Phase I Study of Sunitinib and Erlotinib in Advanced Nonsquamous Non-small Cell Lung Cancer

• Published in: Journal of thoracic oncology 2011-05, Vol.6 (5), p.951-953
• Main Authors: O'Mahar, Shannon E., Campbell, Toby C., Hoang, Tien, Seo, Songwon, Kim, KyungMann, Larson, Martha M., Marcotte, Sarah M., LoConte, Noelle K., Traynor, Anne M.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Epidermal growth factor receptor; Erlotinib Hydrochloride; Female; Humans; Indoles - administration & dosage; Lung Neoplasms - drug therapy; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Non-small cell lung cancer; Phase I clinical trial; Pyrroles - administration & dosage; Quinazolines - administration & dosage; Receptor protein-tyrosine kinases; Sunitinib; Survival Rate; Treatment Outcome; Vascular endothelial growth factor receptors
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0b013e31820db227

Erlotinib has prolonged survival in unselected patients with advanced non-small cell lung cancer, whereas sunitinib has yielded promising rates of disease control in previously treated patients. We conducted a dose escalation study of this combination to determine the maximum tolerated dose of sunitinib in combination with a fixed dose of erlotinib and to evaluate the toxicities of this combination. Patients with advanced nonsquamous non-small cell lung cancer were treated at two dose levels: sunitinib at either 25 mg or 37.5 mg, with erlotinib 150 mg. Both drugs were given once daily, continuously. Eleven patients enrolled from November 2007 to October 2009. No dose-limiting toxicities occurred. Grade 3/4 adverse events at least possibly related to treatment were seen in seven patients (64%). Six patients (54%) required dose modifications, and three (27%) discontinued study treatment due to toxicity. Rates of grade 3 diarrhea and mucositis exceeded those seen with single-agent erlotinib or sunitinib. One patient (9%) attained a partial response lasting 16.3 months. Although no dose-limiting toxicities occurred, it is difficult to recommend erlotinib 150 mg and sunitinib 37.5 mg daily as the phase II dose for this combination due to the high rate of adverse events. Because of the overlapping toxicity profile of each agent, this combination was poorly tolerated in our population.