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.
The in vitro extreme chemotherapy resistance (EDR) profiles were obtained utilizing the Oncotech (Orange County, CA) EDR 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 are shown below.
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) .
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 algorithms considering the chemoresistance patterns of the individual patient’s tumor should be formulated in the future in lieu of empiric adjuvant chemotherapy.
R.S. Santos, None.