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Journal of Clinical Oncology
ASCO Foundation
People Living With Cancer
ASCO MD

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Home > Publications > Abstracts >



Phase I/II clinical trial of oral recombinant human
lactoferrin in the treatment of chemotherapy resistant solid tumors.
Year: 2003 Printable Version
Category: Other Novel Agents
Abstract No: 947
Author(s): T. G. Hayes, G. R. Varadhachary, D. Smith, D.
Hintz, A. Varadhachary, G. Falchook; Baylor College of Medicine and VA Medical
Center, Houston, TX; Agennix, Inc., Houston, TX
Abstract: Recombinant human lactoferrin (rhLF), an
immunomodulatory protein, is in development as a cancer drug. There is extensive
animal data showing inhibition of tumor growth and metastases by lactoferrin.
RhLF appears to be safe and well tolerated, having been administered orally to
over 160 patients/subjects without a drug-related serious adverse event. We are
evaluating the safety and efficacy of rhLF in patients with solid tumors that
failed chemotherapy. 33 evaluable patients are receiving open label rhLF in two
14-day cycles separated by a 2-week gap. The first nine patients receive rhLF
doses (1.5, 4.5 and 9 g/day) in cohorts of 3 to establish safety, with the rest
randomized between the two highest doses. We are also evaluating 8-week and
16-week radiological tumor response, tumor markers, and biological markers of
rhLF activity, including increases in circulating CD40+ cells and
immunomodulatory cytokines. We have enrolled seven patients; five have completed
both cycles without a dose limiting toxicity. While no clinical or radiological
tumor response has been observed so far, serum CEA levels in both colon cancer
patients stabilized after rising in the preceding months. We also observed an
immunostimulatory effect in all patients - increases in CD40+ and decreases in
Annexin V staining in peripheral blood cells. Annexin V is an apoptotic marker
whose decrease is associated with enhanced survival of circulating immune cells.
CD40+ antigen-presenting cells are critical to development of a tumor specific
T-cell response. We are encouraged by seeing tumor marker stabilization and
immunostimulation in low dose cohort patients by a novel and well-tolerated oral
drug. Results from the high dose patients will be presented at the meeting.


CD40+/Annexin-
Annexin+/CD40-


(Healthy CD40)
(Pro-Apoptotic Cells)

Baseline (n=5)
1.3%
73.0%

Week 3 (n=6)*
6.1%
39.7%

Week 7 (n=4)**
26.8%
7.3%





Change in Week 7
20-fold Increase
90% Decrease

P-value (1-tailed)
0.0317
<0.0001

* After Cycle 1 ** After Cycle 2






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