Primary Outcome Measures:
- To assess the overall progression-free survival (PFS) in patients with advanced or metastatic (Stage IIIB - pleural effusion/IV), non-squamous histology NSCLC treated with metronomic chemotherapy plus Avastin. [ Time Frame: % of patients progression -free at 6 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 2.2.4 Assessment of circulating endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) by flow cytometry as a surrogate marker of the anti-angiogenic effect of Avastin-based metronomic therapy. [ Time Frame: Day 1, cycle 1; Day 1 cycle 3, 6 ] [ Designated as safety issue: No ]
- To assess toxicity in patients with advanced or metastatic (Stage IIB - pleural effusion/IV), non-squamous histology NSCLC treated with metronomic chemotherapy plus Avastin. [ Time Frame: No time frame for toxicities experienced. ] [ Designated as safety issue: Yes ]
- To determine blood levels of VEGF, soluble VEGFR2, thrombospondin-1, E-selectin and ICAM-1 before and during therapy, and explore possible correlations with clinical outcome. [ Time Frame: Prior to and during therapy ] [ Designated as safety issue: No ]
This is a non-randomized, open-label, pilot Phase II study of metronomic chemotherapy plus Avastin in chemo naïve subjects with advanced non-squamous, non-small cell carcinoma of the lung. The primary endpoint of this study is to assess the overall progression-free survival.
Subjects will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks, and Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy will be expressed as a 4-week cycle. Tumor response to treatment will be evaluated every 8 weeks.
Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will then continue until disease progression, intolerable toxicity or withdrawal of consent.
Potential biologic parameters to monitor anti-tumor activity of metronomic chemotherapy will be evaluated in 10 subjects. These biomarkers include: sequential determination of blood levels of VEGF, VEGFR2, thrombespondin-1, E-selectin, ICAM-1, and circulating endothelial cells and endothelial precursor cells.