1208P - Continuous infusion of cilengitide with radio-chemotherapy in Stage III NSCLC: a phase I study

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Locally Advanced
Surgery and/or Radiotherapy of Cancer
Presenter Elizabeth Cohen-Jonathan Moyal
Citation Annals of Oncology (2014) 25 (suppl_4): iv417-iv425. 10.1093/annonc/mdu348
Authors E.L. Cohen-Jonathan Moyal1, C. Massabeau1, T. Filleron1, A. Modesto1, J. Bachaud1, I. Rouquette2, L. Dierickx3, R. Aziza3, L. Bigay-Gamé4, G. Plat2, M. Mounier5, C.A. Gomez-Roca6, J. Delord6, J. Mazières7
  • 1Dpt De Radiotherapie, Institut Universitaire du Cancer-Oncopole, 31059 - Toulouse/FR
  • 2Thoracic Oncology, CHU Toulouse - Hôpital Larrey, 31000 - toulouse/FR
  • 3Dpt D'imagerie, Institut Universitaire du Cancer-Oncopole, 31059 - Toulouse/FR
  • 4Unité D'oncologie Thoracique, Larrey hospital, 31059 - Toulouse/FR
  • 5Bureau Des Essais Cliniques, Institut Universitaire du Cancer-Oncopole, 31059 - Toulouse/FR
  • 6Medical Oncology Dpt, Institut Universitaire du Cancer-Oncopole, 31059 - Toulouse/FR
  • 7Department Of Thoracic Oncology, Hôpital De Larrey, Toulouse/FR

Abstract

Aim

We have shown that αvß3 integrins control radioresistance, hypoxia and angiogenesis and that co-expression of FGF-2 and αvß3 integrins in the tumors of patients treated with exclusive radio-chemotherapy for stage III non-small lung carcinoma (NSCLC), was associated with a worse local control, suggesting that inhibition of αvß3 integrin could induce a radiosensitization of such tumours. We designed a phase I trial associating the specific αvß3/αvß5 integrin inhibitor cilengitide with radio-chemotherapy in patients with stage III NSCLC.

Methods

A standard 3 + 3 dose escalation design was used. Cilengitide was given in continuous infusion starting 2 weeks before and then during the whole course of the radio-chemotherapy (66 Gy combined with a Platine-Navelbine regimen), and then at a dose of 2000 mg twice a week in association with chemotherapy. Planed Cilengitide continuous infusion dose levels were 12, 18, 27 and 40 mg/h. PET-FDG and CT scan were performed before and then after the first two weeks of Cilengitide administration and then 2 months after the end of radio-chemotherapy. Patients were followed by CT scan. Toxicity for DLT was assessed during combined treatment and until 1 month after. Clinical response on CT scan and TEP was evaluated according to RECIST and PERCIST criteria.

Results

Fourteen patients were included between March 2010 and July 2013. Eleven patients were evaluable for DLT. No DLT was observed at level 0, 1 and 2. One DLT, a tracheo-bronchial fistula was reported at the 40 mg/h dose. No relevant adverse event related to Cilengitide (7 grade 1 and one grade 2) was observed on the whole population. Among 11 patients evaluable for efficacy, 9 patients presented a partial response and 2 a stable disease. At 6 months after the end of radio-chemotherapy, 2 patients presented a progressive disease. At PET evaluation 2 months after radio-chemotherapy, 4 patients had a complete response and 4 patients had a partial response.

Conclusions

Cilengitide given continuously with radio-chemotherapy was well tolerated and shows encouraging clinical results, suggesting that targeting αvß3 integrin continuously during radio-chemotherapy in NSCLC is a promising approach to treat this disease.

Disclosure

E.L. Cohen-Jonathan Moyal: E Moyal has been member of an advisory board for Merck KGaA and received a funding grant from Merck KGaA for research. All other authors have declared no conflicts of interest.