Pilot Phase IIa Study of Metronomic Chemotherapy With Taxotere (Docetaxel) Plus Nexavar (Sorafenib) as First-Line Therapy in Performance Status-2 Patients With Advanced Non-Squamous Cell Non-Small Cell Lung Cancer
The median survival of untreated advanced stage NSCLC is 5-6 months (2,3). Patients with
poor performance status due to malignancy or co-morbidities have a poorer survival. This
group of patients is underrepresented in clinical trials and may not receive chemotherapy
due to fear of increased toxicities with systemic chemotherapy. The overall median survival
of patients with advanced NSCLC treated with first-line platinum-based doublets is less than
12 months (8 10 months) with a 1-year and 2-year survival rate of 33% and 11%, respectively
(4 6). No chemotherapy regimen has a significant advantage over the others in the treatment
of advanced NSCLC. Agents targeting epidermal growth factor receptor, matrix
metalloproteinase, farnesyl transferase, protein kinase C and retinoic X receptor have so
far shown no survival benefit in combination with chemotherapy in advanced NSCLC (7-13).
Docetaxel has activity in NSCLC in both first line and second line settings. In poor
performance status patients or elderly patients, single agent chemotherapy is recommended.
Weekly docetaxel administration is well tolerated and has lesser incidence of hematologic
toxicity with no difference in overall survival when compared to patients receiving higher
doses (75 mg/m2) q 3 weeks (14-18). There is an increased need for better strategies to
improve survival as well as reduce regimen related toxicity for this large group of
patients. The use of targeted therapy as well as low dose-protracted chemotherapy
(metronomic chemotherapy) needs evaluation as such therapies have a better toxicity profile.
Sorafenib (BAY 49-bursts of toxic maximum tolerated dose (MTD) chemotherapy interspersed
with long breaks, there is now a shift in thinking towards the view that more compressed or
accelerated schedules of drug administration using much smaller individual doses than the
MTD would be more effective; not only in terms of reducing certain toxicities, but perhaps
even in improving antitumor effect as well. Moreover, some of these dosing/scheduling
strategies are ideally suited to combining chemotherapeutic agents with many of the new
targeted biologic drugs. The most recent refinement of this concept is called "metronomic"
chemotherapy, which refers to the frequent administration of cytotoxic chemotherapeutic
agents at doses significantly below the MTD, with no prolonged drug-free breaks.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
2-month Progression-free Survival
Evaluation of the 2-month progression-free survival in poor performance status patients with non-squamous non-small cell lung cancer with the goal to improve 2-month progression free survival from 50% to 70%.
Francisco Robert, M.D.
University of Alabama at Birmingham
United States: Institutional Review Board
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