Author of

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10829

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    P1.11-028 - <b>Antitumor and immune-biological activity of a new metronomic chemotherapy with fractioned cisplatin and oral etoposide combined with bevacizumab (mPEBev) followed by erlotinib maintenance in non small cell lung cancer (NSCLC) patients</b> (ID 2120)

    09:30 - 09:30  |  Author(s): P. Correale
    • Abstract

    Background
    We recently, concluded a phase II trial (mPEBev trial) aimed to evaluate in metastatic non-small-cell-lung-cancer patients (NSCLC), the toxicity and biological and anti-tumour activity of a newest bio-chemotherapy strategy combining metronomic chemotherapy with fractioned cisplatin, oral etoposide with bevacizumab, an anti-vasculo-endothelial-growth-factor (VEGF) monoclonal antibody. All responsive patients had to continue the treatment with a TKI inhibitor (Erlotinib) until disease progression. The treatment resulted safe and very active with effective anti-angiogenic effects (Correale P, 2011 12(2):112). By considering that this treatment strategy was designed on preclinical results suggesting additive interaction of metronomic chemotherapy with VEGF deprivation and EGFR inhibition, in term of anti-tumor/anti-angiogenic-activity and immune-modulation, we investigated in this patients' population the ability of our treatment to generate immune-biological effects with potential antitumor activity.

    Methods
    The mPEBev Phase II trial was approved by the Ethical committee of Siena University. All the enrolled patients signed and informant consent. Thirty-five inoperable NSCLC patients (25 males and 10 females) with an ECOG < 1, and median age of 68 years (range 3-75) were enrolled. Twenty-six had an adeno-carcinoma, 6 a squamocellular and 3 NAS carcinoma. All patients received cisplatin (30mg/sqm days 1-3q21 etoposide 50mg/sqm days 1-15/21 and bevacizumab 5mg/kg on the day 3q21). After four treatment courses, all patients who achieved a partial response (PR) or a stable disease (SD) received daily Erlotinib (150 mg/day), starting one week after the end of chemotherapy until disease progression (PD). A cytokine multiplex analysis and an immune-cytofluorimetric analysis was performed on blood samples isolated at the baseline, after 4 bio-chemotherapy courses and 3 months after the end of bio-chemotherapy. Statistical significance (p <0.05) was searched between by comparing the results obtained on the samples taken at baseline and treatment timing as described above.

    Results
    Our biological multiplex analysis revealed a significant decrease in serum levels of VEGF (68,9 +/-23 vs. 30+/-12 ng/ml), and interleukin (IL)-10 (326 +/-136 vs. 187,6 +/-60 ng/ml) which was maintained along TKI treatment. There was no change in angiopoietin, interferon gamma, IL-12, PECAM and follistatin levels. During TKI maintenance we additionally, recorded an increase in IL-8 (59,2 +/-11 vs. 165,15 +/- 38 ng/ml), and leptine (7275+/- 2202 vs. 11078 +/- 4280 ng/ml) associated with a significant decrease in G-CSF levels (94,3 +/-59 vs. 17,61 +/-3 ng/ml) and angiopoietin levels (1099,9 +/- 123 vs. 603 +/-162 ng/ml). Our immune-cytofluorimetric analysis of patients’ PBMCs showed a significant treatment-related increase in activated (CD3[-]CD11C[+]CD14[+]CD80[+]CD83[+]) dendritic cells [4.3+/-1.5 vs. 8.5+/-2,1%] and activated (CD3[+]CD8[+]CD62L[+]) cytotoxic-T -lymphocytes [2.5 +/-1,2 vs. 5,5 +/-0,259%)].

    Conclusion
    Our results suggest that this treatment strategy is safe and active in NSCLC patients, and is able to affects their systemic inflammatory status also inducing immune-modulation with potential antitumor.