A phase II study of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced non-small cell lung cancer.

BACKGROUND: More than 50% of all advanced non-small cell lung cancer (NSCLC) is diagnosed in patients older than 65 years. Chemotherapy in elderly patients has not been standardized even though cisplatin-based chemotherapy has been used in patients with advanced NSCLC as primary therapy. We investigated the efficacy and safety of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced NSCLC. METHODS: Chemotherapy-naïve patients (age > or = 65 years) with stage IIIB or IV NSCLC were enrolled. Patients received docetaxel (75 mg/m(2) on D1) and carboplatin (AUC of 5mg/ml/min on D1) every 3 weeks. The end points included the response rate, progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: A total of 43 patients was enrolled between March 2005 and December 2008, and 38 patients were evaluable. The median age was 74 years old (range, 65-84 years) and 39 patients (90.6%) had an ECOG PS of 0 or 1. Squamous cell carcinoma was observed in 18 patients (41.8%) and 24 patients (55.8%) had an increased Charlson comorbidity index score (CCI > or = 1). The median number of treatment cycles was five (range, 1-8) and the relative dose intensity was 90.4% for docetaxel and 92.7% for carboplatin. The overall response rate was 46.5% (95% CI, 31.6-61.4) for with one complete response and 19 partial responses. The median follow-up duration was 14.4 months. The median PFS was 6.9 months (95% CI, 6.25-7.55) and the median OS was 13.1 months (95% CI, 10.20-16.07). The 1-year survival rate was 60%. In grade 3 or 4 hematological toxicities, neutropenia (37.2%), anemia (18.6%) and thrombocytopenia (4.6%) were shown. The non-hematological toxicities were tolerable. CONCLUSIONS: The combination chemotherapy with docetaxel and carboplatin was effective with tolerable toxicities in elderly patients with advanced non-small cell lung cancer.

Modulation of transcription by the peroxisome proliferator-activated receptor delta--binding RNA aptamer in colon cancer cells.

Peroxisome proliferator-activated receptor delta (PPAR-delta), one of three PPAR subtypes, is a lipid-sensing nuclear receptor that has been implicated in multiple processes, including inflammation and cancer. To directly establish the role of PPAR-delta in colon cancer development and progression, we selected high-affinity RNA aptamers and expressed them in several colon cancer cell lines. Nuclear-expressed aptamers efficiently inhibited PPAR-delta-dependent transcription from a synthetic peroxisome proliferator response element-driven luciferase reporter. PPAR-delta-specific aptamers suppressed transcription from natural promoters of vascular endothelial cell growth factor-A and cyclooxygenase-2. Moreover, vascular endothelial cell growth factor-A and cyclooxygenase-2 mRNA levels were significantly reduced by the PPAR-delta-specific aptamers in colon cancer cells. Most significantly, HCT116 colon cancer cells with high-level expression of PPAR-delta-specific aptamers exhibited a striking loss of tumorigenic potential. Further study on these RNA aptamers could provide an opportunity to modulate PPAR-delta-mediated colon cancer development and progression. Taken together, our results establish an important role for PPAR-delta in transcription of tumor-promoting genes, which can be specifically modulated by high-affinity RNA intramers in colon cancer cells. The RNA intramers may be further developed as specific inhibitors for cancer therapeutic strategies.