A pilot study of docetaxel and trofosfamide as second-line 'metronomic' chemotherapy in the treatment of metastatic non-small cell lung cancer (NSCLC).

BACKGROUND: The aim of this pilot study was to evaluate the efficacy and safety of a chemotherapy containing docetaxel and oral trofosfamide as a 'metronomic' secondline treatment of patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: 21 patients with stage IV disease NSCLC who had progressed under first-line chemotherapy were enrolled. Previous chemotherapy was platinum-based in 15 patients (71.4%), whereas 6 patients (28.6%) had received platinum-free combination chemotherapy. Patients received docetaxel 25 mg/m(2) on days 1, 8, and 15 every 4 weeks plus trofosfamide 50 mg per day. RESULTS: A total of 62 chemotherapy cycles were administered. The median number of cycles per patient was 3. The overall response rate to chemotherapy was 19%, median overall survival was 6.9 months, the median progression-free survival 2.9 months, the 1-year survival rate 28.6%, and the 2-year survival rate 7.1%. No grade IV toxicity was observed. CONCLUSIONS: Our results suggest that the combination of docetaxel and trofosfamide in a metronomic schedule is active and well tolerable as second-line therapy in patients with metastatic NSCLC. The concept of metronomic chemotherapy promises to be a valuable addition to the existing treatment options in NSCLC and warrants further investigation in phase III studies.

Serum levels of Magic Roundabout protein in patients with advanced non-small cell lung cancer (NSCLC).

BACKGROUND: Magic Roundabout (MR; ROBO 4) is a recently discovered gene which encodes a protein that derived its name form the structural homology with the roundabout family of genes. Genes of the roundabout family comprise neuronal-specific cell surface receptors that are involved in axon guidance. MR in contrast showed endothelial specificity in vitro and in vivo using immunohistochemistry and in situ hybridisation. The putative role of MR as an endothelial analogue of Roundabout in angiogenesis makes it an attractive target for anti-angiogenic cancer therapy. PATIENTS AND METHODS: Using specific antibodies against MR peptide, we screened pretreatment sera from 193 patients with advanced non-small cell lung cancer (NSCLC) for MR-protein levels. RESULTS: Patients with serum levels of MR-protein lower than median (E(450 nm) = 0.652) had a median survival of 41.0 weeks whereas those with a higher serum level had a considerably shorter median survival of 32.4 weeks (P = 0.05). The pretreatment serum level of MR-protein achieved no significance in a univariate Cox regression analysis. CONCLUSIONS: This is the first study to present clinical data that link MR expression with outcome in patients with NSCLC, whether the correlation of pretreatment serum levels of MR and survival can be attributed to MR dependent angiogenesis remains to be investigated.