gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 123
Location: Pennsylvania
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 Posted: Tue Sep 20, 2005 12:36 am Post subject: Cell Culture Drug Resistance Testing |
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The below information has to do with "resistance" information (not sensitivity and resistance) for NSCLC. All available chemosensitivity assays are able to report drug "resistance" information. Resistance implies that when a patient's cancer cells are exposed to a particular chemotherapy agent in the laboratory, the cancer cells will continue to live and grow. Some chemosensitivity assays also are able to report drug "sensitivity" information. Sensitivity implies that when a patient's cancer cells are treated with a particular chemotherapy agent in the laboratory, that agent will kill the cancer cells or inhibit their proliferation.
The Possible Role of Chemoresistance Testing in the Era of Post Surgical Adjuvant Chemotherapy for Non-Small Cell Lung Cancer (NSCLC)
Ricardo S. Santos, M.D., Amit N. Patel, M.D., Clark T. Gamblin, M.D., Hiran C. Fernando, M.D., James D. Luketich, M.D., and Rodney J. Landreneau, M.D., University of Pittsburg Medical Center, Pittsburgh, PA. CHEST 2004 Meeting, 2004, Abstract #1188: 1
PURPOSE: The role of empiric adjuvant chemotherapy after complete resection of NSCLC (stage Ia-IIIa) is being increasingly recommended by medical oncologists. This opinion is based upon a less than 5% benefit in overall survival with an associated 23% major treatment related toxicity among patients undergoing empiric therapy. Specific resistance and sensitivity testing is routinely utilized in antibiotic management of serious infection. A link between in vitro chemotherapy resistance and clinical outcome has been seen in patients with ovarian and breast cancer. However, current medical oncologic practice for lung cancer continues to utilize empiric drug treatment regimens in spite of potentially variable patient responses to a particular drug. We analyzed the chemotherapy resistance patterns in a consecutive group of patients with completely resected NSCLC.
METHODS: The in vitro extreme chemotherapy resistance (EDRŪ) profiles were obtained utilizing the Oncotech (Orange County, CA) EDRŪ assay, in which live cultures of resected tumor cells are incubated with supra-pharmacologic doses of selected chemotherapy agents. Tumors demonstrating proliferation by radioactive thymidine uptake analysis during a three day incubation were considered resistant to the specific agent. Thirty-seven patients following complete resection of stage I(28), stage II(5), stage IIIA(4) NSCLC were evaluated. The percentage of patients with extreme drug resistance occurring with front line chemotherapy agents for NSCLC is shown below.
RESULTS: In vitro resistance patterns seen to first line chemotherapy: LR(%); MR(%); HR(%); MR or HR(%). Platinum=41%;33%;26%;59% Taxanes=47%;41%;13%;54% Etoposide= 46%;19%;35%;54% Gencitabine=26%;12%;64%;76% Navelbine=59%;31%;9%;40% (LR=Low resistance; MR=Moderate resistance; HR=High resistance) .
CONCLUSION: Moderate to high chemoresistance to what is considered "front line" chemotherapy agents for NSCLC is substantial. This should caution thoracic surgeons and medical oncologists against the empiric prescription of these agents as adjuvant therapies for completely resected NSCLC patients.
CLINICAL IMPLICATIONS: Clinical algorithms considering the chemoresistance patterns of the individual patient?s tumor should be formulated in the future in lieu of empiric adjuvant chemotherapy.
In Vitro Extreme Chemotherapy Resistance Patterns for Resected Non-Small Cell Lung Cancer
T. d'Amato1, *R. Landreneau2, *R. McKenna3, R. Santos2, R. Parker4 1University of California, San Diego, San Diego, CA, 2University of Pittsburgh Medical Center, Pittsburgh, PA, 3Cedar Sinai Medical Center, Los Angeles, CA, 4Oncotech Inc, Tustin, CA.Annals of Thoracic Surgery, 2005, Abstract #42: 1
BACKGROUND: Recent reports have suggested adjuvant chemotherapy offers a small but significant survival advantage for patients with completely resected Non-Small Cell Lung Cancer (NSCLC). Little is known of the prevalence of extreme chemotherapy drug resistance (EDR) for the individual NSCLC patient being considered for adjuvant therapy. The EDR assay (Oncotech, Tustin, CA) is highly predictive of clinical unresponsiveness to chemotherapy for ovarian, brain, and breast cancer. This chemo-resistance testing is becoming an increasingly popular way to predict treatment failure, choose alternative agents, and to potentially avoid unnecessary chemotherapy toxicity for patients with these cancers.
METHODS: A total of 3,042 NSCLC specimens were cultured using a soft-agar based proliferation assay and tested for resistance to supra-pharmacologic doses of either CISPLATIN (CPLAT), CARBOPLATIN (CARBO), PACLITAXEL (TAX), ETOPOSIDE (VP16), or DOXORUBICIN (DOXO). Using 3H-Thymidine uptake the percentage of cell-growth inhibition was used to determine extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR).
RESULTS: EDR or IDR to CPLAT in 1,409/2227 (63%), to CARBO in 1,056/1,565 (68%), to VP-16 in 1581/2505 (63%), and to DOXO in 1,101/1471 (75%) of NSCLC cultures.
CONCLUSIONS: Chemotherapy resistance is highly variable and individualized among NSCLC clinical cell cultures. This may account for the marginal results seen with empiric use of ?First Line? chemotherapy agents in the adjuvant setting. The use of viable tumor culture in vitro analysis for EDR to these agents should be considered when formulating a plan of adjuvant therapy for resected NSCLC. Future trials comparing patient survival following tailored versus empiric adjuvant therapy appear justified. |
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