Survival Among Patients with Platinum Resistant, Locally Advanced Non-Small Cell Lung Cancer Treated with Platinum-Based Systemic Therapy
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Recent adjuvant chemotherapy trials after resection of stage II and III non-small cell lung cancer (NSCLC) have identified important survival differences among patients with immunohistochemical evidence suggesting platinum resistance. No clinical information exists regarding the impact upon survival of patients treated with platinum agents who exhibit cellular evidence of their tumors’ resistance to platinum. We evaluated the utility of the extreme drug resistance (EDR) assay to predict mortality among a consecutive group of stage II through IV NSCLC patients receiving adjuvant or definitive platinum-based chemotherapy after resection or surgical biopsy.
The Extreme Drug Resistance (EDR) Assay is a clinically validated cellular proliferation assay used to test tumors for chemotherapy drug resistance. Based on response in the EDR assay, tumor specimens from stage II through IV NSCLC patients were segregated into three groups: extreme drug resistant (EDR), intermediate drug resistant (IDR), and low drug resistant (LDR). Patient survival was evaluated after platinum-based chemotherapy.
Platinum IDR/EDR was statistically significant in predicting shorter overall survival (29.8 months vs. 15.6 months) among platinum IDR/EDR-resistant patients compared with LDR patients (P = 0.047). Median survival was 16.6 months for patients with IDR/EDR to platinum and any other second agent of doublet therapy compared with patients with LDR to any platinum-based doublet where median survival was not achieved (P = 0.0268).
This is the first study to demonstrate the utility of the EDR assay to predict poor clinical outcome when platinum-based therapy is used to treat patients with biological evidence of tumor resistance to platinum. These data corroborate the finding of recent studies evaluating possible molecular correlates to poor response to specific chemotherapeutic agents.
KeywordsEpidermal Growth Factor Receptor Chemotherapy Resistance Platinum Agent Tumor Biopsy Specimen Doublet Therapy
- 1.American Cancer Society. Cancer facts & figures 2008. American Cancer Society, Atlanta, 2008.Google Scholar
- 4.Douillard J, Rosell R, Delena M, et al. ANITA: phase III adjuvant vinorelbine (N) and cisplatin (P) versus observation (OBS) in completely resected (stage I–III) non-small-cell lung cancer (NSCLC) patients (pts): final results after 70-month median follow-up. On behalf of the Adjuvant Navelbine International Trialist Association. ASCO annual meeting proceedings, Orlando, Florida, USA. J Clin Oncol. 2005;23:7013.Google Scholar
- 11.Greene FL, Page DL, Fleming ID, et. al. AJCC cancer staging manual, 6th ed. Springer-Verlag, New York, 2002.Google Scholar
- 23.Schwartz AM, Henson DE. Diagnostic surgical pathology in lung cancer: ACCP evidence-based clinical practice guidelines, 2nd ed. Chest. 2007;132(3 Suppl):78S–93S.Google Scholar
- 25.Strauss G, Herndon J, Maddaus M, et al. Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633. ASCO Annual Meeting Proceedings Part I. J Clin Oncol. 2006;24(18S):7007.Google Scholar