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Ann Thorac Surg 2006;81:440-447
© 2006 The Society of Thoracic Surgeons

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Original article: General thoracic

Prevalence of In Vitro Extreme Chemotherapy Resistance in Resected Nonsmall-Cell Lung Cancer

^a University of Pittsburgh Medical Center, Presbyterian Shadyside, Heart, Lung and Esophageal Surgery Institute, Pittsburgh, Pennsylvania
^b Division of Thoracic and Foregut Surgery, Shadyside Medical Center, Pittsburgh, Pennsylvania
^c Cedar Sinai Medical Center, Division of Thoracic Surgery, Los Angeles, California
^d Oncotech, Inc, Tustin, California

Accepted for publication August 19, 2005.

^_* Address correspondence to Dr d'Amato, UPMC Presbyterian Shadyside, Heart, Lung and Esophageal Surgery Institute, Suite C800, 200 Lothrop St, Pittsburgh, PA 15213 (Email: damatota{at}upmc.edu).

Presented at the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.

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.

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				T. A. d'Amato, R. J. Landreneau, W. Ricketts, W. Huang, R. Parker, E. Mechetner, I.-R. Yu, and J. D. Luketich Chemotherapy resistance and oncogene expression in non-small cell lung cancer J. Thorac. Cardiovasc. Surg., February 1, 2007; 133(2): 352 - 363. [Abstract] [Full Text] [PDF]