TY - JOUR
T1 - Phase II trial of carboxyamidotriazole in patients with relapsed epithelial ovarian cancer
AU - Hussain, Mahrukh M.
AU - Kotz, Herbert
AU - Minasian, Lori
AU - Premkumar, Ahalya
AU - Sarosy, Gisele
AU - Reed, Eddie
AU - Zhai, Suoping
AU - Steinberg, Seth M.
AU - Raggio, Miranda
AU - Oliver, Vyta Kulpa
AU - Figg, William D.
AU - Kohn, Elise C.
PY - 2003/12/1
Y1 - 2003/12/1
N2 - Purpose: Carboxyamidotriazole (CAI) is a cytostatic inhibitor of nonvoltage-operated calcium channels and calcium channel-mediated signaling pathways. It inhibits angiogenesis, tumor growth, invasion, and metastasis. We hypothesized that CAI would promote disease stabilization lasting ≥ 6 months in patients with relapsed ovarian cancer. Patients and Methods: Patients with epithelial ovarian cancer, good end-organ function, measurable disease, and three or fewer prior regimens were eligible. Oral CAI was given daily using a pharmacokinetic-dosing approach to maintain plasma concentrations between 2 and 4 μg/mL. Radiographic imaging to assess response was performed every 8 weeks. Positive outcome included stabilization or improvement of disease lasting ≥ 6 months. Plasma vascular endothelial growth factor (VEGF), interleukin (IL)-8, and matrix metalloproteinase (MMP)-2 were measured. Results: Thirty-six patients were assessable for primary end point analysis, and 38 were assessable for toxicity. Forty-four percent of patients had three prior regimens, more than 50% had four or more disease sites, and 48% had liver metastases. Thirty-three patients reached the targeted concentration range during the first cycle. Eleven patients (31%) attained the ≥ 6-month outcome end point, with one partial response (8 months) and three minor responses (8, 12+, and 13 months). Median time to progression was 3.6 months (range, 1.6 to 13.3 months). CAI was well tolerated, with mostly grade 1 to 2 toxicity. Grade 3 events included fatigue (5%), vomiting (2%), neutropenic fever (2%), and neutropenia (2%). There were no grade 4 adverse events. No associations between VEGF, IL-8, and MMP-2 with CAI concentration or clinical outcome were observed. Conclusion: CAI is a potential agent for additional study in the stabilization of relapsed ovarian cancer. Given a limited toxicity profile, it may have utility as a maintenance therapeutic agent for this disease.
AB - Purpose: Carboxyamidotriazole (CAI) is a cytostatic inhibitor of nonvoltage-operated calcium channels and calcium channel-mediated signaling pathways. It inhibits angiogenesis, tumor growth, invasion, and metastasis. We hypothesized that CAI would promote disease stabilization lasting ≥ 6 months in patients with relapsed ovarian cancer. Patients and Methods: Patients with epithelial ovarian cancer, good end-organ function, measurable disease, and three or fewer prior regimens were eligible. Oral CAI was given daily using a pharmacokinetic-dosing approach to maintain plasma concentrations between 2 and 4 μg/mL. Radiographic imaging to assess response was performed every 8 weeks. Positive outcome included stabilization or improvement of disease lasting ≥ 6 months. Plasma vascular endothelial growth factor (VEGF), interleukin (IL)-8, and matrix metalloproteinase (MMP)-2 were measured. Results: Thirty-six patients were assessable for primary end point analysis, and 38 were assessable for toxicity. Forty-four percent of patients had three prior regimens, more than 50% had four or more disease sites, and 48% had liver metastases. Thirty-three patients reached the targeted concentration range during the first cycle. Eleven patients (31%) attained the ≥ 6-month outcome end point, with one partial response (8 months) and three minor responses (8, 12+, and 13 months). Median time to progression was 3.6 months (range, 1.6 to 13.3 months). CAI was well tolerated, with mostly grade 1 to 2 toxicity. Grade 3 events included fatigue (5%), vomiting (2%), neutropenic fever (2%), and neutropenia (2%). There were no grade 4 adverse events. No associations between VEGF, IL-8, and MMP-2 with CAI concentration or clinical outcome were observed. Conclusion: CAI is a potential agent for additional study in the stabilization of relapsed ovarian cancer. Given a limited toxicity profile, it may have utility as a maintenance therapeutic agent for this disease.
UR - http://www.scopus.com/inward/record.url?scp=0642307226&partnerID=8YFLogxK
U2 - 10.1200/JCO.2003.04.136
DO - 10.1200/JCO.2003.04.136
M3 - Article
C2 - 14645425
AN - SCOPUS:0642307226
SN - 0732-183X
VL - 21
SP - 4356
EP - 4363
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 23
ER -