Continuous Infusion of Cilengitide Plus Chemoradiotherapy for Patients With Stage III Non-Small-cell Lung Cancer: A Phase I Study.

Isabelle Rouquette, Elizabeth Cohen-Jonathan Moyal, Julien Mazières, Etienne Chatelut, Pascale Olivier, Christine Toulas, Jean-Pierre Delord, Muriel Mounier, Carlos Gomez-Roca, Carole Massabeau, Richard Aziza, Lawrence Dierickx, Gavin Plat, Laurence Bigay-Gamé, Anouchka Modesto, Thomas Filleron, Jonathan Khalifa

Journal: Clinical lung cancer 2019;19(3):e277-e285

PMID: 29221762

Full Text on Elsevier Science View on PubMed

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.

Address: Department of Radiation Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.; Department of Radiation Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France. Electronic address: [email protected].; Department of Biostatistics, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.; Department of Pneumology, Centre Hospitalo-Universitaire Larrey, Toulouse, France.; Department of Imaging/Nuclear Medicine, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.; Department of Pathology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.; Department of Medical Oncology, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.; 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.; INSERM U1037, Centre de Recherche Contre le Cancer de Toulouse, Toulouse, France.; Vigilance des Essais Cliniques, de la recherche et de l'innovation du Centre Hospitalier Universitaire de Toulouse, Toulouse, France.; 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.; 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.; 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.

DOI: 10.1016/j.cllc.2017.11.002

Link outs

Free resources

Medical:

https://medlineplus.gov/lungcancer.html

Other Literature Sources:

https://scite.ai/reports/29221762

Subscription / membership required

Full Text Sources:

MeSH Terms: Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Chemoradiotherapy, Cisplatin, Female, Humans, Infusions, Intravenous, Lung Neoplasms, Male, Maximum Tolerated Dose, Middle Aged, Positron Emission Tomography Computed Tomography, Receptors, Vitronectin, Snake Venoms, Vinorelbine