Functional Profiling to Select Chemotherapy in Untreated, Advanced or Metastatic Non-Small Cell Lung Cancer
Robert A. Nagourney 1,2, Jonathan B. Blitzer 1, Robert L. Shuman 1, Thomas J. Asciuto 1, Eknath A. Deo 1, Marylyn Paulsen 1, Robert L. Newcomb 3, Steve S. Evans 2
1. Memorial Medical Center of Long Beach, Todd Cancer Institute, Long Beach, CA
2. Rational Therapeutics, Long Beach, CA
3. Institute for Clinical & Translational Science, University of California, Irvine, CA
Abtract
Background Aim:
To assess the impact of drug selection upon the treatment of advanced and metastatic non-small cell lung cancer (NSCLC), we applied a functional platform that measures drug induced cell death in human tumor primary-culture micro-spheroids isolated from surgical specimens.
Patients and Methods:
At diagnosis, microspheroids isolated by mechanical and enzymatic disaggregation were examined for drug-induced cell-death by morphology and staining characteristics. Drugs were administered using standard protocols. Thirty-one patients, who received at least one cycle of therapy, were evaluable. All patients signed informed consent.
Results:
Twenty of 31 patients responded (64.5%). 1 completely and 19 partially, providing a two-fold improvement over historical control of 30% (p=0.00015), a median time to progression of 8.5 months and a median overall survival of 21.3 months.
Conclusion:
This functional platform is feasible and provides a favorable objective response rate, time to progression and survival in advanced, metastatic, untreated NSCLC, and warrants further evaluation.
Source: Anticaner Research October 2012 vol. 32 no. 10; 4454-4460
http://ar.iiarjournals.org/content/3...8-1ae7c0d554dc
http://www.rationaltherapeutics.com/...dfs/EVAPCD.pdf
Using only FDA-approved, standard lung cancer drugs available to all oncologists, this process of laboratory selection provided a 64.5 percent response rate – more than double the national average of 30 percent (p = 0.00015), well established in the literature. More importantly, the median overall survival of 21.3 months was nearly two-fold longer than the best results of 13.5 months reported for non-assay based standard treatments. Strikingly, among the Stage IV (metastatic) patients, there are several who remain alive approaching eight years since diagnosis.
Standard treatment protocols, administered in accordance with published results in thoracic oncology literature, included: Carboplatin & Paclitaxel (Taxol); Cisplatin & Navelbine (vinorelbine); Cisplatin & Gemzar (gemcitabine); Carboplatin & Gemzar; Carboplatin & Alimta (pemetrexed); Tarceva (erlotinib); Tarceva & Avastin (bevacizumab); Carboplatin & Taxol & Avastin; Cisplatin & Navelbine & Avastin; Taxol; Docetaxel (Taxotere); Navelbine; Taxotere & Gemzar; Campto (Irinotecan); Campto & Cisplatin.
To date, they are tracking a 100% response rate to Tarceva in the select populations; even patients who have not been found to carry recognized mutations.
Assay Results and Bayes' Theorem
http://cancerfocus.org/forum/showthread.php?t=3754