Metronomic antiangiogenetic biochemotherapy of non-small cell lung cancer patients ....

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Sub-category: Metastatic Lung Cancer
Category: Lung Cancer--Metastatic Lung Cancer
Meeting: 2009 ASCO Annual Meeting
Citation: J Clin Oncol 27, 2009 (suppl; abstr e19083)
Abstract No: e19083
Author(s): C. Remondo,
C. Migali, I. Martellucci, F. Carbone, V. Ricci, R. Addeo, S. Del
Prete, F. Fulfaro, G. Francini, P. Correale; Medical Oncology Siena
University, Siena, Italy; Radiology, Siena, Italy; Medical Oncology
Section, Frattaminore, Italy; University of Palermo, Palermo, Italy
Background: Chemotherapy
efficacy in advanced non small cell lung cancer (NSCLC) patients may be
augmented if combined with bevacizumab, a monoclonal antibody to
vascular endothelial growth factor (VEGF) with anti-angiogenetic
activity. Metronomic chemotherapy is a newest approach which employs
cytotoxic drugs at lower doses with very close and regular
administrations, which has shown anti-angiogenetic effects, epigenetic
attenuation of cancer phenotype and immune-modulation. Metronomic
chemotherapy with cisplatinum and oral etoposide (mPE) has been tested
in NSCLC patients with promising results. We have thus investigated a
newest biochemotherapy regimen with mPE + bevacizumab (mPEBev regimen)
in advanced NSCLC patients.
Methods: This is a phase IB/II
trial designed to evaluate toxicity, anti-tumor and biological activity
of bevacizumab given at escalating doses in combination with mPE
chemotherapy. Twenty-six patients with inoperable NSCLC and an ECOG?2
were enrolled in the study and received every 21 days, iv. cisplatinum
(30 mg/sqm, days 1-3), oral etoposide (50 mg/sqm, days 1-15) and
bevacizumab (day 3) at different dose levels (no antibody/control
group; 2.5; 5; 7.5; and 10 mg/kg).
Results: The treatment
resulted very active in those patients who received bevacizumab with a
95% objective response rate (19/20), with a median time to progression
of 7.55 months. There were two early deaths at higher bevacizumab
dosages: one due to a cardiovascular accident (7.5 mg/kg) and another
to lung hemorrhage (10mg/kg). We reported also 4 cases of psychic
depression and 4 cases of pneumonia which evolved into lung cavitation.
A magnetic resonance monitoring showed a significant treatment-related
blood perfusion reduction in the tumor site. It was also observed a
progressive decrease in VEGF, thrombospondin-1 levels which were not
dependent upon bevacizumab dose and were not observed in the controls.
Conclusions: mPEBev
regimen resulted very active in advanced NSCLC patients. Our metronomic
biochemotherapy regimen with lower bevacizumab doses (2.5-5 mg/Kg)
deserves to be investigated in further phase II-III trials.