Abstract:
: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 given a dose of 2.0 mg/kg per day, and 5 patients received 3.0 mg/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 disease at that time. No dose-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 not 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-a within the tumors or any downstream effects leading to apoptosis were observed. ISIS 3521 demonstrated no clinical activity or target modulation in refractory metastatic CRC.
journal_name
Clin Colorectal Cancerjournal_title
Clinical colorectal cancerauthors
Marshall JL,Eisenberg SG,Johnson MD,Hanfelt J,Dorr FA,El-Ashry D,Oberst M,Fuxman Y,Holmlund J,Malik Sdoi
10.3816/ccc.2004.n.026keywords:
subject
Has Abstractpub_date
2004-11-01 00:00:00pages
268-74issue
4eissn
1533-0028issn
1938-0674pii
S1533-0028(11)70127-Xjournal_volume
4pub_type
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pub_type: 临床试验,杂志文章
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