 3H-Thymidine uptake was used to determine extreme drug resistance, intermediate drug resistance, or low drug resistance.


RESULTS
Extreme drug resistance or intermediate drug resistance to carboplatin was found in 1,056 of 1,565 NSCLC cultures (68%), to cisplatin in 1,409 of 2,227 (63%), to doxorubicin in 1,101 of 1,471 (75%), to etoposide in 1,581 of 2,505 (63%), to gemcitabine in 594 of 823 (72%), to navelbine in 603 of 1,444 (42%), to paclitaxel in 689 of 1,706 (40%), to taxotere in 273 of 521 (52%), and to topotecan in 280 of 896 (31%).


CONCLUSIONS
Chemotherapy resistance is prevalent among NSCLC clinical cell cultures. This may account for the small survival seen with empiric adjuvant chemotherapy. The use of viable tumor culture for in vitro chemoresistance testing should be considered when formulating a plan of adjuvant therapy for resected NSCLC. Future trials comparing patient survival after tailored versus empiric adjuvant therapy appear justified.
d'Amato
Thomas A
TA
Presbyterian Shadyside, Heart, Lung and Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. damatota@upmc.edu
Landreneau
Rodney J
RJ
McKenna
Robert J
RJ
Santos
Ricardo S
RS
Parker
Ricardo J
RJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
D000970:Antineoplastic Agents