A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer

John L. Marshall, Steven G. Eisenberg, Michael D. Johnson, John Hanfelt, F. Andrew Dorr, Dorraya El-Ashry, Michael Oberst, Yair Fuxman, Jon Holmlund, Shakun Malik

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)268-274
Number of pages7
JournalClinical Colorectal Cancer
Volume4
Issue number4
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

ISIS 3521
Colorectal Neoplasms
Biopsy
Neoplasms
Disease Progression

Keywords

  • Antisense technology
  • Apoptosis
  • Immunohistochemistry
  • Ki-67
  • Proliferation-associated nuclear antigen
  • Protein kinase C

ASJC Scopus subject areas

  • Oncology

Cite this

Marshall, J. L., Eisenberg, S. G., Johnson, M. D., Hanfelt, J., Dorr, F. A., El-Ashry, D., ... Malik, S. (2004). A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer. Clinical Colorectal Cancer, 4(4), 268-274.

A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer. / Marshall, John L.; Eisenberg, Steven G.; Johnson, Michael D.; Hanfelt, John; Dorr, F. Andrew; El-Ashry, Dorraya; Oberst, Michael; Fuxman, Yair; Holmlund, Jon; Malik, Shakun.

In: Clinical Colorectal Cancer, Vol. 4, No. 4, 01.01.2004, p. 268-274.

Research output: Contribution to journalArticle

Marshall, JL, Eisenberg, SG, Johnson, MD, Hanfelt, J, Dorr, FA, El-Ashry, D, Oberst, M, Fuxman, Y, Holmlund, J & Malik, S 2004, 'A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer', Clinical Colorectal Cancer, vol. 4, no. 4, pp. 268-274.
Marshall JL, Eisenberg SG, Johnson MD, Hanfelt J, Dorr FA, El-Ashry D et al. A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer. Clinical Colorectal Cancer. 2004 Jan 1;4(4):268-274.
Marshall, John L. ; Eisenberg, Steven G. ; Johnson, Michael D. ; Hanfelt, John ; Dorr, F. Andrew ; El-Ashry, Dorraya ; Oberst, Michael ; Fuxman, Yair ; Holmlund, Jon ; Malik, Shakun. / A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer. In: Clinical Colorectal Cancer. 2004 ; Vol. 4, No. 4. pp. 268-274.
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