A phase II and pharmacological study of the matrix metalloproteinase inhibitor (MMPI) COL-3 in patients with advanced soft tissue sarcomas.
This phase II study evaluated the antitumor activity of the tetracycline analog COL-3, a potent inhibitor of metalloproteinases (MMPs), particularly MMP-2 and MMP-9, on a continuous oral schedule at a dose of 50 mg/m2 daily in patients with advanced and/or metastatic soft tissue sarcoma (STS). The principal endpoints were the rate of objective tumor regression and the proportion of patients who did not experience disease progression during the first 8 weeks of treatment. Other study objectives included an assessment of pharmacology of COL-3, time to progression (TTP), and overall survival. A Simon two-stage design with multinomial stopping rule was employed, with 15 patients enrolled during the first stage of the study. Although COL-3 was generally well-tolerated, there were no objective responses and 5(33%) patients experienced disease progression during the first 8 weeks of treatment, which exceeded the criteria established a priori with regard to pursuing further evaluations of COL-3 in STS. The median values for TTP and survival were 109 and 279 days, respectively. Based on these results, further studies of COL-3 on this administration schedule in patients with STS are not warranted.
Chu
Quincy S C
QS
Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada. quincchu@cancerboard.ab.ca
Forouzesh
Bahram
B
Syed
Samira
S
Mita
Monica
M
Schwartz
Garry
G
Cooper
Joshua
J
Copper
Joshua
J
Curtright
Janet
J
Rowinsky
Eric K
EK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012509:Sarcoma / Q000188:drug therapy* / Q000556:secondary; D013754:Tetracyclines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D013754:Tetracyclines; C117155:tetracycline CMT-3