Targeted and cytotoxic therapy in coordinated sequence (TACTICS): erlotinib, bevacizumab, and standard chemotherapy for non-small-cell lung cancer, a phase II trial.
ABSTRACT This trial focused on optimally combining existing targeted therapies and cytotoxic chemotherapy in the treatment of unselected patients with advanced non-small-cell lung cancer (NSCLC).
Patients with previously untreated advanced-stage nonsquamous NSCLC were eligible for this trial. In module A, patients received up to 4 cycles of erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks. Patients then received carboplatin (AUC = 6), paclitaxel 200 mg/m2, and bevacizumab 15 mg/kg for 4 cycles in module B. Patients who did not have progressive disease in module A received maintenance erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks in module C.
Forty-eight patients were enrolled in this multicenter phase II trial. Most patients were male (62.5%) and white (77.1%) with stage IV disease (93.8%) and adenocarcinoma histologic type (66.7%). The overall response rate in module A was 10.4%, in module B it was 15.1%, and in module C it was 5.5%. The study achieved its primary endpoint, with a nonprogression rate of 45.8% in module A. The median overall survival (OS) was 12.6 months.
The novel systemic therapy regimen is feasible in patients with advanced NSCLC. However there is no further role for developing this regimen in unselected patients with NSCLC.
- SourceAvailable from: Michael Tachezy[show abstract] [hide abstract]
ABSTRACT: The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR-625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFß1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers.PLoS ONE 01/2012; 7(6):e38248. · 3.73 Impact Factor