Carole Massabeau1, Jonathan Khalifa2, Thomas Filleron3, Anouchka Modesto1, Laurence Bigay-Gamé4, Gavin Plat4, Lawrence Dierickx5, Richard Aziza5, Isabelle Rouquette6, Carlos Gomez-Roca7, Muriel Mounier3, Jean-Pierre Delord8, Christine Toulas9, Pascale Olivier10, Etienne Chatelut11, Julien Mazières12, Elizabeth Cohen-Jonathan Moyal13. 1. Department of Radiation Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. 2. Department of Radiation Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. Electronic address: jonathan.khalifa@hotmail.fr. 3. Department of Biostatistics, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. 4. Department of Pneumology, Centre Hospitalo-Universitaire Larrey, Toulouse, France. 5. Department of Imaging/Nuclear Medicine, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. 6. Department of Pathology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. 7. Department of Medical Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. 8. Department of Medical Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France; Université Paul Sabatier, Toulouse, France; INSERM U1037, Centre de Recherche Contre le Cancer de Toulouse, Toulouse, France. 9. INSERM U1037, Centre de Recherche Contre le Cancer de Toulouse, Toulouse, France. 10. Vigilance des Essais Cliniques, de la recherche et de l'innovation du Centre Hospitalier Universitaire de Toulouse, Toulouse, France. 11. Université Paul Sabatier, Toulouse, France; INSERM U1037, Centre de Recherche Contre le Cancer de Toulouse, Toulouse, France; Laboratoire de Pharmacologie, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. 12. Department of Pneumology, Centre Hospitalo-Universitaire Larrey, Toulouse, France; Université Paul Sabatier, Toulouse, France; INSERM U1037, Centre de Recherche Contre le Cancer de Toulouse, Toulouse, France. 13. Department of Radiation Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France; Université Paul Sabatier, Toulouse, France; INSERM U1037, Centre de Recherche Contre le Cancer de Toulouse, Toulouse, France.
Abstract
INTRODUCTION: Because of our previous preclinical results, we conducted a phase I study associating the specific αvβ3/αvβ5 integrin inhibitor cilengitide, given as a continuous infusion, with exclusive chemoradiotherapy for patients with stage III non-small-cell lung cancer. PATIENTS AND METHODS: A standard 3+3 dose escalation design was used. Cilengitide was given as a continuous infusion (dose levels of 12, 18, 27, and 40 mg/h), starting 2 weeks before and continuing for the whole course of chemoradiotherapy (66 Gy combined with platinum/vinorelbine), and then at a dose of 2000 mg twice weekly in association with chemotherapy. 2-Deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography (PET) and computed tomography scans were performed before and after the first 2 weeks of cilengitide administration and then every 3 months. RESULTS: Of the 14 patients included, 11 were evaluable for evaluation of the dose-limiting toxicities (DLTs). One DLT, a tracheobronchial fistula, was reported with the 40 mg/h dose. No relevant adverse events related to cilengitide were observed overall. At the PET evaluation 2 months after chemoradiotherapy, 4 of 9 patients had a complete response and 4 had a partial response. The median progression-free and overall survival was 14.4 months (95% confidence interval [CI], 8.4 to not reached) and 29.4 months (95% CI, 11.73 to not reached), respectively. CONCLUSION: Cilengitide, given continuously with chemoradiotherapy, showed acceptable toxicity and gave encouraging clinical results.
INTRODUCTION: Because of our previous preclinical results, we conducted a phase I study associating the specific αvβ3/αvβ5 integrin inhibitor cilengitide, given as a continuous infusion, with exclusive chemoradiotherapy for patients with stage III non-small-cell lung cancer. PATIENTS AND METHODS: A standard 3+3 dose escalation design was used. Cilengitide was given as a continuous infusion (dose levels of 12, 18, 27, and 40 mg/h), starting 2 weeks before and continuing for the whole course of chemoradiotherapy (66 Gy combined with platinum/vinorelbine), and then at a dose of 2000 mg twice weekly in association with chemotherapy. 2-Deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography (PET) and computed tomography scans were performed before and after the first 2 weeks of cilengitide administration and then every 3 months. RESULTS: Of the 14 patients included, 11 were evaluable for evaluation of the dose-limiting toxicities (DLTs). One DLT, a tracheobronchial fistula, was reported with the 40 mg/h dose. No relevant adverse events related to cilengitide were observed overall. At the PET evaluation 2 months after chemoradiotherapy, 4 of 9 patients had a complete response and 4 had a partial response. The median progression-free and overall survival was 14.4 months (95% confidence interval [CI], 8.4 to not reached) and 29.4 months (95% CI, 11.73 to not reached), respectively. CONCLUSION: Cilengitide, given continuously with chemoradiotherapy, showed acceptable toxicity and gave encouraging clinical results.