TY - JOUR
T1 - A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer
AU - Marshall, John L.
AU - Eisenberg, Steven G.
AU - Johnson, Michael D.
AU - Hanfelt, John
AU - Dorr, F. Andrew
AU - El-Ashry, Dorraya
AU - Oberst, Michael
AU - Fuxman, Yair
AU - Holmlund, Jon
AU - Malik, Shakun
PY - 2004/11
Y1 - 2004/11
N2 - This phase II study was designed to characterize the clinical activity of ISIS 3521 in patients with metastatic colorectal cancer (CRC). Sixteen patients with pretreated or refractory CRC were treated with ISIS 3521. Eleven patients were dose of 2.0 mg/kg per day, and 5 patients 3.0 mk/kg per day given over 21 days followed by a 7-day rest period. Patients continued with study until evidence of disease progression or unacceptable toxicity was detected. Patients underwent baseline tumor biopsies followed by a second biopsy during the last week of the first 21-day infusion. All 16 patients underwent baseline tumor biopsies, and 12 of the 16 patients underwent on-study tumor biopsies. No evidence of tumor response was observed. One patient had stable disease after 2 cycles and remained on for 1 additional cycle only to demonstrate progression of the disease at that time. No dolse-limiting or other significant toxicities were observed at both dosages, which could not be, explained by progression of disease. Fatigue was common in all patients treated but was dot dose limiting, and there was no evidence of coagulopathy, Analysis of the tumor biopsies obtained from the 11 evaluable samples showed marked uptake of ISIS 3521 in the normal liver parenchyma. However, there was minimal uptake within the tumor cells. In addition, no evidence of any alteration in protein kinase C-α within the tumors or any downstream effect's leading to apoptosis were observed, ISIS 3S21 demonstrated, no clinical activity or target, modulation in refractory metastatic CRC.
AB - This phase II study was designed to characterize the clinical activity of ISIS 3521 in patients with metastatic colorectal cancer (CRC). Sixteen patients with pretreated or refractory CRC were treated with ISIS 3521. Eleven patients were dose of 2.0 mg/kg per day, and 5 patients 3.0 mk/kg per day given over 21 days followed by a 7-day rest period. Patients continued with study until evidence of disease progression or unacceptable toxicity was detected. Patients underwent baseline tumor biopsies followed by a second biopsy during the last week of the first 21-day infusion. All 16 patients underwent baseline tumor biopsies, and 12 of the 16 patients underwent on-study tumor biopsies. No evidence of tumor response was observed. One patient had stable disease after 2 cycles and remained on for 1 additional cycle only to demonstrate progression of the disease at that time. No dolse-limiting or other significant toxicities were observed at both dosages, which could not be, explained by progression of disease. Fatigue was common in all patients treated but was dot dose limiting, and there was no evidence of coagulopathy, Analysis of the tumor biopsies obtained from the 11 evaluable samples showed marked uptake of ISIS 3521 in the normal liver parenchyma. However, there was minimal uptake within the tumor cells. In addition, no evidence of any alteration in protein kinase C-α within the tumors or any downstream effect's leading to apoptosis were observed, ISIS 3S21 demonstrated, no clinical activity or target, modulation in refractory metastatic CRC.
KW - Antisense technology
KW - Apoptosis
KW - Immunohistochemistry
KW - Ki-67
KW - Proliferation-associated nuclear antigen
KW - Protein kinase C
UR - http://www.scopus.com/inward/record.url?scp=19944422076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=19944422076&partnerID=8YFLogxK
U2 - 10.3816/CCC.2004.n.026
DO - 10.3816/CCC.2004.n.026
M3 - Article
C2 - 15555210
AN - SCOPUS:19944422076
SN - 1533-0028
VL - 4
SP - 268
EP - 274
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 4
ER -