Antitumor activity of bevacizumab in combination with metronomic chemotherapy (mPEBev regimen) in metastatic non-small cell lung cancer

Background: Bevacizumab, is a humanized monoclonal antibody to vasculo-endothelialgrowth- factor, with anti-cancer activity in nonsmall- cell-lung cancer (NSCLC) patients. Results from a previous dose/finding phase I study in advanced NSCLC patients, described the antiangiogenic and toxicological effects of a newest bevacizumab combination with metronomic chemotherapy with cisplatin and oral etoposide (mPEBev regimen) and identified the bevacizumab dosage to use in future trials. We therefore, designed a phase II trial to evaluate in advanced NSCLC patients the antitumor activity of this metronomic dose/dense regimen. Methods: 45 patients (36 males and 9 females), with a mean age of 54 years, an ECOG 2, stage IIIB/IV and NSCLC (34 adenocarcinoma, 10 squamous cell carcinoma, 1 undifferentiated carcinoma) were enrolled. They received every three weeks, cisplatin (30 mg/sqm, days 1-3), oral etoposide (50 mg, days 1-15) and bevacizumab (5 mg/kg, day 3). Responsive patients received maintenance therapy after 4 chemotherapy cycles with bevacizumab 5mg/kg every 3 weeks and daily erlotinib (150 mg). Kaplan Meier curves were used to estimate survival (OS) and progression free survival (PFS). Results: Grade I-II hematological, mucosal toxicity and alopecia were the most common adverse events. The occurrence of severe infections (17%), thromboembolic episodes (4.4%) and severe mood disturbances (6.7%) were also recorded. There was a partial response in 31 (68.8%) patients, a stabilization in 8 (17.8%), and a progressive disease in 6 (13.3%) with a median PFS of 8.00 (95%CI;6.192-9.808) months and median OS of 15 months (95% 10.660-19.340). Conclusion: Our bio-chemotherapy regimen resulted very active in advanced NSCLC however, the toxicity associated with the treatment will require strict selection of the patients to enroll in future studies.