Multicenter Phase II Study of the Oral MEK Inhibitor, CI-1040, in Patients With Advanced Non-Small-Cell Lung, Breast, Colon, and Pancreatic Cancer

• Published in: Journal of clinical oncology Vol. 22; no. 22; pp. 4456 - 4462
• Main Authors: RINEHART, John, ADJEI, Alex A, GULYAS, Stephen, MITCHELL, David Y, HERRERA, Roman, SEBOLT-LEOPOLD, Judith S, MEYER, Mark B, LORUSSO, Patricia M, WATERHOUSE, David, HECHT, J. Randolph, NATALE, Ronald B, HAMID, Oday, VARTERASIAN, Mary, ASBURY, Peggy, KALDJIAN, Eric P
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15-11-2004; Lippincott Williams & Wilkins
• Subjects: Administration, Oral; Aged; Benzamides - administration & dosage; Benzamides - adverse effects; Benzamides - pharmacology; Benzamides - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Carcinoma, Non-Small-Cell Lung - drug therapy; Colonic Neoplasms - drug therapy; Female; Humans; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; Pancreatic Neoplasms - drug therapy; Pneumology; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Human; Lung disease; Respiratory disease; Multicenter study; Lung cancer; Oral administration; Breast cancer; Malignant tumor; Bronchopulmonary malignant tumor; Colonic disease; Mammary gland diseases; Cancerology; Treatment; Colon cancer; Phase II trial; Digestive diseases; Bronchus disease; Intestinal disease; Advanced stage; Inhibitor; Pancreatic disease
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2004.01.185

This multicenter, open-label, phase II study was undertaken to assess the antitumor activity and safety of the oral mitogen-activated extracellular signal regulated kinase kinase (MEK) inhibitor, CI-1040, in breast cancer, colon cancer, non-small-cell lung cancer (NSCLC), and pancreatic cancer.
Patients with advanced colorectal, NSCLC, breast, or pancreatic cancer received oral CI-1040 continuously at 800 mg bid. All patients had measurable disease at baseline, a performance status of 2 or less, and adequate bone marrow, liver, and renal function. Expression of pERK, pAkt, and Ki-67 was assessed in archived tumor specimens by quantitative immunohistochemistry.
Sixty-seven patients with breast (n = 14), colon (n = 20), NSCLC (n = 18), and pancreatic (n = 15) cancer received a total of 194 courses of treatment (median, 2.0 courses; range, one to 14 courses). No complete or partial responses were observed. Stable disease (SD) lasting a median of 4.4 months (range, 4 to 18 months) was confirmed in eight patients (one breast, two colon, two pancreas, and three NSCLC patients). Treatment was well tolerated, with 81% of patients experiencing toxicities of grade 2 or less severity. Most common toxicities included diarrhea, nausea, asthenia, and rash. A mild association (P < .055) between baseline pERK expression in archived tumor specimens and SD was observed.
CI-1040 was generally well tolerated but demonstrated insufficient antitumor activity to warrant further development in the four tumors tested. PD 0325901, a second generation MEK inhibitor, has recently entered clinical development and, with significantly improved pharmacologic and pharmaceutical properties compared with CI-1040, it may better test the therapeutic potential of MEK inhibition in cancer.